The role of McmD and the C-terminal of McmD in Methanococcus maripaludis

The minichromosome maintenance (MCM) proteins play an essential role in the replication of DNA, functioning as the genomic helicase in eukaryotes and archaea. In eukaryotes the MCMs comprise a family of six highly related proteins; MCM 2-7, which interact together to form heterohexameric ring complexes. The hexameric structure of MCM contributes to the highly complex and tightly regulated assembly and processivity of the replisome. Significant similarities can be observed between the structure of eukaryotic MCM 2-7 and homologous MCM complexes found in archaea, presenting an intriguing, simplified and biochemically tractable model. The majority of archaeal species have been shown to possess a single functional MCM that forms homohexameric complexes. In previous studies we have discovered that species in the order Methanococcales possess between two and eight MCM genes. Our model organism Methanococcus maripaludis S2 possesses four MCM genes (McmA, B, C & D), which may offer insight into additional motifs required for MCM function. We have generated deletions of individual and combinations of MCM genes, and determined that McmA appears to be essential. Previous studies have shown that McmD may be implicated in DNA damage response and the deletion of McmD causes a DNA damage repair defect. A series of experiments employing UV exposure and ionising radiation as agents of DNA damage were planned, designed to investigate possible roles the protein may play in DNA damage repair. This study was focused around McmD and the insert in the C-terminal of the protein; investigations found that, extrachromosomal overexpression of McmD caused colonies to become sick and possibly caused lethality to cells. Therefore ‘rescue’ of the McmD mutant under a strong constitutive promoter located on plasmid clones (pJB002/pJB003) could not be investigated. McmD gene (MMP1024) and MMP1025 is present in 16 Methanococcales species. MMP1024 and MMP1025 were included in operonic arrangements in 8 of the Methanococcales species analysed. It was possible to produce double and triple M. maripaludis MCM knockout strains (BDΔ, CDΔ, BCΔ, and BCDΔ). For purposes of the domain swap / expression of fusion protein investigation; a clone comprising the N-terminal of McmB and the C-terminal of McmD in commercial expression vector pPROEXHTa was produced. Future work would continue with cloning, co-expression, co-purification of MMP1024 and MMP1025 and biochemical characterisation of McmD

The growth and erosion of cinder cones in Guatemala and El Salvador: Models and statistics

Morphologic data for 147 cinder cones in southern Guatemala andwestern El Salvador are comparedwith data from the San Francisco volcanic field, Arizona (USA), Cima volcanic field, California (USA), Michoácan–Guanajuato volcanic field, Mexico, and the Lamongan volcanic field, East Java. The Guatemala cones have an average height of 110+/-50 m, an average basal diameter of 660+/-230 m and an average top diameter of 180+/-150 m. The generalmorphology of these cones can be described by their average cone angle of slope (24+/-7), average heightto- radius ratio (0.33+/-0.09) and their flatness (0.24+/-0.18). Although the mean values for the Guatemalan cones are similar to those for other volcanic fields (e.g., San Francisco volcanic field, Arizona; Cima volcanic field, California; Michoácan–Guanajuato volcanic field, Mexico; and Lamongan volcanic field, East Java), the range of morphologies encompasses almost all of those observed worldwide for cinder cones. Three new 40Ar/39Ar age dates are combined with 19 previously published dates for cones in Guatemala and El Salvador. There is no indication that the morphologies of these cones have changed over the last 500–1000 ka. Furthermore, a re-analysis of published data for other volcanic fields suggests that only in the Cima volcanic field (of those studied) is there clear evidence of degradation with age. Preliminary results of a numerical model of cinder cone growth are used to show that the range of morphologies observed in the Guatemalan cinder cones could all be primary, that is, due to processes occurring at the time of eruption

Radar array diagnosis from undersampled data using a compressed sensing/sparse recovery technique

A Compressed Sensing/Sparse Recovery approach is adopted in this paper for the accurate diagnosis of fault array elements from undersampled data. Experimental validations on a slotted waveguide test array are discussed to demonstrate the effectiveness of the proposed procedure in the failures retrieval from a small set of measurements with respect to the number of radiating elements. Due to the sparsity feature of the proposed formulation, the method is particularly appealing for the diagnostics of large arrays, typically adopted for radar applications

The growth and erosion of cinder cones in Guatemala and El Salvador: Models and statistics

Morphologic data for 147 cinder cones in southern Guatemala andwestern El Salvador are comparedwith data from the San Francisco volcanic field, Arizona (USA), Cima volcanic field, California (USA), Michoácan–Guanajuato volcanic field, Mexico, and the Lamongan volcanic field, East Java. The Guatemala cones have an average height of 110+/-50 m, an average basal diameter of 660+/-230 m and an average top diameter of 180+/-150 m. The generalmorphology of these cones can be described by their average cone angle of slope (24+/-7), average heightto- radius ratio (0.33+/-0.09) and their flatness (0.24+/-0.18). Although the mean values for the Guatemalan cones are similar to those for other volcanic fields (e.g., San Francisco volcanic field, Arizona; Cima volcanic field, California; Michoácan–Guanajuato volcanic field, Mexico; and Lamongan volcanic field, East Java), the range of morphologies encompasses almost all of those observed worldwide for cinder cones. Three new 40Ar/39Ar age dates are combined with 19 previously published dates for cones in Guatemala and El Salvador. There is no indication that the morphologies of these cones have changed over the last 500–1000 ka. Furthermore, a re-analysis of published data for other volcanic fields suggests that only in the Cima volcanic field (of those studied) is there clear evidence of degradation with age. Preliminary results of a numerical model of cinder cone growth are used to show that the range of morphologies observed in the Guatemalan cinder cones could all be primary, that is, due to processes occurring at the time of eruption

Role of HMGB1 in Cutaneous Melanoma: State of the Art

High-mobility Group Box 1 (HMGB1) is a nuclear protein that plays a key role in acute and chronic inflammation. It has already been studied in several diseases, among them melanoma. Indeed, HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. This research aims to assess the role of this molecule in the pathogenesis of human melanoma and its potential therapeutic role. The research has been conducted on the PubMed database, and the resulting articles are sorted by year of publication, showing an increasing interest in the last five years. The results showed that HMGB1 plays a crucial role in the pathogenesis of skin cancer, prognosis, and therapeutical response to therapy. Traditional therapies target this molecule indirectly, but future perspectives could include the development of new target therapy against HMGB1, thus adding a new approach to the therapy, which has often shown primary and secondary resistance. This could add a new therapy arm which has to be prolonged and specific for each patient

The Magnetic Distortion Calibration System of the LHCb RICH1 Detector

The LHCb RICH1 detector uses hybrid photon detectors (HPDs) as its optical sensors. A calibration system has been constructed to provide corrections for distortions that are primarily due to external magnetic fields. We describe here the system design, construction, operation and performance.Comment: 9 pages, 14 figure

18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy

We investigated whether baseline [F-18] Fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each F-18-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline F-18-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC

Sustained low influenza vaccination in health care workers after H1N1 pandemic: A cross sectional study in an Italian health care setting for at-risk patients

Background: Despite consistent recommendations by all Public Health Authorities in support of annual influenza vaccination for at-risk categories, there is still a low uptake of influenza vaccine in these groups including health care workers (HCWs). Aim of this observational two-phase study was to estimate the immunization rates for influenza in four subsequent seasons and for pandemic H1N1 influenza in HCWs of a University Hospital, and to investigate its distribution pattern and the main determinants of immunization. Phase 1 data collection was performed in 2009-2010, during the peak of H1N1 pandemic. Phase 2 data collection, aimed to investigate seasonal influenza vaccination coverage in the three seasons after pandemic, was performed in 2012-2013. Methods: The overall H1N1 vaccination rate was derived by the Hospital immunization registry. In 2010, the personnel of three Departments (Infectious Diseases, Pediatrics and Gynecology/Obstetrics) completed a survey on influenza. A second-phase analysis was performed in 2012 to investigate influenza vaccination coverage in three consecutive seasons. Results: The first-phase survey showed a low coverage for influenza in all categories (17 %), with the lowest rate in nurses (8.1 %). A total of 37 % of health care workers received H1N1 vaccine, with the highest rate among physicians and the lowest in nurses. H1N1 vaccination was closely related to the Department, being higher in the Department of Infectious Diseases (53.7 %) and Pediatrics (42.4 %) than in Gynecology/Obstetrics (8.3 %). The second-phase survey showed the lowest rate of influenza vaccination in 2012/13 season. The main reasons for not being vaccinated were "Unsure of the efficacy of vaccine" and "Feel not at-risk of getting influenza or its complications". Despite recommendations, influenza vaccine uptake remains poor. Conclusion: Immunization is largely perceived as a personal protection rather than a measure needed to prevent disease spreading to at-risk patients. Compulsory vaccination against influenza should be considered as a possible strategy, at least in health institutions where at-risk patients are admitted