HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status.

BACKGROUND: Antibodies (Abs) to the HPV16 proteome increase risk for HPV-associated OPC (HPVOPC). The goal of this study was to investigate the association of a panel of HPV16 Abs with risk for OPC as well as the association of these Abs with tumor HPV and smoking status among patients with OPC. METHODS: IgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified using a programmable ELISA assay. Sera were obtained from 258 OPC patients at diagnosis and 250 healthy controls. HPV16 tumor status was measured by PCR for 137 cases. Multivariable logistic regression was used to calculate odds ratios for the association of HPV16 Abs with risk for OPC. RESULTS: HPV16 E1, E2, E4, E5, E6, E7 and L1-specific IgG levels were elevated in OPC patients compared to healthy controls (p<0.05). After multivariable adjustment, Ab positivity for NE2, CE2, E6, and/or E7 was associated with OPC risk (OR [95% CI], 249.1 [99.3-624.9]). Among patients with OPC, Ab positivity for these antigens was associated with tumor HPV status, especially among never or light smokers (OR [95% CI], 6.5 [2.1-20.1] and OR [95% CI], 17.5 [4.0-77.2], respectively). CONCLUSIONS: Antibodies to HPV16 proteins are associated with increased risk for HPVOPC. Among patients with OPC, HPV16 Abs are associated with tumor HPV status, in particular among HPV positive patients with no or little smoking history.

The dependence of power consumption of pneumatic conveying systems upon bulk material properties, pipeline bore and routing, and mode of flow

In this paper the dependence of the power consumption of pneumatic conveyors upon conveyed materials, pipeline route and bore, and mode of flow has been examined. The findings are that, with different materials and modes of flow, not only is the amount of power consumed very different but it varies in different ways with pipe bore and routing. Additionally it has been found that, for any given conveying system, the choice of air mover also has a strong influence on the power requirement.

Seasonal dynamics of the carbonate system in the Western English Channel

We present over 900 carbonate system observations collected over four years (2007–2010) in the Western English Channel (WEC). We determined CO2 partial pressure (pCO2), Total Alkalinity (TA) and Dissolved Inorganic Carbon (DIC) along a series of 40 km transects, including two oceanographic stations (L4 and E1) within a sustained coastal observatory. Our data follow a seasonal pattern of CO2 undersaturation from January to August, followed by supersaturation in September–October and a return to near-equilibrium thereafter. This pattern is explained by the interplay of thermal and biological sinks in winter and spring–summer, respectively, followed by the breakdown of stratification and mixing with deeper, high-CO2 water in autumn. The drawdown of DIC and inorganic N between March and June with a C:N ratio of 8.7–9.5 was consistent with carbon over-consumption during phytoplankton growth. Monthly mean surface pCO2 was strongly correlated with depth integrated chlorophyll a highlighting the importance of subsurface chlorophyll a maxima in controlling C-fluxes in shelf seas. Mixing of seawater with riverine freshwater in near-shore samples caused a reduction in TA and the saturation state of calcite minerals, particularly in winter. Our data show that the L4 and E1 oceanographic stations were small, net sinks for atmospheric CO2 over an annual cycle (−0.52±0.66 mol C m−2 y−1 and −0.62±0.49 mol C m−2 y−1, respectively).

THE ROLE OF LIPOPROTEIN(a)/APOLIPOPROTEIN(a) IN ENDOTHELIAL DYSFUNCTION: MECHANISTIC STUDIES IN VASCULAR ENDOTHELIUM

Multiple lines of evidence suggest that elevated plasma lipoprotein(a) (Lp(a)) concentrations are a significant risk factor for the development of a number of vascular diseases including coronary heart disease and stroke. Lp(a) consists of a low-density lipoprotein (LDL)-like moiety and an unique glycoprotein, apolipoprotein(a) (apo(a)), that is covalently attached to the apolipoproteinB-100 (apoB-100) component of LDL by a single disulfide bond. Many studies have suggested a role for Lp(a) in the process of endothelial dysfunction. Indeed, Lp(a) has been shown to increase both the expression of adhesion molecules on endothelial cells (EC), as well as monocyte and leukocyte chemotactic activity in these cells. We have previously demonstrated that Lp(a), through its apo(a) moiety, increases actomyosin-driven EC contraction which, as a consequence, increases EC permeability. In this thesis, we have demonstrated a role for the strong lysine-binding site in the kringle IV type 10 domain of apo(a) in increasing EC permeability, which occurs through a Rho/Rho kinase-dependent pathway. We have further validated these findings using mouse mesenteric arteries in a pressure myograph system. We also have dissected another major signaling pathway initiated by apo(a) that involves in a disruption of adherens junctions in EC. In this pathway, apo(a)/Lp(a) activates the PI3K/Akt/GSK3β-dependent pathway to facilitate nuclear translocation of beta-catenin. In the nucleus beta-catenin induced the expression of cyclooxygenase-2 (COX-2) and the secretion of prostaglandin E2 (PGE2) from the EC. Finally, we have presented data to suggest a novel inflammatory role for apo(a) in which it induces the activation of nuclear factor-kappaB through promotion of the dissociation of IkappaB from the inactive cytoplasmic complex; this allows the nuclear translocation of NFkappaB with attendant effects on the transcription of pro-inflammatory genes. Taken together, our findings may facilitate the development of new drug targets for mitigating the harmful effects of Lp(a) on vascular EC which corresponds to an early step in the process of atherogenesis.

A cephalometric study of class II malocclusions treated with mandibular surgery

INTRODUCTION:

Class II malocclusion is often associated with retrognathic mandible. Some of these problems require surgical correction. The purposes of this study were to investigate treatment outcomes in patients with Class II malocclusions whose treatment included mandibular advancement surgery and to identify predictors of good outcomes.
METHODS:

Pretreatment and posttreatment cephalometric radiographs of 90 patients treated with mandibular advancement surgery by 57 consultant orthodontists in the United Kingdom before September 1998 were digitized, and cephalometric landmarks were identified. Paired samples t tests were used to compare the pretreatment and posttreatment cephalometric values for each patient. For each cephalometric variable, the proportion of patients falling within the ideal range was identified. Multiple logistic regression analysis was performed to identify predictors of achieving ideal range outcomes for the key skeletal (ANB and SNB angles), dental (overjet and overbite), and soft-tissue (Holdaway angle) measurements.
RESULTS:

An overjet within the ideal range of 1 to 4 mm was achieved in 72% of patients and was more likely with larger initial ANB angles. Horizontal correction of the incisor relationship was achieved by a combination of 75% skeletal movement and 25% dentoalveolar change. An ideal posttreatment ANB angle was achieved in 42% of patients and was more likely in females and those with larger pretreatment ANB angles. Ideal soft-tissue Holdaway angles (7 degrees to 14 degrees ) were achieved in 49% of patients and were more likely in females and those with smaller initial SNA angles. Mandibular incisor decompensation was incomplete in 28% of patients and was more likely in females and patients with greater pretreatment mandibular incisor proclination. Correction of increased overbite was generally successful, although anterior open bites were found in 16% of patients at the end of treatment. These patients were more likely to have had initial open bites.
CONCLUSIONS:

Mandibular surgery had a good success rate in normalizing the main dental and skeletal relationships. Less ideal soft-tissue profile outcomes were associated with larger pretreatment SNA-angle values, larger final mandibular incisor inclinations, and smaller final maxillary incisor inclinations. The use of mandibular surgery to correct anterior open bite was associated with poor outcomes.

Electron impact excitation of Ar XVII

Energies for the lowest 49 levels among the 1s(2) and 1snl (n = 2-5) configurations of Ar XVII have been calculated using the GRASP code of Dyall et al. (1989, Comput. Phys. Comm., 55, 424). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Furthermore, collision strengths have also been calculated for all the 1176 transitions among the above 49 levels using the Dirac Atomic R-matrix Code (DARC) of Norrington & Grant (2005, Comput. Phys. Commun., in preparation), over a wide energy range up to 580 Ryd. Resonances have been resolved in the threshold region, and effective collision strengths have been obtained over a wide temperature range up to log T-e = 7.2 K. Comparisons are made with the limited results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 0.1%, whereas results for other parameters are probably accurate to better than 20%.

Energy levels and radiative rates for transitions in Ar XIII, Ar XIV and Ar XV

Energies for 524 levels of Ar XIII, 460 levels of Ar XIV and 156 levels of Ar XV have been calculated using the GRASP code of Dyall et al. (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with the limited results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 1%, whereas results for other parameters are probably accurate to better than 20%. Additionally, the level lifetimes derived from our radiative rates are in excellent agreement with measured values.

Energy levels and transition probabilities for nitrogen-like Fe xx

Energies of the 700 lowest levels in Fe XX have been obtained using the multiconfiguration Dirac-Fock method. Configuration interaction method on the basis set of transformed radial orbitals with variable parameters taking into account relativistic corrections in the Breit-Pauli approximation was used to crosscheck our presented results. Transition probabilities, oscillator and line strengths are presented for electric dipole (E1), electric quadrupole (E2) and magnetic dipole (M1) transitions among these levels. The total radiative transition probabilities from each level are also provided. Results are compared with data compiled by NIST and with other theoretical work.

Relativistic allowed and forbidden transition probabilities for fluorine-like Fe XVIII

Energy levels and the corresponding transition probabilities for allowed and forbidden transitions among the levels of the ground configuration and first 23 excited configurations of fluorine-like Fe XVIII have been calculated using the multiconfigurational Dirac-Fock GRASP code. A total of 379 lowest bound levels of Fe XVIII is presented, and the energy levels are identified in spectroscopic notations. Transition probabilities, oscillator strengths and line strengths for electric dipole (E1), electric quadrupole (E2) and magnetic dipole (M1) transitions among these 379 levels are also presented. The calculated energy levels and transition probabilities are compared with experimental data.

Energy levels and radiative rates for Li-like Ar XVI and Fe XXIV

Energy levels for transitions among the lowest 24 fine- structure levels belonging to the 1s(2)nl(n greater than or equal to 5) configurations of Li-like Ar XVI and Fe XXIV have been calculated using the fully relativistic GRASP code. Oscillator strengths, radiative rates and line strengths have also been generated among these levels for the four types of transitions: electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2). Comparisons are made for the electric dipole transitions with other available results, and the accuracy of the present data is assessed.

Cox-2 Promotes Chromogranin A Expression and Bioactivity: Evidence for a PGE2-Dependent Mechanism and the Involvement of a Proximal cAMP-Responsive Element.

Abstract The prostanoid biosynthetic enzyme cyclooxygenase-2 (Cox-2) is upregulated in several neuroendocrine tumors. The aim of the current study was to employ a neuroendocrine cell (PC12) model of Cox-2 over-expression to identify gene products that might be implicated in the oncogenic and/or inflammatory actions of this enzyme in the setting of neuroendocrine neoplasia. Expression array and real-time PCR analysis demonstrated that levels of the neuroendocrine marker chromogranin A (CGA) were 2-fold and 3.2-fold higher, respectively, in Cox-2 over-expressing cells (PCXII) vs their control (PCMT) counterparts. Immunocytochemical and immunoblotting analyses confirmed that both intracellular and secreted levels of CGA were elevated in response to Cox-2 induction. Moreover, exogenous addition of prostaglandin E2 (1u�­M), mimicked this effect in PCMT cells, while treatment of PCXII cells with the Cox-2 selective inhibitor NS-398 (100 nM) reduced CGA expression levels, thereby confirming the biospecificity of this finding. Levels of neurone specific enolase (NSE) were similar in the two cell lines, suggesting that the effect of Cox-2 on CGA expression was specific and not due to a global enhancement of neuroendocrine marker expression/differentiation. Cox-2-dependent CGA upregulation was associated with significantly increased chromaffin granule number and intracellular and secreted levels of dopamine. CGA promoter-driven reporter gene expression studies provided evidence that prostaglandin E2-dependent upregulation required a proximal cAMP-responsive element (CRE; -71 - -64 bp). This study is the first to demonstrate that Cox-2 upregulates both CGA expression and bioactivity in a neuroendocrine cell line and has major implications for the role of this polypeptide in the pathogenesis of neuroendocrine cancers in which Cox-2 is upregulated.

Monocyte-dependent oncostatin M and TNFa synergize to stimulate unopposed matrix metalloproteinase-1/3 secretion from human lung fibroblasts in tuberculosis

Leukocyte-derived matrix metalloproteinases (MMP) are implicated in the tissue destruction characteristic of tuberculosis (TB). The contribution of lung stromal cells to MMP activity in TB is unknown. Oncostatin M (OSM) is an important stimulus to extrapulmonary stromal MMP induction, but its role in regulation of pulmonary MMP secretion or pathophysiology of TB is unknown. We investigated OSM secretion from Mycobacterium tuberculosis (Mtb)-infected human monocytes/macrophages and the networking effects of such OSM on lung fibroblast MMP secretion. Mtb increased monocyte OSM secretion dose dependently in vitro. In vivo tuberculous granulomas immunostained positively for OSM. Further, conditioned media from Mtb-infected monocytes (CoMTb) induced monocyte OSM secretion (670 ± 55 versus 166 ± 14 pg/mL in controls), implicating an autocrine loop. Mtb-induced OSM secretion was prostaglandin (PG) sensitive, and required activation of surface G-protein coupled receptors. OSM induction was ERK MAP kinase dependent, p38-requiring but JNK-independent. OSM synergized with TNF-, a key cytokine in TB granuloma formation, to stimulate pulmonary fibroblast MMP-1/-3 secretion, while suppressing secretion of tissue inhibitors of metalloproteinases-1/-2. In summary, Mtb infection of monocytes results in PG-dependent OSM secretion, which synergizes with TNF- to drive functionally unopposed fibroblast MMP-1/-3 secretion, demonstrating a previously unrecognized role for OSM in TB.

Energy levels, radiative rates, and excitation rates for transitions in OIV

Aims. In this paper we report calculations for energy levels, radiative rates, and excitation rates for transitions in O IV. Methods. The grasp (general-purpose relativistic atomic structure package) and FAC (flexible atomic code) were adopted for calculating energy levels and radiative rates, and the Dirac atomic R-matrix code (DARC) used to determine the excitation rates. Results. Oscillator strengths and radiative rates are reported for all E1, E2, M1, and M2 transitions among the lowest 75 levels of O IV. Additionally, lifetimes are reported for all levels and comparisons made with those available in the literature. Finally, effective collision strengths are reported for all transitions over a wide temperature range below 106 K. Comparisons are made with earlier results and the accuracy of the data is assessed.