Scattering of Noncommutative Waves and Solitons in a Supersymmetric Chiral Model in 2+1 Dimensions

Interactions of noncommutative waves and solitons in 2+1 dimensions can be analyzed exactly for a supersymmetric and integrable U(n) chiral model extending the Ward model. Using the Moyal-deformed dressing method in an antichiral superspace, we construct explicit time-dependent solutions of its noncommutative field equations by iteratively solving linear equations. The approach is illustrated by presenting scattering configurations for two noncommutative U(2) plane waves and for two noncommutative U(2) solitons as well as by producing a noncommutative U(1) two-soliton bound state.Comment: 1+13 pages; v2: reference added, version published in JHE

Yang-Mills instantons and dyons on homogeneous G_2-manifolds

We consider Lie G-valued Yang-Mills fields on the space R x G/H, where G/H is a compact nearly K"ahler six-dimensional homogeneous space, and the manifold R x G/H carries a G_2-structure. After imposing a general G-invariance condition, Yang-Mills theory with torsion on R x G/H is reduced to Newtonian mechanics of a particle moving in R^6, R^4 or R^2 under the influence of an inverted double-well-type potential for the cases G/H = SU(3)/U(1)xU(1), Sp(2)/Sp(1)xU(1) or G_2/SU(3), respectively. We analyze all critical points and present analytical and numerical kink- and bounce-type solutions, which yield G-invariant instanton configurations on those cosets. Periodic solutions on S^1 x G/H and dyons on iR x G/H are also given.Comment: 1+26 pages, 14 figures, 6 miniplot

Small Molecules Targeted to a Non-Catalytic “RVxF” Binding Site of Protein Phosphatase-1 Inhibit HIV-1

HIV-1 Tat protein recruits host cell factors including CDK9/cyclin T1 to HIV-1 TAR RNA and thereby induces HIV-1 transcription. An interaction with host Ser/Thr protein phosphatase-1 (PP1) is critical for this function of Tat. PP1 binds to a Tat sequence, Q35VCF38, which resembles the PP1-binding “RVxF” motif present on PP1-binding regulatory subunits. We showed that expression of PP1 binding peptide, a central domain of Nuclear Inhibitor of PP1, disrupted the interaction of HIV-1 Tat with PP1 and inhibited HIV-1 transcription and replication. Here, we report small molecule compounds that target the “RVxF”-binding cavity of PP1 to disrupt the interaction of PP1 with Tat and inhibit HIV-1 replication. Using the crystal structure of PP1, we virtually screened 300,000 compounds and identified 262 small molecules that were predicted to bind the “RVxF”-accommodating cavity of PP1. These compounds were then assayed for inhibition of HIV-1 transcription in CEM T cells. One of the compounds, 1H4, inhibited HIV-1 transcription and replication at non-cytotoxic concentrations. 1H4 prevented PP1-mediated dephosphorylation of a substrate peptide containing an RVxF sequence in vitro. 1H4 also disrupted the association of PP1 with Tat in cultured cells without having an effect on the interaction of PP1 with the cellular regulators, NIPP1 and PNUTS, or on the cellular proteome. Finally, 1H4 prevented the translocation of PP1 to the nucleus. Taken together, our study shows that HIV- inhibition can be achieved through using small molecules to target a non-catalytic site of PP1. This proof-of-principle study can serve as a starting point for the development of novel antiviral drugs that target the interface of HIV-1 viral proteins with their host partners

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

BACKGROUND: High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16(ink4a )drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16(ink4a )overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16(ink4a )overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas METHODS: Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16(ink4a )was analyzed by RT-PCR and by immunohistochemical technique. RESULTS: The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16(ink4a )cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. CONCLUSION: Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective marker of cancer cells with up-regulated expression of p16(ink4a). Our data confirm other previous studies claiming specific p16INK4a up-regulation in the majority of cervical carcinomas at both the protein and mRNA levels. Cytoplasmic accumulation of p16(ink4a )is a feature of cervical carcinomas

In Situ Control of Thermal Activation Conditions by Color for Serpentines with a High Iron Content

Serpentine heat treatment at temperatures of 650–750 °C yields magnesium–silicate reagent with high chemical activity. Precise and express control of roasting conditions in laboratory kilns and industrial aggregates is needed to derive thermally activated serpentines on a large scale. Color change in serpentines with a high iron content during roasting might be used to indicate the changes in chemical activity in the technological process. This study gives a scientific basis for the express control of roasting of such serpentines by comparing the colors of the obtained material and the reference sample. Serpentines with different chemical activity were studied by X-ray diffraction, Mössbauer spectroscopy, and optical spectroscopy. The color parameters were determined using RGB (red, green, blue), CIELAB (International Commission on Illumination 1976 L*a*b), and HSB (hue, brightness, saturation) color models. The color of heat-treated samples was found to be affected by changes in the crystallochemical characteristics of iron included in the structure of the serpentine minerals. The color characteristics given by the CIELAB model were in good coherence with the acid-neutralizing ability and optical spectra of heat-treated serpentines. Thus, in contrast to the long-term analysis by these methods, the control by color palette provides an express assessment of the quality of the resulting product

Magnesium Silicate Binding Materials Formed from Heat-Treated Serpentine-Group Minerals and Aqueous Solutions: Structural Features, Acid-Neutralizing Capacity, and Strength Properties

The influence of structural features of three serpentine-group minerals (antigorite, chrysotile, and lizardite) on the hydration of heat-treated materials and the formation of magnesium silicate binder has been studied. Initial serpentine samples have been fired in the interval 550–800 °C with a step of 50 °C; acid neutralization capacity (ANC) values have been determined for all samples. Antigorite samples (SAP) have exhibited a maximum reactivity at a temperature of 700 °C (ANC 7.7 meq/g). We have established that the acid-neutralizing capacity of chrysotile and lizardite samples in the temperature range of 650–700 °C differ slightly; the capacity varied in the interval of 19.6–19.7 meq/g and 19.6–19.7 meq/g, respectively. The samples obtained at optimal temperatures (antigorite—700 °C, lizardite, and chrysotile—650 °C) have been studied. Heat-treated serpentines have interacted with water vapor for a year; serpentine hydration has been investigated. The strength characteristics of the resulting binder agents were studied after 7, 28, 180, and 360 days. Upon hardening within 7 days, the strengths of the SAP and SCH samples have been almost the same (2.2 MPa), whereas this indicator for the SLH and SLK samples has been significantly lower (0.5 MPa). After hardening for over a year, the chrysotile sample SCH had the highest strength (about 8 MPa), whereas the strength of antigorite SAP was 3 MPa. The samples of initial, heat-treated, and hydrated heat-treated serpentines have been studied using XRD, differential scanning calorimetry, and surface texture analysis. The serpentine structure is crucial in destroying the mineral crystal lattice during heat treatment. In contrast to heat-treated chrysotile and lizardite, antigorite did not adsorb water. Structural features of chrysotile provided the highest compressive strength of the binding agent compared with antigorite and lizardite. The acid-neutralizing ability of lizardite was noticeably higher than antigorite, whereas its compressive strength was lower due to the layered mineral structure and impurities. We have established that the minerals’ structural features are crucial for the hydration of heat-treated serpentines; the structure determines material utilization in various environmental technologies

A 12-mer Peptide of Tag7 (PGLYRP1) Forms a Cytotoxic Complex with Hsp70 and Inhibits TNF-Alpha Induced Cell Death

Investigation of interactions between a pro-inflammatory cytokine tumor necrosis factor (TNFα) and its receptor is required for the development of new treatments for autoimmune diseases associated with the adverse effects of TNFα. Earlier, we demonstrated that the innate immunity protein Tag7 (PGRP-S, PGLYRP1) can interact with the TNFα receptor, TNFR1, and block the transduction of apoptotic signals through this receptor. A complex formed between the Tag7 protein and the major heat shock protein Hsp70 can activate TNFR1 receptor and induce tumor cell death via either apoptotic or necroptotic pathway. In this study, we show that a 12-mer peptide, designated 17.1, which was derived from the Tag7 protein, can be regarded as a novel TNFα inhibitor, also is able to form a cytotoxic complex with the heat shock protein Hsp70. This finding demonstrates a new role for Hsp70 protein in the immune response. Also, this new inhibitory 17.1 peptide demonstrates an anti-inflammatory activity in the complete Freund’s adjuvant (CFA)-induced autoimmune arthritis model in laboratory mice. It appears that the 17.1 peptide could potentially be used as an anti-inflammatory agent

Facile Synthesis of Stable Cerium Dioxide Sols in Nonpolar Solvents

A method is proposed for the preparation of stable sols of nanocrystalline cerium dioxide in nonpolar solvents, based on surface modification of CeO2 nanoparticles obtained by thermal hydrolysis of concentrated aqueous solutions of ammonium cerium(IV) nitrate with residues of 2-ethylhexanoic and octanoic acids. The synthesis was carried out at temperatures below 100 °C and did not require the use of expensive and toxic reagents. An assessment of the radical-scavenging properties of the obtained sols using the superoxide anion-radical neutralization model revealed that they demonstrate notable antioxidant activity. The results obtained indicate the potential of the nanoscale cerium dioxide sols in nonpolar solvents to be used for creating nanobiomaterials possessing antioxidant properties