Hierarchy of topological transitions in a network liquid.

The representation of complex systems as networks has become a critical tool across many fields of science. In the context of physical networks, such as biological neural networks, vascular networks, or network liquids where the nodes and edges occupy volume in three-dimensional space, the question of how they become densely packed is of special importance. Here, we investigate a model network liquid, which is known to densify via two successive liquid-liquid phase transitions (LLPTs). We elucidate the importance of rings-cyclic paths formed by bonded particles in the networks-and their spatial disposition in understanding the structural changes that underpin the increase in density across the LLPTs. Our analyses demonstrate that the densification of these networks is primarily driven by the formation of linked rings, and the LLPTs correspond to a hierarchy of topological transitions where rings form the fundamental building blocks. We envisage entanglement to emerge as a general mechanism for densification, with wide implications for the embedding of physical networks, especially in confined spaces.

Adaptive immune receptor features related to breast cancer tissue in Kenyan patients: high immunoglobulin gene expression and high levels of gamma-delta T-cells.

BACKGROUND: Characterization of the breast cancer (BC) immune response may provide information for a point of intervention, such as application of immunotherapeutic treatments. In this study, we sought to recover and characterize the adaptive immune receptor (IR) recombination reads from genomics files representing Kenyan patients, to better understand the immune response specifically related to those patients. METHODS: We used a previously applied algorithm and software to obtain productive IR recombination reads from cancer and adjacent normal tissue samples representing 22 Kenyan BC patients. RESULTS: From both the RNAseq and exome files, there were significantly more T-cell receptor (TCR) recombination reads recovered from tumor samples compared to marginal tissue samples. Also, the immunoglobulin (IG) genes were expressed at a much higher level than the TCR genes (p-value = 0.0183) in the tumor samples. And, the tumor IG CDR3s consistently represented more positively charged amino acid R-groups, in comparison to the marginal tissue, IG CDR3s. CONCLUSION: For Kenyan patients, a high level of IG expression, representing specific CDR3 chemistries, was associated with BC. These results lay the foundation for studies that could support specific immunotherapeutic interventions for Kenyan BC patients.

Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy.

Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (<40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of <0.5- or >2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD.

Biotechnological development of Trichoderma-based formulations for biological control.

Trichoderma spp. are a genus of well-known fungi that promote healthy growth and modulate different functions in plants, as well as protect against various plant pathogens. The application of Trichoderma and its propagules as a biological control method can therefore help to reduce the use of chemical pesticides and fertilizers in agriculture. This review critically discusses and analyzes groundbreaking innovations over the past few decades of biotechnological approaches to prepare active formulations containing Trichoderma. The use of various carrier substances is covered, emphasizing their effects on enhancing the shelf life, viability, and efficacy of the final product formulation. Furthermore, the use of processing techniques such as freeze drying, fluidized bed drying, and spray drying are highlighted, enabling the development of stable, light-weight formulations. Finally, promising microencapsulation techniques for maximizing the performance of Trichoderma spp. during application processes are discussed, leading to the next-generation of multi-functional biological control formulations. KEY POINTS: • The development of carrier substances to encapsulate Trichoderma propagules is highlighted. • Advances in biotechnological processes to prepare Trichoderma-containing formulations are critically discussed. • Current challenges and future outlook of Trichoderma-based formulations in the context of biological control are presented.

Biopolymer-based emulsions for the stabilization of Trichoderma atrobrunneum conidia for biological control.

Trichoderma spp. are ubiquitous soil-borne fungi that are widely used in biological control to promote and regulate healthy plant growth, as well as protect against plant pathogens. However, as with many biological materials, the relative instability of Trichoderma propagules limits its practical use in industrial applications. Therefore, there has been significant research interest in developing novel formulations with various carrier substances that are compatible with these fungal propagules and can enhance the shelf-life and overall efficacy of the Trichoderma. To this end, herein, we investigate the use of a variety of biopolymers and nanoparticles for the stabilization of Trichoderma atrobrunneum T720 conidia for biological control. The best-performing agents-agar and cellulose nanocrystals (CNC)-were then used in the preparation of oil-in-water emulsions to encapsulate conidia of T720. Emulsion properties including oil type, oil:water ratio, and biopolymer/particle concentration were investigated with respect to emulsion stability, droplet size, and viability of T720 conidia over time. Overall, agar-based formulations yielded highly stable emulsions with small droplet sizes, showing no evidence of drastic creaming, or phase separation after 1 month of storage. Moreover, agar-based formulations were able to maintain ~ 100% conidial viability of T720 after 3 months of storage, and over 70% viability after 6 months. We anticipate that the results demonstrated herein will lead to a new generation of significantly improved formulations for practical biological control applications. KEY POINTS: • Various biopolymers were evaluated for improving the stability of Trichoderma conidia • Oil in water emulsions was prepared using cellulose nanocrystals and agar as interface stabilizers • Agar-based emulsions showed ~ 100% viability for encapsulated conidia after 3 months of storage.

Amazon deforestation: simulated impact of Brazil's proposed BR-319 highway project.

The scenario of deforestation in the Amazon may change with the reconstruction of Highway BR-319, a long-distance road that will expand the region's agricultural frontier towards the north and west of the Western Amazon, stretches that until then have extensive areas of primary forest due to the hard access. We simulate the deforestation that would be caused by the reconstruction and paving of Highway BR-319 in Brazil's state of Amazonas for the period from 2021 to 2100. The scenarios were based on the historical dynamics of deforestation in the state of Amazonas (business as usual, or BAU). Two deforestation scenarios were developed: (a) BAU_1, where Highway BR-319 is not reconstructed, maintaining its current status, and (b) BAU_2, where the reconstruction and paving of the highway will take place in 2025, favoring the advance of the deforestation frontier to the northern and western portion of the state of Amazonas. In the scenario where the highway reconstruction is foreseen (BAU_2), the results show that deforestation increased by 60% by 2100 compared to the scenario without reconstruction (BAU_1), demonstrating that paving would increase deforestation beyond the limits of the highway's official buffer area (40 km). The study showed that protected areas (conservation units and indigenous lands) help to maintain forest cover in the Amazon region. At the same time, it shows how studies like this one can help in decision-making.

Results of the United States Food and Drug Administration Clinical Trial of the CustomFlex Artificial Iris.

PURPOSE: To evaluate safety and efficacy of a custom-manufactured artificial iris device (CustomFlex Artificial Iris; HumanOptics AG) for the treatment of congenital and acquired iris defects. DESIGN: Multicenter, prospective, unmasked, nonrandomized, interventional clinical trial. PARTICIPANTS: Patients with photophobia, sensitivity secondary to partial or complete congenital or acquired iris defects, or both. METHODS: Eyes were implanted from November 26, 2013, to December 1, 2017, with a custom, foldable artificial iris by 1 of 4 different surgical techniques. Patients were evaluated 1 day, 1 week, and 1, 3, 6, and 12 months after surgery. At each examination, slit-lamp findings, intraocular pressure, implant position, subjective visual symptoms, and complications were recorded. Corrected distance visual acuity (CDVA) and endothelial cell density (ECD) were measured at 3, 6, or 12 months as additional safety evaluations. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to assess health-related quality of life affected by vision. The Global Aesthetic Improvement Scale was used to assess cosmetic results. MAIN OUTCOME MEASURES: Photosensitivity, glare, visual symptoms, NEI VFQ-25 score, Global Aesthetic Improvement Scale rating, prosthesis-related adverse events, intraocular lens (IOL)-related adverse events, and surgery-related adverse events 12 months after surgery. RESULTS: At the 12-month postoperative examination, a 59.7% reduction in marked to severe daytime light sensitivity (P < 0.0001), a 41.5% reduction in marked to severe nighttime light sensitivity (P < 0.0001), a 53.1% reduction in marked to severe daytime glare (P < 0.0001), and a 48.5% reduction in severe nighttime glare (P < 0.0001) were found. A 15.4-point improvement (P < 0.0001) in the NEI VFQ-25 total score was found, and 93.8% of patients reported an improvement in cosmesis as measured by the Global Aesthetic Improvement Scale 12 months after surgery. No loss of CDVA of > 2 lines related to the device was found. Median ECD loss was 5.3% at 6 months after surgery and 7.2% at 12 months after surgery. CONCLUSIONS: The artificial iris surpassed all key safety end points for adverse events related to the device, IOL, or implant surgery and met all key efficacy end points, including decreased light and glare sensitivity, improved health-related quality of life, and satisfaction with cosmesis. The device is safe and effective for the treatment of symptoms and an unacceptable cosmetic appearance created by congenital or acquired iris defects.

Endothelial TNF receptor 2 induces IRF1 transcription factor-dependent interferon-ß autocrine signaling to promote monocyte recruitment.

Endothelial-dependent mechanisms of mononuclear cell influx are not well understood. We showed that acute stimulation of murine microvascular endothelial cells expressing the tumor necrosis factor receptors TNFR1 and TNFR2 with the soluble cytokine TNF led to CXCR3 chemokine generation. The TNF receptors signaled through interferon regulatory factor-1 (IRF1) to induce interferon-ß (IFN-ß) and subsequent autocrine signaling via the type I IFN receptor and the transcription factor STAT1. Both TNFR2 and TNFR1 were required for IRF1-IFNß signaling and, in human endothelial cells TNFR2 expression alone induced IFN-ß signaling and monocyte recruitment. In vivo, TNFR1 was required for acute renal neutrophil and monocyte influx after systemic TNF treatment, whereas the TNFR2-IRF1-IFN-ß autocrine loop was essential only for macrophage accumulation. In a chronic model of proliferative nephritis, IRF1 and renal-expressed TNFR2 were essential for sustained macrophage accumulation. Thus, our data identify a pathway in endothelial cells that selectively recruits monocytes during a TNF-induced inflammatory response.

Isolation and molecular characterization of a tomato brown rugose fruit virus mutant breaking the tobamovirus resistance found in wild Solanum species.

A new tobamovirus named tomato brown rugose fruit virus (ToBRFV) overcomes the effect of the Tm-1, Tm-2, and Tm-22 resistance genes introgressed from wild Solanum species into cultivated tomato (Solanum lycopersicum). Here, we report the isolation and molecular characterization of a spontaneous mutant of ToBRFV that breaks resistance in an unknown genetic background, demonstrated recently in Solanum habrochaites and Solanum peruvianum. The wild isolate ToBRFV-Tom2-Jo and the mutant ToBRFV-Tom2M-Jo were fully sequenced and compared to each other and to other ToBRFV sequences available in the NCBI GenBank database. Sequence analysis revealed five nucleotide substitutions in the ToBRFV-Tom2M-Jo genome compared to ToBRFV-Tom2-Jo. Two substitutions were located in the movement protein (MP) gene and resulted in amino acid changes in the 30-kDa MP (Phe22 → Asn and Tyr82 → Lys). These substitutions were not present in any of the previously described ToBRFV isolates. No amino acid changes were found in the 126-kDa and 183-kDa replicase proteins or the 17.5-kDa coat protein. Our data strongly suggest that breaking the newly discovered resistance in wild tomatoes is associated with one or two mutations on the MP gene of ToBRFV.

Reactive Molecular Dynamics Simulations of the Depolymerization of Polyethylene Using Graphene-Oxide-Supported Platinum Nanoparticles.

While plastic materials offer many benefits to society, the slow degradation and difficulty in recycling plastics raise important environmental and sustainability concerns. Traditional recycling efforts often lead to materials with inferior properties and correspondingly lower value, making them uneconomical to recycle. Recent efforts have shown promising chemical pathways for converting plastic materials into a wide range of value-added products, feedstocks or monomers. This is commonly referred to as "chemical recycling". Here, we use reactive molecular dynamics (MD) simulations to study the catalytic process of depolymerization of polyethylene (PE) using platinum (Pt) nanoparticles (NPs) in comparison to PE pyrolysis (thermal degradation). We apply a simple kinetic model to our MD results for the catalytic reaction rate as a function of temperature, from which we obtain the activation energy of the reaction, which shows the that the Pt NPs reduce the barrier for depolymerization. We further evaluate the molecular mass distribution of the reaction products to gain insight into the influence of the Pt NPs on reaction selectivity. Our results demonstrate the potential for the reactive MD method to help the design of recycling approaches for polymer materials.

NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis.

Proinflammatory stimuli elicit rapid transcriptional responses via transduced signals to master regulatory transcription factors. To explore the role of chromatin-dependent signal transduction in the atherogenic inflammatory response, we characterized the dynamics, structure, and function of regulatory elements in the activated endothelial cell epigenome. Stimulation with tumor necrosis factor alpha prompted a dramatic and rapid global redistribution of chromatin activators to massive de novo clustered enhancer domains. Inflammatory super enhancers formed by nuclear factor-kappa B accumulate at the expense of immediately decommissioned, basal endothelial super enhancers, despite persistent histone hyperacetylation. Mass action of enhancer factor redistribution causes momentous swings in transcriptional initiation and elongation. A chemical genetic approach reveals a requirement for BET bromodomains in communicating enhancer remodeling to RNA Polymerase II and orchestrating the transition to the inflammatory cell state, demonstrated in activated endothelium and macrophages. BET bromodomain inhibition abrogates super enhancer-mediated inflammatory transcription, atherogenic endothelial responses, and atherosclerosis in vivo.

Relating dynamic free volume to cooperative relaxation in a glass-forming polymer composite.

There are a variety of complementary descriptions of the temperature dependence of the structural relaxation time τ in glass-forming materials, which we interpret positively as suggesting an underlying unified description. We examine the inter-relation between the string model, an outgrowth of the Adam and Gibbs approach that emphasizes collective particle exchange motion, and the localization model, which emphasizes the volume explored by particles in their caged states, a kind of dynamic "free volume." Each model of liquid dynamics is described by a limited set of parameters that must be interrelated if both descriptions simultaneously describe the relaxation behavior. We pursue the consequences of this idea by performing coarse-grained molecular simulations of polymer melts with additives of variable size and interaction strength with the polymer matrix, thereby significantly altering the relaxation of the composite material. Both the string and localization models describe our relaxation time data well, and a comparison of the model parameters allows us to relate the local caging scale ⟨u2⟩ (the Debye-Waller parameter) to the entropy of activation for molecular rearrangements in the string model, thereby developing a bridge between these seemingly disparate approaches to liquid dynamics.

The effect of nanoparticle softness on the interfacial dynamics of a model polymer nanocomposite.

The introduction of soft organic nanoparticles (NPs) into polymer melts has recently expanded the material design space for polymer nanocomposites, compared to traditional nanocomposites that utilize rigid NPs, such as silica, metallic NPs, and other inorganic NPs. Despite advances in the fabrication and characterization of this new class of materials, the effect of NP stiffness on the polymer structure and dynamics has not been systematically investigated. Here, we use molecular dynamics to investigate the segmental dynamics of the polymer interfacial region of isolated NPs of variable stiffness in a polymer matrix. When the NP-polymer interactions are stronger than the polymer-polymer interactions, we find that the slowing of segmental dynamics in the interfacial region is more pronounced for stiff NPs. In contrast, when the NP-polymer interaction strength is smaller than the matrix interaction, the NP stiffness has relatively little impact on the changes in the polymer interfacial dynamics. We also find that the segmental relaxation time τα of segments in the NP interfacial region changes from values lower than to higher than the bulk material when the NP-polymer interaction strength is increased beyond a "critical" strength, reminiscent of a binding-unbinding transition. Both the NP stiffness and the polymer-surface interaction strength can thus greatly influence the relative segmental relaxation and interfacial mobility in comparison to the bulk material.

Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.

BACKGROUND: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. METHODS: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. RESULTS: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. CONCLUSIONS: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways.

Humoral immunity is reliant on efficient recruitment of circulating naïve B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization in human tonsils and LNs and unearthed conspicuously high expression of Gal-9 on high endothelial and post-capillary venules. Adhesion analyses showed that Gal-9 can bridge human circulating and naïve B cells to vascular endothelial cells (EC), while decelerating transendothelial migration. Moreover, Gal-9 interactions with naïve B cells induced global transcription of gene families related to regulation of cell signaling and membrane/cytoskeletal dynamics. Signaling lymphocytic activation molecule F7 (SLAMF7) was among key immunoregulators elevated by Gal-9-binding, while SLAMF7's cytosolic adapter EAT-2, which is required for cell activation, was eliminated. Gal-9 also activated phosphorylation of pro-survival factor, ERK. Together, these data suggest that Gal-9 promotes B cell - EC interactions while delivering anergic signals to control B cell reactivity.

Targeted inhibition of CD47-SIRPα requires Fc-FcγR interactions to maximize activity in T-cell lymphomas.

Antibodies that bind CD47 on tumor cells and prevent interaction with SIRPα on phagocytes are active against multiple cancer types including T-cell lymphoma (TCL). Here we demonstrate that surface CD47 is heterogeneously expressed across primary TCLs, whereas major histocompatibility complex (MHC) class I, which can also suppress phagocytosis, is ubiquitous. Multiple monoclonal antibodies (mAbs) that block CD47-SIRPα interaction promoted phagocytosis of TCL cells, which was enhanced by cotreatment with antibodies targeting MHC class I. Expression levels of surface CD47 and genes that modulate CD47 pyroglutamation did not correlate with the extent of phagocytosis induced by CD47 blockade in TCL lines. In vivo treatment of multiple human TCL patient-derived xenografts or an immunocompetent murine TCL model with a short course of anti-CD47 mAb markedly reduced lymphoma burden and extended survival. Depletion of macrophages reduced efficacy in vivo, whereas depletion of neutrophils had no effect. F(ab')2-only fragments of anti-CD47 antibodies failed to induce phagocytosis by human macrophages, indicating a requirement for Fc-Fcγ receptor interactions. In contrast, F(ab')2-only fragments increased phagocytosis by murine macrophages independent of SLAMF7-Mac-1 interaction. Full-length anti-CD47 mAbs also induced phagocytosis by Fcγ receptor-deficient murine macrophages. An immunoglobulin G1 anti-CD47 mAb induced phagocytosis and natural killer cell-mediated cytotoxicity of TCL cells that was augmented by cotreatment with mogamulizumab, an anti-CCR4 mAb, or a mAb blocking MHC class I. These studies help explain the disparate activity of monotherapy with agents that block CD47 in murine models compared with patients. They also have direct translational implications for the deployment of anti-CD47 mAbs alone or in combination.

Explaining the Sensitivity of Polymer Segmental Relaxation to Additive Size Based on the Localization Model.

We use molecular simulations to examine how the dynamics of a coarse-grained polymer melt are altered by additives of variable size and interaction strength with the polymer matrix. The effect of diluent size σ on polymer dynamics changes significantly when its size is comparable to the polymer segment size. For each σ, we show that the localization model (LM) quantitatively describes the dependence of the segmental relaxation time τ on temperature T in terms of dynamic free volume, quantified by the Debye-Waller factor ⟨u^{2}⟩. Within this model, we show that the additive size alone controls the functional form of the T dependence. The LM parameters reach asymptotic values when the diluent size exceeds the monomer size, converging to a limit applicable to macroscopic interfaces.

Melanized-Cationic Cellulose Nanofiber Foams for Bioinspired Removal of Cationic Dyes.

In recent years, water pollution has developed into a severe environmental and public health problem due to rapid urbanization and industrialization, especially in some developing countries. Finding solutions to tackle water pollution is urgently required and is of global importance. Currently, a range of water treatment methods are available; however, a water remediation process that is simple, inexpensive, eco-friendly, and effective for the removal of pollutants down to ppm/ppb concentrations has long been sought after. Herein, we describe a novel approach using fungal melanin for developing melanized-cationic cellulose nanofiber (melanized-C-CNF) foams that can successfully remove pollutants in water systems. The foam can be recycled several times while retaining its adsorption/desorption property, indicating high practicability for adsorbing the cationic dye crystal violet. This work highlights the opportunity to combine both the advanced features of sustainable polymers such as cellulose and the unique properties of fungal melanin to manufacture biohybrid composites for water purification.

Activation free energy gradient controls interfacial mobility gradient in thin polymer films.

We examine the mobility gradient in the interfacial region of substrate-supported polymer films using molecular dynamics simulations and interpret these gradients within the string model of glass-formation. No large gradients in the extent of collective motion exist in these simulated films, and an analysis of the mobility gradient on a layer-by-layer basis indicates that the string model provides a quantitative description of the relaxation time gradient. Consequently, the string model indicates that the interfacial mobility gradient derives mainly from a gradient in the high-temperature activation enthalpy ΔH0 and entropy ΔS0 as a function of depth z, an effect that exists even in the high-temperature Arrhenius relaxation regime far above the glass transition temperature. To gain insight into the interfacial mobility gradient, we examined various material properties suggested previously to influence ΔH0 in condensed materials, including density, potential and cohesive energy density, and a local measure of stiffness or u2(z)-3/2, where u2(z) is the average mean squared particle displacement at a caging time (on the order of a ps). We find that changes in local stiffness best correlate with changes in ΔH0(z) and that ΔS0(z) also contributes significantly to the interfacial mobility gradient, so it must not be neglected.