Excess Functions Research Articles

Study on the Effect of Bridge Deck Spacing on Characteristics of Smoke Temperature Field in a Bridge Fire

The numerical simulation method is used to simulate the distribution characteristics of the smoke temperature field of a double-deck bridge smoke temperature field during tanker fire under natural ventilation. The influence of the distance between double decks on the truss and ceiling temperature field change in the double-deck bridge is investigated. The results show that the range of high-temperature area gradually decreases with the increase in bridge deck spacing. The maximum excess temperature function of the tunnel ceiling is also applicable to the bridge, but the coefficient is smaller than that of the tunnel experimental formula. An equation is proposed to predict the maximum excess temperature of the truss under different bridge deck spacings. As the bridge deck spacing increases, the maximum excess temperature decreases. The excess temperature of the truss increases along the truss, and the maximum excess temperature appears at the top of the truss. Based on the energy equation, an equation for the excess temperature of the truss is established. As the vertical height increases, the excess temperature of the truss above the fire source exponentially increases. The research results will contribute to the fire hazard evaluation and safety design of bridges.

Thermal, optical, and volumetric studies on mixing properties of binary nematic mixtures of 9CHBT/11CHBT

• Phase diagrams of a series of binary nematic mixtures (9CHBT/11CHBT) were studied by DSC method. • The modified four-parameter model was used by fitting the experimental data. • The temperature dependence of refractive indices, birefringence and order parameters in nematic phase was investigated. • Quantum chemical calculations on the nematogens provide supportive picture of the optical measurements. Phase diagrams and optical properties of a series of nematic binary mixtures composed of 4-(trans-4′-n-nonylcyclohexyl) isothiocyanatobenzen (9CHBT) and 4-(trans-4′-n-undecylcyclohexyl) isothiocyanatobenzen (11CHBT) were established in the entire range of molar fraction by differential scanning calorimetry method, refractometry as well as density measurements. In this research the thermodynamic, optical, and volumetric properties of the eutectic mixture ( E 9 , 11 ) composed of 9CHBT and 11CHBT ( x 11 C H B T = 0.4 ) were studied and interpreted. The binary phase diagram is in comparable with that predicted from Schroder–van Laar equation. The excess functions were determined using the calculated activity coefficients of the eutectic mixture. Moreover, the temperature dependence of refractive indices, birefringence, and order parameters of the pure nematogens and the binary eutectic mixture was investigated. In contrast to the individual nematogens, the eutectic mixture ( E 9 , 11 ) displays a crossover temperature ( T CO ) based on the four-parameter model. Finally, results from quantum chemical calculations on the studied nematogens provide an overall supportive and coherent picture of the thermal, optical measurements. All calculations were performed using the Turbomole software package. The used methodology allows for an acceptable approximation of effective polarizabilities.

Outage Probability Due to PDL Using Threshold Exceedances: Implications of DD-LMS Equalization and Inter-Channel Fiber Nonlinearities

The outage probability due to polarization dependent loss (PDL) is estimated using the method of threshold exceedances for a multi-channel transmission model that includes i) decision-directed least-mean-square equalization to partially compensate PDL, ii) the dominant fiber nonlinear effects of cross-phase modulation and cross-polarization modulation, and iii) transceiver noise. The outage probability is defined in terms of the bit-wise achievable information rate (BW-AIR) being less than a threshold value for the generalized mutual information determined by the forward error correcting code rate. The root mean square error between the mean excess function and a theoretical fit to it is used for the critical step of determining the threshold below which the BW-AIR data is represented by the generalized Pareto distribution. The applicability of the method of threshold exceedances is demonstrated for 32 Gbaud, dual-polarization 64-ary quadrature amplitude modulation with a uniform constellation.

Excess thermodynamic functions of phosphonium-based deep eutectic solvent for various organic solutes at different temperatures

BackgroundDeep eutectic solvents have presented excellent properties and have been utilized in various research areas of chemistry. These solvents have recently been reported as one of the most fascinating with promising possibilities when compared to the other solvents. MethodIn this present study, the limiting activity coefficients have been estimated for 32 various volatile organic solutes (aliphatic and aromatic hydrocarbons, alcohols, THF, thiophene, acetonitrile, ketones) and water in [trihexyltetradecylphosphonium decanoate + ethylene glycol] prepared at 1: 4 molar ratio, respectively. Measurements were conducted at different temperatures, T = (313.15–343.15) K and at atmospheric pressure. Gas liquid chromatography coupled with thermal conductivity detector was employed to obtain the experimental retention data of solutes in the deep eutectic solvent. The partial molar excess properties, such as enthalpies, entropies, and Gibbs energies were determined at infinite dilution from the calculated limiting activity coefficients. In addition, the selectivity and capacity values for the separation problems such as (acetone/ethanol, cyclohexane/benzene, benzene/toluene, and butanol/MEK) were determined from the limiting activity coefficients. FindingsThe attained values proved that trihexyltetradecylphosphonium decanoate + ethylene glycol deep eutectic solvent could be utilized in the separation of azeotropes. The results were discussed based on the intermolecular interactions occurring in the deep eutectic solvent mixtures. The influence of the hydrogen bond donor on deep eutectic solvent behavior was discussed.

The role of microglial/macrophagic salt-inducible kinase 3 on normal and excessive phagocytosis after transient focal cerebral ischemia

Previous studies suggested that anti-inflammatory microglia/macrophages (Mi/MΦ) play a role in “normal phagocytosis,” which promoted the rapid clearance of necrotic substances and apoptotic cells. More recently, a few studies have found that Mi/MΦ also play a role in “pathological phagocytosis” in the form of excessive or reduced phagocytosis, thereby worsening damage induced by CNS diseases. However, the underlying mechanisms and the Mi/MΦ subtypes related to this pathological phagocytosis are still unknown. Salt-inducible kinase 3 (SIK3), a member of the 5’ adenosine monophosphate-activated protein kinase (AMPK) family, has been shown to regulate inflammation in several peripheral diseases. Whether SIK3 also regulates the inflammatory response in CNS diseases is currently unknown. Therefore, in this study, we created a transgenic tamoxifen-induced Mi/MΦ-specific SIK3 conditional knockout (SIK3-cKO) mouse to examine SIK3’s role in phagocytotic function induced by transient focal cerebral ischemia (tFCI). By single-cell RNA-seq, we found the pro-inflammatory Mi/MΦ phenotype performed an excessive phagocytotic function, but the anti-inflammatory Mi/MΦ phenotype performed a normal phagocytotic function. We found that SIK3-cKO caused Mi/MΦ heterogenization from the transitional phenotype to the anti-inflammatory phenotype after tFCI. This phenotypic shift corresponded with enhanced phagocytosis of both apoptotic and live neurons. Interestingly, SIK3-cKO enhanced normal phagocytosis of myelin debris but attenuating excessive phagocytosis of non-damaged myelin sheath, thereby protecting white matter integrity after tFCI. CD16, a pro-inflammation marker, was decreased significantly by SIK3-cKO and correlated with “excessive phagocytosis.” SIK3-cKO promoted long-term recovery of white matter function and neurological function as assessed with electrophysiological compound action potential (CAPs) and behavioral analysis. This study is the first to show a role of SIK3 in Mi/MΦ phagocytosis in CNS diseases, and reveals that promoting Mi/MΦ anti-inflammatory heterogenization inhibits “excessive phagocytosis” of live cells and facilitates “normal phagocytosis” of apoptotic cells. Therefore, inhibition of SIK3 in Mi/MΦ may be a potential therapeutic target in stroke and other CNS diseases with accompanying white matter destruction.Graphical abstractIn the acute stage of tFCI, Mi/MΦ polarized into different phenotypes. The pro-inflammatory Mi/MΦ phenotype performed an excessive phagocytotic function. In contrast, the anti-inflammatory Mi/MΦ phenotype performed a normal phagocytotic function. After tFCI, SIK3-cKO promoted anti-inflammatory phenotypic heterogenization of Mi/MΦ. SIK3-cKO promoted Mi/MΦ phagocytosis of apoptotic (normal phagocytosis) and living neuronal cell bodies (excessive phagocytosis) in gray matter. Interestingly, SIK3-cKO specifically increased normal phagocytosis of myelin debris concurrent with an attenuation of excessive phagocytosis of myelin sheath in white matter. These changes induced by SIK3-cKO were associated with protection of white matter integrity and long-term neurofunctional recovery after tFCI.

Surface and Calorimetric Behavior of N,N-Dimethylacetamide with n-Alkanols or 2-Alkanols

The surface tension at the liquid–air interface of eight binary mixtures formed by N,N-dimethylacetamide and n-alkanols (from methanol to 1-pentanol) or 2-alkanols (from 2-propanol to 2-pentanol) was studied at three different temperatures (283.15, 298.15, and 313.15 K) and a pressure of 0.1 MPa. Surface tension deviations were also calculated. Moreover, the excess molar enthalpies for all of these mixtures were measured at T = 298.15 K and a pressure of 0.1 MPa. Both deviation and excess functions were correlated with the mole fraction by means of the Redlich–Kister equation. The surface tension deviations are found to be positive for the system containing methanol, sigmoidal for ethanol and negative for the rest of the alkanols. With regard to excess molar enthalpies, negative values are found for the system containing methanol, sigmoidal values for ethanol, and positive values for the rest of the alkanols.

Sulfated Glucuronorhamnoxylan from Capsosiphon fulvescens Ameliorates Osteoporotic Bone Resorption via Inhibition of Osteoclastic Cell Differentiation and Function In Vitro and In Vivo.

Excessive osteoclast differentiation and/or bone resorptive function causes a gradual loss of bone, leading to the pathogenesis of bone diseases such as osteoporosis (OP). In this study, a sulfated glucuronorhamnoxylan polysaccharide (designated SPS-CF) of the green alga Capsosiphon fulvescens was evaluated for anti-osteoporotic activity using osteoclastic cells differentiated from RAW264.7 macrophages by receptor activator of NF-κB ligand (RANKL) treatment and ovariectomized (OVX) female mice as a postmenopausal OP model. With negligible cytotoxicity, SPS-CF (50μg/mL) significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity, actin ring formation, and expression of matrix metalloproteinase 9 (MMP-9), cathepsin K, TRAF6, p-Pyk2, c-Cbl, c-Src, gelsolin, carbonic anhydrase II (CA II), and integrin β3, indicating that SPS-CF inhibits the differentiation and bone resorptive function of osteoclasts. Removal of sulfate groups from SPS-CF abolished its anti-osteoclastogenic activities, demonstrating that sulfate groups are critical for its activity. Oral administration of SPS-CF (400mg/kg/day) to OVX mice significantly augmented the bone mineral density (BMD) and serum osteoprotegerin (OPG)/RANKL ratio. These results demonstrated that SPS-CF exerts significant anti-osteoporotic activity by dampening osteoclastogenesis and bone resorption via downregulation of TRAF6-c-Src-Pyk2-c-Cbl-gelsolin signaling and augmentation of serum OPG/RANKL ratios in OVX mice, suggesting that SPS-CF can be a novel anti-osteoporotic compound for treating postmenopausal OP.

Walrasian equilibrium without homogeneity and Walras’ Law

This paper introduces two new boundary conditions that ensure the existence of a Walrasian equilibrium in monetary economies violating Walras’ Law and homogeneity of degree zero of the excess demand function. The two conditions are more general than those adopted by the existing literature. The existence of a Walrasian equilibrium with free disposal is also considered. As a by-product of our analysis, a refinement of the celebrated Uzawa’s equivalence Theorem and extensions of the Hartman–Stampacchia and Poincaré–Miranda Theorems are also provided.

Pyrrolidinium bromide deep eutectic solvents in separation of molecular solutes: Solvent selection for separating industrial mixtures

The separation of molecular solutes utilizing deep eutectic solvents for industrial processes is essential and important for the purpose of green solvent applications. Deep eutectic solvents (DES) based on 1.000:2.002 M ratio of [1-ethyl-1-methylpyrrolidinium bromide + triethylene glycol] and 1.000:2.001 M ratio of [1-ethyl-1-methylpyrrolidinium bromide + diethylene glycol] were used to evaluate their potential in separation of industrial mixtures. The pre-screening of the prepared DESs was based on the activity coefficients at infinite dilution measurements using gas liquid chromatography at different temperatures and at atmospheric pressure. The experimental data was conducted at temperature, T = (313.15–343.15) K. The intermolecular interactions occurring between the solvent and solute were discussed. These were further discussed by computing the excess thermodynamic functions at infinite dilution (enthalpies, ΔH1E,∞, Gibbs free energies, ΔG1E,∞, and entropy term, TrefΔS1E,∞). The effectiveness of the investigated deep eutectic solvents was based on the separation parameters (selectivities and capacity) values. These extraction parameters give a clear indication on how much of solvent would be required for a specific extraction and how selective the solvent is towards solutes to be separated. The results also reveal the ability of the investigated deep eutectic solvents to dissolve the solutes. The investigated deep eutectic solvents (DESs) were found to be useful in separating mixtures comprising (alkane-alcohol and acetone-ethanol). The influence of percentage loading, molar ratio as well as the influence of hydrogen bond donor was discussed.

Thermodynamic excess functions in organic ternary mixture ‐ Statistical approach (Cibulka expansion)

AbstractAcoustic velocity (U), viscosity (η), and density (ρ) characteristics were conducted for different ternary blends of aniline + toluene mixed with some 1‐alcohols at 303 K. Acoustical quantities such as adiabatic compressibility (β), free length (Lf), free volume (Vf), and internal pressure (πi) are acquired from the obtained results for all the blends, with a perspective to study the nature of molecular interaction. These parameters were analyzed along with their excess values (AE) and are found to be useful in evaluating the strength and magnitude of interaction in the blends. The measurement reveals that the interaction between the aniline‐alcohol complexes predominant the other interaction. The excess parameters are fitted to polynomial‐kind Cibulka formula and the coefficient of the fitting are found to be corroborate this work.

Resistances to Educational Change: Teachers’ Perceptions

Educational changes require a great effort on the part of the entire educational community and, above all, the active involvement of teachers. The aim of this article was to analyze the main resistances to change that predominate among teachers at different educational stages. Through a non-experimental design, using an online questionnaire, teachers’ beliefs about factors influencing resistance to change were collected. The results indicate that the participants do not have great resistance to educational change and that legislative changes and the perception of teachers as having excessive functions are the most common aspects of resistance. There is greater resistance to change among men and in public schools and as the experience and age of the teaching staff increases. Based on the results, it is suggested that the educational center be placed as the unit of change, increasing the leadership of the director to carry out the changes suggested by the center itself, fostering teamwork among teachers, and institutionally supporting innovative initiatives that are evaluated or facilitating teacher training in relation to their teaching practice.

Outbreak of Silicosis in Workers Producing Artificial Stone Skirting Boards: A Novel Application of Silica-Based Composites

Outbreak of Silicosis in Workers Producing Artificial Stone Skirting Boards: A Novel Application of Silica-Based Composites

α-Linolenic acid rich-chia seed modulates visceral adipose tissue collagen deposition, lipolytic enzymes expression, insulin signaling and GLUT-4 levels in a diet-induced adiposity rodent model

Given obesity and its associated metabolic disorders have reached epidemic proportions, the study of therapeutic strategies targeting white adipose tissue (WAT) are of main research interest. We previously shown that α-linolenic acid–rich chia seed was able to ameliorate a wide range of metabolic disorders including body fat accretion in sucrose-rich diet (SRD)-fed rats, an experimental model of visceral adiposity and insulin resistance. However, the mechanisms involved are not fully clarified. The aim of this study was to evaluate the effect of chia seed administration upon WAT remodeling and key enzymes that controls lipolysis, insulin signaling (tAKT, pAKT), and GLUT-4 levels in different visceral fat pad depots (epididymal –eWAT- and retroperitoneal –rWAT- adipose tissues) of SRD-fed rats. Results showed that chia seed reduces adipocytes hypertrophy, the increased lipid content and collagen deposition in both WAT. These changes were accompanied by a significant reduction of HSL and ATGL protein levels in eWAT and HSL protein levels in rWAT. Moreover, chia seed restored the altered expression pattern of the pAKT observed in SRD-fed rats, and modulated GLUT-4 levels. Chia seed could be a dietary intervention of great relevance with potential beneficial effects in the management of body fat excess and WAT function.

Study of short range and long range molecular interactions in binary liquid mixtures of N,N-dimethylformamide (DMF) and 1-propanol

In the present study precisely measured properties; static dielectric constant (ε0), refractive index (n) and density (ρ) of binary liquid mixtures of N,N-dimethylformamide (DMF) and 1-propanol (1-PN) have been used to determine linear correlation parameter (grr), mutual linear correlation parameter (gAB), excess Helmholtz free energy functions (ΔF) and excess molar polarization (ΔP). The dipolar contributions to these functions arising from long range electrostatic interaction, short range interaction between identical molecules and short range interaction between dissimilar molecules have been assessed separately. The excess thermodynamic functions calculated from the experimental data supports the formation of clusters with antiparallel or destructive angular correlation (β-clusters). The variation of excess static dielectric constant, excess refractive index and excess molar volume have been used to discuss the type, the strength and the nature of intermolecular interactions betweenconstituent species. Comparison of the predicted values of static dielectric constant and refractive index of the liquid mixtures using various mixing rules with the experimentally determined values have been assessed in terms of Average Percentage Deviation (APD).

Forecast of Phase Diagram for the Synthesis of a Complex for the Detection of Cr6+ Ions.

A new organic complex (ANNBA) was synthesized using the solvent-free, solid-state reaction involving anthranilamide (AN)–m-nitrobenzoic acid (NBA). The established phase diagram specifies the formation of a complex in a 1:1 stoichiometric ratio which melts congruently at 142 °C. The diagram also infers the formation of two eutectics, E1 and E2, on either side of the complex with their respective melting at 118 and 106 °C. The stability and novelty of the synthesized complex was confirmed by differential scanning calorimetry, powder X-ray diffraction, and spectroscopic FTIR, 1H, and 13C NMR studies. The significant thermodynamic parameters such as the heat of mixing, the entropy of fusion, the roughness parameter, the interfacial energy, and excess thermodynamic functions have been studied. The novel complex (ANNBA) material displayed intense fluorescent emission as compared to the parent and the other well-known fluorescent organic material “pyrene.” The influence of solvent’s polarity on the absorption and emission of the complex has been studied in different solvents. Herein, we have displayed remarkable affinity of the complex toward hexavalent chromium ions in water, affecting its fluorescent property. We have deployed the synthesized complex as a turn-off fluorescent sensor to detect the most hazardous hexavalent chromium ions in water for the first time.

Excess iron supplementation induced hepatopancreas lipolysis, destroyed intestinal function in Pacific white shrimp Litopenaeus vannamei

So far, the adverse effects of excess Fe in shrimp have been ignored for years as it was thought that extra Fe supplementation was not needed in the practical diets. Nowadays, Fe concentration in commercial shrimp feed from feed enterprises could be around 301.34–545.5 mg/kg, which is mainly due to the fish meal containing up to 1500 mg/kg Fe. Therefore, the purpose of this experiment was to investigate the effects of Fe supplementation on the growth performance, tissue Fe deposition, hepatopancreas lipid metabolism, intestinal function in L. vannamei. The results showed that although growth performance was not influenced by the dietary Fe supplementation, excess Fe supplementation (955.00 mg/kg) significantly increased hepatopancreas Fe deposition and induced lipolysis. Moreover, excess Fe supplementation impaired intestinal immune function and disrupted microbiota homeostasis. These findings might provide partial theoretical evidence for the effect of dietary Fe supplementation on physiological metabolism in L. vannamei.

Derivation and consistency of the partial functions of a ternary system involving interaction coefficients

Abstract Margules equations are used to express the thermodynamics of a ternary system containing one solvent and two solutes in the vicinity of solvent, in terms of first order interaction coefficients of binary and ternary systems. Considering just the first order Margules coefficients, the resultant excess Gibbs energy function was convergent and the derived logarithmic activity coefficients of solvent and solutes were thermodynamically consistent. In the present study Margules equations are modified to get consistent equations. Partial functions of a ternary system are deduced using these modified equations via the excess Gibbs energy function. Derived partial functions are thermodynamically consistent and also deduced results are the same as those obtained using Maclaurin infinite series. Using the activity coefficient expressions of solvent and solutes, the activity coefficients of solvent and solute are calculated in Ni– Cr–Fe and Fe–Ti –C ternary systems, which are in excellent agreement with the experimental data.

Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures.

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions GE for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.

Maximal Generating Degrees of Powers of Homogeneous Ideals

The degree excess function 𝜖(I; n) is the difference between the maximal generating degree d(In) of the n-th power of a homogeneous ideal I of a polynomial ring and p(I)n, where p(I) is the leading coefficient of the asymptotically linear function d(In). It is shown that any non-increasing numerical function can be realized as a degree excess function, and there is a monomial ideal I whose 𝜖(I; n) has exactly a given number of local maxima. In the case of monomial ideals, an upper bound on 𝜖(I; n) is provided. As an application, it is shown that in the worst case, the so-called stability index of the Castelnuovo-Mumford regularity of a monomial ideal I must be at least an exponential function of the number of variables.

Activated Protein C Protects against Murine Contact Dermatitis by Suppressing Protease-Activated Receptor 2.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with excessive inflammation and defective skin barrier function. Activated protein C (APC) is a natural anticoagulant with anti-inflammatory and barrier protective functions. However, the effect of APC on AD and its engagement with protease activated receptor (PAR)1 and PAR2 are unknown. Methods: Contact hypersensitivity (CHS), a model for human AD, was induced in PAR1 knockout (KO), PAR2KO and matched wild type (WT) mice using 2,4-dinitrofluorobenzene (DNFB). Recombinant human APC was administered into these mice as preventative or therapeutic treatment. The effect of APC and PAR1KO or PARKO on CHS was assessed via measurement of ear thickness, skin histologic changes, inflammatory cytokine levels, Th cell phenotypes and keratinocyte function. Results: Compared to WT, PAR2KO but not PAR1KO mice displayed less severe CHS when assessed by ear thickness; PAR1KO CHS skin had less mast cells, lower levels of IFN-γ, IL-4, IL-17 and IL-22, and higher levels of IL-1β, IL-6 and TGF-β1, whereas PAR2KO CHS skin only contained lower levels of IL-22 and IgE. Both PAR1KO and PAR2KO spleen cells had less Th1/Th17/Th22/Treg cells. In normal skin, PAR1 was present at the stratum granulosum and spinosum, whereas PAR2 at the upper layers of the epidermis. In CHS, however, the expression of PAR1 and PAR2 were increased and spread to the whole epidermis. In vitro, compared to WT cells, PAR1KO keratinocytes grew much slower, had a lower survival rate and higher para permeability, while PAR2KO cells grew faster, were resistant to apoptosis and para permeability. APC inhibited CHS as a therapeutic but not as a preventative treatment only in WT and PAR1KO mice. APC therapy reduced skin inflammation, suppressed epidermal PAR2 expression, promoted keratinocyte growth, survival, and barrier function in both WT and PAR1KO cells, but not in PAR2KO cells. Conclusions: APC therapy can mitigate CHS. Although APC acts through both PAR1 and PAR2 to regulate Th and mast cells, suppression of clinical disease in mice is achieved mainly via inhibition of PAR2 alone. Thus, APC may confer broad therapeutic benefits as a disease-modifying treatment for AD.