Tinagl1 Gene Therapy Suppresses Growth and Remodels the Microenvironment of Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat and is responsible for approximately 12% of breast cancer cases in the US per year. In 2019, the protein Tinagl1 was identified as a key factor for improved prognoses in certain TNBC patients. While the intracellular mechanism of action has been thoroughly studied, little is known about the role of Tinagl1 in the tumor microenvironment. In this study, we developed a lipid nanoparticle-based gene therapy to directly target the expression of Tinagl1 in tumor cells for localized expression. Additionally, we sought to characterize the changes to the tumor microenvironment induced by Tinagl1 treatment, with the goal of informing future choices for combination therapies including Tinagl1. We found that Tinagl1 gene therapy was able to slow tumor growth from the first dose and that the effects held steady for nearly a week following the final dose. No toxicity was found with this treatment. Additionally, the use of Tinagl1 increases the tumor vasculature by 3-fold but does not increase the tumor permeability or risk of metastasis. However, the increase in vasculature arising from Tinagl1 therapy reduced the expression of Hif1a significantly (p < 0.01), which may decrease the risk of drug resistance

Effect of Long-Term Storage on Microstructure and Microhardness Stability in OFHC Copper Processed by High-Pressure Torsion

Tests are conducted to evaluate the effect of long-term storage on the microstructure and microhardness of an oxygen-free high conductivity (OFHC) copper after processing by high-pressure torsion (HPT) for various numbers of revolutions at ambient temperature. Results are presented for samples subjected to storage at room temperature through periods of either 1.25 or 7 years. The results show that an increase in storage time leads to a coarsening of the ultrafine-grained structure produced by HPT processing and a corresponding decrease in the microhardess where this is associated with the occurrence of recrystallization and grain growth. Plots of hardness against equivalent strain reveal a three-stage behavior with much lower hardness values over a range of equivalent strains of ~2-8. This behavior is similar after both storage periods but the hardness values are lower and the grain sizes are larger after storage for the longer time. The results demonstrate that long-term storage has a significantly detrimental effect on the microstructure and hardness of ultrafine-grained OFHC Cu

The generalized parton distributions of the nucleon in the NJL model based on the Faddeev approach

We study the generalized parton distributions, including the helicity-flip ones, using Nambu-Jona-Lasinio model based on a relativistic Faddeev approach with `static approximation'. Sum rules relating the generalized parton distributions to nucleon electromagnetic form factors are satisfied. Moreover, quark-antiquark contributions in the region $-\xi<x<\xi$ are non-vanishing. Our results are qualitatively similar to those calculated with Radyushkin's double distribution ansatz using forward parton distribution functions calculated in the NJL model as inputs.Comment: 35 pages, 15 figure

Macrosegregation During Dendritic Arrayed Growth of Hypoeutectic Pb-Sn Alloys: Influence of Primary Arm Spacing and Mushy Zone Length

Thermosolutal convection in the dendritic mushy zone occurs during directional solidification of hypoeutectic lead tin alloys in a positive thermal gradient, with the melt on the top and the solid below. This results in macrosegregation along the length of the solidified samples. The extent of macrosegregation increases with increasing primary dendrite spacings for constant mushy zone length. For constant primary spacings, the macrosegregation increases with decreasing mushy zone length. Presence of convection reduces the primary dendrite spacings. However, convection in the interdendritic melt has significantly more influence on the spacings as compared with that in the overlying melt, which is caused by the solutal buildup at the dendrite tips

Macrosegregation Caused by Thermosolutal Convection During Directional Solidification of Pb-Sb Alloys

Pb-2.2 and 5.8 wt pet Sb alloys were directionally solidified with a positive thermal gradient of 140 K cm(-1) at growth speeds ranging from 0.8 to 30 mu m s(-1), and then quenched to retain the mushy-zone morphology. Chemical analysis along the length of the directionally solidified portion and in the quenched melt ahead of the dendritic array showed extensive longitudinal macrosegregation, Cellular morphologies growing at smaller growth speeds are associated with larger amounts of macrosegregation as compared with the dendrites growing at higher growth speeds. Convection is caused, mainly, by the density inversion in the overlying melt ahead of the cellular/dendritic array because of the antimony enrichment at the array tip. Mixing of the interdendritic and bulk melt during directional solidification is responsible for the observed longitudinal macrosegregation

Evolution of Non-Equilibrium Profile in Adsorbate Layer under Compressive Strain

We investigate the time evolution of an initial step profile separating a bare substrate region from the rest of the compressively strained adsorbate layer near a commensurate to incommensurate transition. The rate of profile evolution as a function of the mismatch, coverage and the strength of the substrate potential are determined by Brownian molecular dynamics simulations. We find that the results are qualitatively similar to those observed for the Pb/Si(111) system. The anomalously fast time evolution and sharpness of the non-equilibrium profile can be understood through the domain wall creation at the boundary and its subsequent diffusion into the interior of the adsorbate layer.Comment: 6 pages, 7 figures, Tribology Letter

Comparisons of self-annealing behaviour of HPT-processed high purity Cu and a Pb–Sn alloy.

Early published results have demonstrated that high purity Cu and a Pb–62% Sn alloy exhibit very different behaviour during high-pressure torsion (HPT) processing at room temperature and subsequent room temperature storage. High purity Cu showed strain hardening behaviour with a refined grain structure during HPT processing whereas a Pb–62% Sn alloy displayed a strain weakening behaviour because the hardness values after HPT processing were significantly lower than in the initial as-cast condition even though the grain size was reduced. During room temperature storage after HPT processing, high purity Cu with lower numbers of rotations softened with the time of storage due to local recrystallization and abnormal grain growth whereas the Pb–62% Sn alloy hardened with the time of storage accompanied by grain growth. Through comparisons and analysis, it is shown that the low absolute melting point and the high homologous temperature at room temperature in the Pb–62% Sn alloy contribute to the increase in hardness with coarsening grain size during room temperature storage

Novel patterning of nano-bioceramics: template-assisted electrohydrodynamic atomization spraying

The ability to create patterns of bioactive nanomaterials particularly on metallic and other types of implant surfaces is a crucial feature in influencing cell response, adhesion and growth. In this report, we uncover and elucidate a novel method that allows the easy deposition of a wide variety of predetermined topographical geometries of nanoparticles of a bioactive material on both metallic and non-metallic surfaces. Using different mesh sizes and geometries of a gold template, hydroxyapatite nanoparticles suspended in ethanol have been electrohydrodynamically sprayed on titanium and glass substrates under carefully designed electric field conditions. Thus, different topographies, e.g. hexagonal, line and square, from hydroxyapatite nanoparticles were created on these substrates. The thickness of the topography can be controlled by varying the spraying time

The muon anomalous magnetic moment and a new light gauge boson

It is shown that the 2.6 $\sigma$ discrepancy between the predicted and recently measured value of the anomalous magnetic moment of positive muons could be explained by the existence of a new light gauge boson X with a mass $M_X \leq O(5) GeV$. Phenomenological bounds on the X coupling are discussed.Comment: 7 pages, version to appear in PL

Hot air drying combined vacuum-filling nitrogen drying of apple slices: Drying characteristics and nutrients

[EN] In this paper, hot air drying (HAD) was applied when moisture content of apple slices range from 50% to 86%, and then vacuum-filling nitrogen drying (VFND) was used till moisture content reaching 7%. Results showed that, the drying rate of apple slice during VFND period increased with temperature increment and decreased with increment of slice thickness; compared to freezing dried samples, samples dried in this research were owned lower Vc and higher flavonoid; when HAD (70℃,3.0m/s)+VFND(relative pressure 0.08MPa, 50℃) and thickness of 6.0mm, nutrients reached better levels: retentions of Vc, total phenolics and flavonoid were 1.63mg/100g, 4.07mg/100g and 2.10mg/100g, respectively.The work was financially supported by the Fundamental Research Funds for the Central Universities of China (NO. GK201503072 and GK201601007).Huang, X.; Li, T.; Li, S.; Wu, Z.; Xue, J. (2018). Hot air drying combined vacuum-filling nitrogen drying of apple slices: Drying characteristics and nutrients. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 811-818. https://doi.org/10.4995/IDS2018.2018.7477OCS81181