Irradiation resistance, microstructure and mechanical properties of nanostructured (TiZrHfVNbTa)N coatings

Nitrides of high-entropy alloys (TiHfZrNbVTa)N were fabricated using cathodic-vacuum-arc-vapor deposition method. Morphology and topology of the surface of the coatings, roughness, elemental and phase composition, microstructure and mechanical properties were investigated. Dependence of deposition parameters on surface morphology and elemental composition was demonstrated. Influence of the heavy negative charged Au ions implantation on phase structure, microstructure and hardness of nitride (TiHfZrNbVTa)N coatings was investigated

Structural features and physico-mechanical properties of AlN-TiB2-TiSi2 amorphous-like coatings

The coating of the AlN–TiB2–TiSi2 system has been produced by the magnetron sputtering of a target. At the hightemperature (900 and 1300°C) actions the coating crystallization to form crystallites of sizes 11–25 nm has been observed. It has been defined that the amorphouslike structure is promising for the use of these coatings as diffusion barriers both as the independent elements and a contacting layer in multilayer wearresistant coatings. It has been shown that the use of the resultant composite as an effec tive protective coating for cutting tools will make it possible to increase the tools wear resistance by more than 30% at the temperature up to 1300°C in the cutting zone

Structural features and physico-mechanical properties of AlN-TiB2-TiSi2 amorphous-like coatings

The coating of the AlN–TiB2–TiSi2 system has been produced by the magnetron sputtering of a target. At the hightemperature (900 and 1300°C) actions the coating crystallization to form crystallites of sizes 11–25 nm has been observed. It has been defined that the amorphouslike structure is promising for the use of these coatings as diffusion barriers both as the independent elements and a contacting layer in multilayer wearresistant coatings. It has been shown that the use of the resultant composite as an effec tive protective coating for cutting tools will make it possible to increase the tools wear resistance by more than 30% at the temperature up to 1300°C in the cutting zone

Influence of residual pressure and ion implantation on the structure, elemental composition, and properties of (TiZrAlYNb)N nitrides

The nitrides of highentropy alloys, (TiZrAlYNb)N, fabricated by cathodic vacuum arc evaporation are studied with electron microscopy, atomic force microscopy, laser scanning microscopy; energydispersive Xray analysis, Xray phase analysis, timeofflight secondaryion mass spectrometry; and hardness measurements. It is found that the deposition parameters influence the structure, surface morphology, element distribution, and mechanical properties. The structural–phase state of the coatings before and after the ion implantation of heavy negative gold ions Au– are compared. DOI: 10

Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells

Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are among the most frequent inflammatory skin diseases and are both determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp3−/− and Pglyrp4−/− mice (but not Pglyrp2−/− mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp3−/− and Pglyrp4−/− mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp3−/− and Pglyrp4−/− mice, which results in more severe inflammation and keratinocyte proliferation. This mechanism is supported by decreased inflammation in Pglyrp3−/− mice following in vivo induction of Treg cells by vitamin D or after neutralization of IL-17. By contrast, Pglyrp1−/− mice develop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation, which protects the skin from exaggerated inflammatory response to cell activators and allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin

TLR2, but Not TLR4, Is Required for Effective Host Defence against Chlamydia Respiratory Tract Infection in Early Life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases

Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model

Influence of residual pressure and ion implantation on the structure, elemental composition, and properties of (TiZrAlYNb)N nitrides

The nitrides of highentropy alloys, (TiZrAlYNb)N, fabricated by cathodic vacuum arc evaporation are studied with electron microscopy, atomic force microscopy, laser scanning microscopy; energydispersive Xray analysis, Xray phase analysis, timeofflight secondaryion mass spectrometry; and hardness measurements. It is found that the deposition parameters influence the structure, surface morphology, element distribution, and mechanical properties. The structural–phase state of the coatings before and after the ion implantation of heavy negative gold ions Au– are compared. DOI: 10

Praziquantel Facilitates IFN-γ-Producing CD8+ T Cells (Tc1) and IL-17-Producing CD8+ T Cells (Tc17) Responses to DNA Vaccination in Mice

BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8(+) T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH) in C57BL/6 mice. Furthermore, the induced CD8(+) T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-γ knockout (KO) mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8(+) T cells from wild type mice, but not the counterpart from IFN-γ KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8(+) T cell-based immunotherapy that breaks tolerance to HBsAg