Perforated tunnel exit regions and micro-pressure waves:geometrical influence

ACKNOWLEDGEMENTS The authors are grateful to the following bodies that provided financial support for the project: (i) China Scholarship Council, (ii) National Natural Science Foundation of China (Grant No. U1334201 and (iii) UK Engineering and Physical Sciences Research Council (Grant No. EP/G069441/1).Peer reviewedPublisher PD

Erratum to: Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma cell lines and biomarkers of response

published_or_final_versionSpringer Open Choice, 01 Dec 201

A narrow line Seyfert 1--blazar composite nucleus in 2MASX J0324+3410

We report the identification of 2MASX J032441.19+341045.9 (hereafter 2MASX J0324+3410) with an appealing object which shows the dual properties of both a narrow line Seyfert 1 galaxy (NLS1) and a blazar. Its optical spectrum, which has a H\beta line width about 1600 km s^-1 (FWHM), an [OIII] to H\beta line ratio ~0.12, and strong FeII emission, clearly fulfills the conventional definition of NLS1s. On the other hand, 2MASX J0324+3410 also exhibits some behavior which is characteristic of blazars, including a flat radio spectrum above 1 GHz, a compact core plus a one-sided jet structure on mas-scale at 8.4 GHz, highly variable fluxes in the radio, optical, and X-ray bands, and a possible detection of TeV gamma-ray emission. On its optical image, obtained with the HST WFPC2, the active nucleus is displaced from the center of the host galaxy, which exhibits an apparent one-armed spiral structure extended to 16 kpc. The remarkable hybrid behavior of this object presents a challenge to current models of NLS1 galaxies and $\gamma$-ray blazars.Comment: 12 pages, 2 figures. Accepted to ApJ

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Crystal Structure of Outer Membrane Protein NMB0315 from Neisseria meningitidis

NMB0315 is an outer membrane protein of Neisseria meningitidis serogroup B (NMB) and a potential candidate for a broad-spectrum vaccine against meningococcal disease. The crystal structure of NMB0315 was solved by single-wavelength anomalous dispersion (SAD) at a resolution of 2.4 Å and revealed to be a lysostaphin-type peptidase of the M23 metallopeptidase family. The overall structure consists of three well-separated domains and has no similarity to any previously published structure. However, only the topology of the carboxyl-terminal domain is highly conserved among members of this family, and this domain is a zinc-dependent catalytic unit. The amino-terminal domain of the structure blocks the substrate binding pocket in the carboxyl-terminal domain, indicating that the wild-type full-length protein is in an inactive conformational state. Our studies improve the understanding of the catalytic mechanism of M23 metallopeptidases

Plasmin Plays an Essential Role in Amplification of Psoriasiform Skin Inflammation in Mice

BACKGROUND: Although increased levels of plasminogen activators have been found in psoriatic lesions, the role of plasmin converted from plasminogen by plasminogen activators in pathogenesis of psoriasis has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: Here we examined the contribution of plasmin to amplification of inflammation in patients with psoriasis. We found that plasminogen was diminished, but that the amount and activity of its converted product plasmin were markedly increased in psoriasis. Moreover, annexin II, a receptor for plasmin was dramatically increased in both dermis and epidermis in psoriasis. Plasmin at sites of inflammation was pro-inflammatory, eliciting production of inflammatory factors, including CC chemokine ligand 20 (CCL20) and interleukin-23 (IL-23), that was mediated by the nuclear factor-kappaB (NF-κB) signaling pathway and that had an essential role in the recruitment and activation of pathogenic C-C chemokine receptor type 6 (CCR6)+ T cells. Moreover, intradermal injection of plasmin or plasmin together with recombinant monocyte/macrophage chemotactic protein-1 (MCP-1) resulted in induction of psoriasiform skin inflammation around the injection sites with several aspects of human psoriasis in mice. CONCLUSIONS/SIGNIFICANCE: Plasmin converted from plasminogen by plasminogen activators plays an essential role in amplification of psoriasiform skin inflammation in mice, and targeting plasmin receptor--annexin II--may harbor therapeutic potential for the treatment of human psoriasis