ArcTiCA: Arctic tidal constituents atlas.

Tides in the Arctic Ocean affect ocean circulation and mixing, and sea ice dynamics and thermodynamics. However, there is a limited network of available in situ tidal coefficient data for understanding tidal variability in the Arctic Ocean; e.g., the global TICON-3 database contains only 111 sites above 60°N and 21 above 70°N. At the same time, the presence of sea ice and latitude limits of satellite altimetry complicate altimetry-based retrievals of Arctic tidal coefficients. This leads to a reliance on ocean tide models whose accuracy depend on having sufficient in situ data for validation and assimilation. Here, we present a comprehensive new dataset of tidal constituents in the Arctic region, combining analyses of in situ measurements from tide gauges, ocean bottom pressure sensors and GNSS interferometric reflectometry. The new dataset contains 914 measurement sites above 60°N and 399 above 70°N, with each site being quality-assessed and expert guidance provided to help maximise the usage of the dataset. We also compare the dataset to recent tide models.

Developmental Manganese Exposure Causes Lasting Attention Deficits Accompanied by Dysregulation of mTOR Signaling and Catecholaminergic Gene Expression in Brain Prefrontal Cortex.

Elevated manganese (Mn) exposure is associated with attentional deficits in children, and is an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn exposure causes lasting attention and sensorimotor deficits in a rat model of early childhood Mn exposure, and that these deficits are associated with a hypofunctioning catecholaminergic system in the prefrontal cortex (PFC), though the mechanistic basis for these deficits is not well understood. To address this, male Long-Evans rats were exposed orally to Mn (50 mg/kg/d) over PND 1-21 and attentional function was assessed in adulthood using the 5-Choice Serial Reaction Time Task. Targeted catecholaminergic system and epigenetic gene expression, followed by unbiased differential DNA methylation and gene regulation expression transcriptomics in the PFC, were performed in young adult littermates. Results show that developmental Mn exposure causes lasting focused attention deficits that are associated with reduced gene expression of tyrosine hydroxylase, dopamine transporter, and DNA methyltransferase 3a. Further, developmental Mn exposure causes broader lasting methylation and gene expression dysregulation associated with epigenetic regulation, inflammation, cell development, and hypofunctioning catecholaminergic neuronal systems. Pathway enrichment analyses uncovered mTOR and Wnt signaling pathway genes as significant transcriptomic regulators of the Mn altered transcriptome, and Western blot of total, C1 and C2 phospho-mTOR confirmed mTOR pathway dysregulation. Our findings deepen our understanding of the mechanistic basis of how developmental Mn exposure leads to lasting catecholaminergic dysfunction and attention deficits, which may aid future therapeutic interventions of environmental exposure associated disorders. Significance Statement: Attention deficit hyperactivity disorder (ADHD) is associated with environmental risk factors, including exposure to neurotoxic agents. Here we used a rodent model of developmental manganese (Mn) exposure producing lasting attention deficits to show broad epigenetic and gene expression changes in the prefrontal cortex, and to identify disrupted mTOR and Wnt signaling pathways as a novel mechanism for how developmental Mn exposure may induce lasting attention and catecholaminergic system impairments. Importantly, our findings establish early development as a critical period of susceptibility to lasting deficits in attentional function caused by elevated environmental toxicant exposure. Given that environmental health threats disproportionately impact communities of color and low socioeconomic status, our findings can aid future studies to assess therapeutic interventions for vulnerable populations.

Factors associated with prolonged length of stay for elective hepatobiliary and neurosurgery patients: a retrospective medical record review.

BACKGROUND: Patients with prolonged length of hospital stay (LOS) not only increase their risks of nosocomial infections but also deny other patients access to inpatient care. Hepatobiliary (HPB) malignancies have some of highest incidences in East and Southeast Asia and the management of patients undergoing HPB surgeries have yet to be standardized. With improved neurosurgery techniques for intracranial aneurysms and tumors, neurosurgeries (NS) can be expected to increase. Elective surgeries account for far more operations than emergencies surgeries. Thus, with potentially increased numbers of elective HPB and NS, this study seeks to explore perioperative factors associated with prolonged LOS for these patients to improve safety and quality of practice. METHODS: A retrospective cross-sectional medical record review study from January 2014 to January 2015 was conducted at a 1250-bed tertiary academic hospital in Singapore. All elective HPB and NS patients over 18 years old were included in the study except day and emergency surgeries, resulting in 150 and 166 patients respectively. Prolonged LOS was defined as above median LOS based on the complexity of the surgical procedure. The predictor variables were preoperative, intraoperative, and postoperative factors. Student's t-test and stepwise logistic regression analyses were conducted to determine which factors were associated with prolonged LOS. RESULTS: Factors associated with prolonged LOS for the HPB sample were age and admission after 5 pm but for the NS sample, they were functional status, referral to occupational therapy, and the number of hospital-acquired infections. CONCLUSION: Our findings indicate that preoperative factors had the greatest association with prolonged LOS for HPB and NS elective surgeries even after adjusting for surgical complexity, suggesting that patient safety and quality of care may be improved with better pre-surgery patient preparation and admission practices.

Triple quadrupole mass spectrometry as applied to flame diagnostics: study of the C2H 4/N 2O/Ar flame.

A recently developed research apparatus for characterization of low-pressure premixed flames has been developed and was used to characterize the C2H4/N2O/Ar flame at 20 torr. This instrument incorporates several diagnostic techniques in one apparatus so that individual techniques can be quantitatively compared and the usable detection range (both in terms of resolution and species detection) expanded. Results discussed in this report include mass analysis by triple quadrupole mass spectrometer and temperature measurement by thermocouple. Concentration profiles in the one-dimensional flame include CO, N2, and C2H4, at nominal m/z 28 as well as CO2 and N2O at m/z 44.

Characterization of calcium-independent forms of protein kinase C-beta in phorbol ester-treated rabbit platelets.

The subcellular distribution, size, and activation state of protein kinase C (PKC) were studied after short term exposure of rabbit platelets to a saturating dose of 12-O-tetradecanoylphorbol 13-acetate (TPA). Cytosolic and Nonidet P-40-solubilized particulate extracts prepared from TPA-treated platelets were subjected to analytical column chromatography on Mono Q, hydroxylapatite, and Superose 6/12. PKC activity was assayed according to the ability of the enzyme to phosphorylate (i) histone H1 in the presence of the activators calcium, diacylglycerol, and phosphatidylserine; (ii) histone H1 after proteolytic activation of PKC with trypsin; and (iii) protamine in the absence of calcium and lipid. Within 1 min of TPA treatment of platelets, greater than 95% of the PKC activity was particulate associated, as assessed by all three methods. The particulate PKC activity from 1-min TPA-treated cells eluted from Mono Q with approximately 0.35 M NaCl (peak I), and it was highly dependent upon Ca2+ and lipid for optimal histone H1 phosphorylation. With longer exposure times of platelets to TPA, the disappearance of the Mono Q peak I form of PKC was correlated with the production of new PKC species that were released from Mono Q with approximately 0.4 M NaCl (peak II), approximately 0.5 M NaCl (peak III), and approximately 0.6 M NaCl (peak IV). These last forms of PKC were still lipid activated but exhibited little Ca2+ dependence. The Mono Q peak III form displayed a particularly high level of histone H1 phosphorylating activity in the absence of lipid and Ca2+. All of these forms behaved as approximately 65-kDa proteins on Superose 6/12, but on sodium dodecyl sulfate-polyacrylamide gels, Western blotting with anti-PKC-beta antibodies revealed immunoreactive polypeptides of approximately 79 kDa (Mono Q peaks I, II, and IV) and approximately 100-kDa (Mono Q peak III). Hydroxylapatite column chromatography permitted partial resolution of the Mono Q peaks I and II forms, which were eluted within a concentration range of potassium phosphate (100-150 mM) which was typical of the beta isozyme of PKC. Treatment of the Mono Q peak III and IV PKC forms with alkaline phosphatase resulted in the production of the peak I form, which implicated protein phosphorylation in the interconversion of the various PKC forms.

A high transmission hemispherical energy analyzer for ion spectrometry.

A hemispherical energy analyzer was constructed by using a novel approach to control the fringing electrostatic field. It provides several properties useful in ion spectrometers: namely, rather simple fabrication and compact size, high transmission efficiency at moderate resolution, and the capability to adjust resolution by changing the intersphere potentials. A computer program was developed to evaluate ion trajectories through the hemispherical analyzer. Data obtained from the trajectories were used to predict the characteristics of the analyzer. Experiments performed to determine the kinetic energy dependence of the absolute transmission and the resolution functions are in accord with theoretical calculations.

Erbstatin blocks platelet activating factor-induced protein-tyrosine phosphorylation, polyphosphoinositide hydrolysis, protein kinase C activation, serotonin secretion and aggregation of rabbit platelets.

The role of protein-tyrosine phosphorylation in the signal transduction of platelet activating factor (PAF) was investigated in rabbit platelets with a range of synthetic compounds that inhibit protein-tyrosine kinases. In particular, erbstatin (IC50 approximately 20 micrograms/ml) abrogated a wide range of platelet responses to PAF, including tyrosine phosphorylation of cellular proteins, polyphosphoinositide turnover, activation of membranous protein kinase C, platelet aggregation, and serotonin secretion. With about a third of the potency of erbstatin, compound RG50864 also inhibited many of these responses, whereas at 100 micrograms/ml, genistein, 670C88 and ST271 were without effect. Finally, the ability of thrombin to cause platelet aggregation and serotonin secretion was also compromised by erbstatin.

Protein kinase C activation by platelet-activating factor is independent of enzyme translocation.

The subcellular distribution and activation state of protein kinase C (PKC) was studied after short-term exposure of rabbit platelets to platelet-activating factor (PAF). Cytosolic and nonidet P-40-solubilized particulate extracts prepared from treated platelets were subjected to analytical column chromatography on MonoQ, hydroxylapatite and Superose 6/12. PKC activity was assayed by the ability of the enzyme to phosphorylate the following substrates: (i) histone H1 in the presence of the activators calcium, diacylglycerol and phosphatidylserine; (ii) histone H1 following proteolytic activation of PKC with 0.5 micrograms trypsin/ml; and (iii) protamine in the absence of calcium and lipid. PAF treatment for 1-20 min elicited a rapid 2-4-fold activation of both cytosolic and particulate-derived PKC as assessed by all three methods. On the other hand, there were no significant PAF-induced changes in the level of [3H]phorbol-12,13-dibutyrate binding by soluble and particulate-associated PKC. Hydroxyapatite column chromatography revealed that in non-treated rabbit platelets the type II (beta) form of PKC predominated, but PAF appeared to induce a shift in the elution profile from this resin. The stability of the PAF activation of PKC to column chromatography and the altered binding affinity to hydroxylapatite indicated that the stimulation might be a consequence of covalent modification, albeit minor, since PKC still eluted as an 80 kDa protein from Superose 6/12. As the PAF-induced increases in the kinase activity of PKC were preserved even after proteolytic activation with trypsin, but were without effect on the phorbol ester binding activity, such a putative modification may have occurred within or near the catalytic domain of PKC. These findings imply that PAF may directly modulate the activity of preexisting membrane-associated PKC by a novel mechanism, rather than by eliciting its recruitment from the cytoplasm.

Carboxyglutamic acid (Gla) containing proteins of human calcified atherosclerotic plaque solubilized by EDTA. Molecular weight distribution and relationship to osteocalcin.

Proteins containing the calcium binding amino acid, gamma-carboxyglutamic acid (Gla), are abundant in calcified human atherosclerotic plaque, but are detectable only at trace levels in the normal arterial wall and non-mineralized atherosclerotic lesions. These proteins have been incompletely characterized, and their role in the pathophysiology of atherosclerosis is not known. The present study sought to determine the overall molecular weight distribution of the calcified plaque Gla-protein fraction solubilized by EDTA demineralization and the possible relationship of these proteins to the bone Gla-protein, osteocalcin. Calcified atheromata were demineralized with EDTA (0.5 M, pH 6.9) for 7 days and the dialyzed EDTA extract subjected to procedures which specifically labeled the protein-bound Gla-residues with tritium. The EDTA solubilized Gla-protein fraction (19.5% of the total Gla) was separated by gel filtration high performance liquid chromatography which demonstrated a single broad radiolabeled Gla-protein peak with an approximate molecular weight of 6000 daltons. In addition the EDTA solubilized atherosclerotic Gla-proteins could be distinguished from the bone Gla-protein, osteocalcin (molecular weight = 5700 daltons), by reverse phase HPLC and specific radioimmunoassays for osteocalcin. It is concluded that the Gla-proteins of human calcified atherosclerotic plaque solubilized with EDTA demineralization consist of a heterogeneous 6000 dalton fraction, which is apparently unrelated to the bone Gla-protein, osteocalcin.

Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats.

Bioprosthetic cardiac valve calcification is a frequent complication after long-term valve replacement. In this study the authors sought to examine the biologic determinants of this type of dystrophic calcification using subcutaneous implants of glutaraldehyde-preserved porcine aortic valve leaflets (GPVs) in rats. GPVs and clinical valvular bioprostheses were prepared identically. Retrieved implants were examined for calcification and the deposition of osteocalcin (OC), a vitamin K-dependent, bone-derived protein, that is found in other dystrophic and ectopic calcifications. GPVs implanted in 3-week-old rats calcified progressively (GPV Ca2+, 122.9 +/- 6.0 micrograms/mg) after 21 days, with mineral deposition occurring in a morphologic pattern comparable to that noted in clinical retrievals. Calcified GPVs accumulated osteocalcin (OC, 183.4 +/- 19.4 ng/mg); Nonpreserved porcine aortic leaflet implants did not calcify (Ca2+ + 5.6 +/- 1.0 micrograms/mg). Millipore diffusion chamber (0.45-mu pore size enclosed GPV implants accumulated calcium and adsorbed osteocalcin despite the absence of attached host cells. GPVs implanted for 21 days in 8-month-old rats calcified less (GPV Ca2+, 22.4 +/- 5.0 micrograms/mg) than did GPVs implanted in 3-week-old rats (see above). High-dose warfarin therapy (80 mg/kg) did not alter GPV calcification (GPV Ca2+, 39.6 +/- 2.9 micrograms/mg) in 72-hour subcutaneous implants in 3-week-old male rats, compared with control rats (GPV Ca2+, 40.8 +/- 4.8 micrograms/mg).

Mechanism of calcification of porcine bioprosthetic aortic valve cusps: role of T-lymphocytes.

Calcification of glutaraldehyde-preserved porcine aortic valve bioprosthetic cusps limits their success as cardiac valve substitutes. Subcutaneous implants of porcine bioprostheses in rats and rabbits have provided a convenient experimental tool to study this calcification process. Previous clinical research has suggested that the host's immune response to the porcine xenograft tissue may contribute to the calcific degeneration. To investigate the possible contribution of the immune response, porcine bioprosthetic cusps implanted subcutaneously in congenitally athymic (nude) BALBc mice and normal controls were analyzed biochemically and histologically after retrieval at 21 days. Calcification was comparable in implants retrieved from athymic (calcium 95.5 +/- 24.5 micrograms/mg) and normal mice (calcium 102.3 +/- 4.66 micrograms/mg). Explants from nude mice demonstrated fewer adherent cells than those from normal animals, but the morphologic characteristics of the calcification were the same in both groups, with dystrophic mineralization of the spongiosa predominating. Thus, normal T-lymphocyte function is not necessary for porcine bioprosthetic calcification, and immunologic processes do not contribute to this process.