Pleural Photodynamic Therapy and Surgery in Thoracic Cancer Patients with Pleural Spread

Pleural spread from non-small cell lung cancer is a difficult situation. The average survival in the situation is about 6–9 months. We investigate the current management of this challenging condition. Although, there is no much evidence found in the literature, we do see the pleural photodynamic therapy giving some promising light in the dark night. However, the patients still require complete neoadjuvant and adjuvant therapies, as well as radical tumor resection. Pleural PDT is one of the multi-modality treatments, which combined can achieve satisfactory oncological results. The long-term survival can be achieved in more than half the patients. However, the side effects of pleural PDT include skin hypersensitivity, trachea and esophageal perforation, and ARDS, which we should keep in mind

CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry.

Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus. HCV pseudoparticles infect liver-derived cells, supporting a model in which liver-specific molecules define HCV internalization. Three host cell molecules have been reported to be important entry factors or receptors for HCV internalization: scavenger receptor BI, the tetraspanin CD81, and the tight junction protein claudin-1 (CLDN1). None of the receptors are uniquely expressed within the liver, leading us to hypothesize that their organization within hepatocytes may explain receptor activity. Since CD81 and CLDN1 act as coreceptors during late stages in the entry process, we investigated their association in a variety of cell lines and human liver tissue. Imaging techniques that take advantage of fluorescence resonance energy transfer (FRET) to study protein-protein interactions have been developed. Aequorea coerulescens green fluorescent protein- and Discosoma sp. red-monomer fluorescent protein-tagged forms of CD81 and CLDN1 colocalized, and FRET occurred between the tagged coreceptors at comparable frequencies in permissive and nonpermissive cells, consistent with the formation of coreceptor complexes. FRET occurred between antibodies specific for CD81 and CLDN1 bound to human liver tissue, suggesting the presence of coreceptor complexes in liver tissue. HCV infection and treatment of Huh-7.5 cells with recombinant HCV E1-E2 glycoproteins and anti-CD81 monoclonal antibody modulated homotypic (CD81-CD81) and heterotypic (CD81-CLDN1) coreceptor protein association(s) at specific cellular locations, suggesting distinct roles in the viral entry process

Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells

<p>Abstract</p> <p>Background</p> <p>Previously we reported extensive gene expression reprogramming during epithelial to mesenchymal transition (EMT) of primary prostate cells. Here we investigated the hypothesis that specific histone and DNA methylations are involved in coordination of gene expression during EMT.</p> <p>Results</p> <p>Genome-wide profiling of histone methylations (H3K4me3 and H3K27me3) and DNA methylation (DNAMe) was applied to three cell lines at different stages of a stepwise prostate cell model involving EMT and subsequent accumulation of malignant features. Integrated analyses of epigenetic promoter modifications and gene expression changes revealed strong correlations between the dynamic changes of histone methylations and gene expression. DNA methylation was weaker associated with global gene repression, but strongly correlated to gene silencing when genes co-modified by H3K4me3 were excluded. For genes labeled with multiple epigenetic marks in their promoters, the level of transcription was associated with the net signal intensity of the activating mark H3K4me3 minus the repressive marks H3K27me3 or DNAMe, indicating that the effect on gene expression of bivalent marks (H3K4/K27me3 or H3K4me3/DNAMe) depends on relative modification intensities. Sets of genes, including epithelial cell junction and EMT associated fibroblast growth factor receptor genes, showed corresponding changes concerning epigenetic modifications and gene expression during EMT.</p> <p>Conclusions</p> <p>This work presents the first blueprint of epigenetic modifications in an epithelial cell line and the progeny that underwent EMT and shows that specific histone methylations are extensively involved in gene expression reprogramming during EMT and subsequent accumulation of malignant features. The observation that transcription activity of bivalently marked genes depends on the relative labeling intensity of individual marks provides a new view of quantitative regulation of epigenetic modification.</p

Superionic iron oxide-hydroxide in Earth’s deep mantle

H2O ice becomes a superionic phase under the high pressure and temperature conditions of deep planetary interiors of ice planets such as Neptune and Uranus, which affects interior structures and generates magnetic fields. The solid Earth, however, contains only hydrous minerals with negligible amount of ice. Here we combine high pressure and temperature electrical conductivity experiments, Raman spectroscopy, and first-principles simulations, to investigate the state of hydrogen in the pyrite type FeO2Hx (x ≤ 1) which is a potential H-bearing phase near the core-mantle boundary. We find that when the pressure increases beyond 73 GPa at room temperature, symmetric hydroxyl bonds are softened and the H+ (or proton) become diffusive within the vicinity of its crystallographic site. Increasing temperature under pressure, the diffusivity of hydrogen is extended beyond individual unit cell to cover the entire solid, and the electrical conductivity soars, indicating a transition to the superionic state which is characterized by freely-moving proton and solid FeO2 lattice. The highly diffusive hydrogen provides fresh transport mechanisms for charge and mass, which dictate the geophysical behaviors of electrical conductivity and magnetism, as well as geochemical processes of redox, hydrogen circulation, and hydrogen isotopic mixing in Earth’s deep mantle

Silicon carbide particulates incorporated into microalloyed steel surface using TIG: microstructure and properties

Surface metal matrix composites have been developed to enhance properties such as erosion, wear and corrosion of alloys. In this study, ~5 µm or ~75 µm SiC particulates were preplaced on a microalloyed steel. Single track surface zones were melted by a tungsten inert gas torch, and the effect of two heat inputs, 420Jmm-1 and 840 Jmm-1,compared. The results showed that the samples melted using 420Jmm-1 were crack-free. Pin-on-disk wear testing under dry sliding conditions were conducted. The effects of load and sliding velocity were used to characterise the performance of the crack-free samples. Microstructural and X-ray diffraction studies of the surface showed that the SiC had dissolved, and that martensite, was the main phase influencing the hardness

Thermal and thermomechanical behaviour of polycaprolactone and starch/polycaprolactone blends for biomedical applications

Polycaprolactone (PCL) and starch/PCL blends (SPCL) are shown to have the potential to be used in a range of biomedical applications and can be processed with conventional melting-based procedures. In this paper, the thermal and thermomechanical analyses of PCL and SPCL were performed, using DSC, optical microscopy and DMA. Starch effectively increased the non-isothermal crystallisation rate of PCL. Non-isothermal crystallisation kinetics was analyzed using Ozawa model, and a method, which combines the theories of Avrami and Ozawa. Starch effectively reinforced PCL and enhanced its damping properties, which indicated that SPCL could be more suitable than PCL in some biomedical applications, as it might help in the dissipation of the mechanical energy generated by the patient movements

Up-Regulation of Hepatitis C Virus Replication and Production by Inhibition of MEK/ERK Signaling

BACKGROUND: Viruses interact with and exploit the host cellular machinery for their multiplication and propagation. The MEK/ERK signaling pathway positively regulates replication of many RNA viruses. However, whether and how this signaling pathway affects hepatitis C virus (HCV) replication and production is not well understood. METHODS AND RESULTS: In this study, we took advantage of two well-characterized MEK/ERK inhibitors and MEK/ERK dominant negative mutants and investigated the roles of the MEK/ERK signaling pathway in HCV gene expression and replication. We showed that inhibition of MEK/ERK signaling enhanced HCV gene expression, plus- and minus-strand RNA synthesis, and virus production. In addition, we showed that this enhancement was independent of interferon-alpha (IFN-alpha) antiviral activity and did not require prior activation of the MEK/ERK signaling pathway. Furthermore, we showed that only MEK and ERK-2 but not ERK-1 was involved in HCV replication, likely through regulation of HCV RNA translation. CONCLUSIONS: Taken together, these results demonstrate a negative regulatory role of the MEK/ERK signaling pathway in HCV replication and suggest a potential risk in targeting this signaling pathway to treat and prevent neoplastic transformation of HCV-infected liver cells

Thermal Properties of Carbon Nanotube–Copper Composites for Thermal Management Applications

Carbon nanotube–copper (CNT/Cu) composites have been successfully synthesized by means of a novel particles-compositing process followed by spark plasma sintering (SPS) technique. The thermal conductivity of the composites was measured by a laser flash technique and theoretical analyzed using an effective medium approach. The experimental results showed that the thermal conductivity unusually decreased after the incorporation of CNTs. Theoretical analyses revealed that the interfacial thermal resistance between the CNTs and the Cu matrix plays a crucial role in determining the thermal conductivity of bulk composites, and only small interfacial thermal resistance can induce a significant degradation in thermal conductivity for CNT/Cu composites. The influence of sintering condition on the thermal conductivity depended on the combined effects of multiple factors, i.e. porosity, CNTs distribution and CNT kinks or twists. The composites sintered at 600°C for 5 min under 50 MPa showed the maximum thermal conductivity. CNT/Cu composites are considered to be a promising material for thermal management applications

Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis

<p>Abstract</p> <p>Background</p> <p>The objectives of this retrospective study was to evaluate the efficacy of stereotactic body radiation therapy (SBRT) for small non-resectable hepatocellular carcinoma (HCC) and SBRT combined with transarterial chemoembolization (TACE) for advanced HCC with portal vein tumor thrombosis (PVTT).</p> <p>Methods</p> <p>Thirty one patients with HCC who were treated with SBRT were used for the study. We studied 32 HCC lesions, where 23 lesions (22 patients) were treated targeting small non-resectable primary HCC, and 9 lesions (9 patients) targeting PVTT using the Cyberknife. All the 9 patients targeting PVTT received TACE for the advanced HCC. Tumor volume was 3.6–57.3 cc (median, 25.2 cc) and SBRT dose was 30–39 Gy (median, 36 Gy) in 3 fractions for consecutive days for 70–85% of the planned target volume.</p> <p>Results</p> <p>The median follow up was 10.5 months. The overall response rate was 71.9% [small HCC: 82.6% (19/23), advanced HCC with PVTT: 44.4% (4/9)], with the complete and partial response rates of 31.3% [small HCC: 26.1% (6/23), advanced HCC with PVTT: 11.1% (1/9)], and 50.0% [small HCC: 56.5% (13/23), advanced HCC with PVTT: 33.3% (3/9)], respectively. The median survival period of small HCC and advanced HCC with PVTT patients was 12 months and 8 months, respectively. No patient experienced Grade 4 toxicity.</p> <p>Conclusion</p> <p>SBRT for small HCC and SBRT combined with TACE for advanced HCC with PVTT showed feasible treatment modalities with minimal side effects in selected patients with primary HCC.</p

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively