Two-dimensional Distributions and Column Densities of Gaseous Molecules in Protoplanetary Disks II

We have investigated the two-dimensional (R,Z) distribution of deuterated molecular species in circumstellar disks around young stellar objects. The abundance ratios between singly deuterated and normal molecules (``D/H ratios'') in disks evolve in a similar way as in molecular clouds. Fractionation is caused by rapid exchange reactions that are exothermic because of energy differences between deuterated and normal species. In the midplane region, where molecules are heavily depleted onto grain surfaces, the D/H ratios of gaseous molecules are higher than at larger heights. The D/H ratios for the vertical column densities of NH3, H2O, and HCO+ are sensitive to the temperature, and decrease significantly with decreasing radial distance for R < 300 AU. The analogous D/H ratios for CH4 and H2CO, on the other hand, are not very sensitive to the temperature in the range (T=10-50 K) we are concerned with, and do not decrease with decreasing R at R > 50 AU. The D/H column-density ratios also depend on disk mass. In a disk with a larger mass, the ratios of deuterated species to normal species are higher, because of heavier depletion of molecules onto grains. In the second part of the paper, we report molecular column densities for disks embedded in ambient cloud gas. Our results suggest that CN and HCO+ can be tracers of gaseous disks, especially if the central object is a strong X-ray source. Our results also suggest that the radial distributions of CN, C2H, HCN, and H2CO may vary among disks depending on the X-ray luminosity of the central star.Comment: 13 page

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error

Saddle point localization of molecular wavefunctions

The quantum mechanical description of isomerization is based on bound eigenstates of the molecular potential energy surface. For the near-minimum regions there is a textbook-based relationship between the potential and eigenenergies. Here we show how the saddle point region that connects the two minima is encoded in the eigenstates of the model quartic potential and in the energy levels of the [H, C, N] potential energy surface. We model the spacing of the eigenenergies with the energy dependent classical oscillation frequency decreasing to zero at the saddle point. The eigenstates with the smallest spacing are localized at the saddle point. The analysis of the HCN???HNC isomerization states shows that the eigenstates with small energy spacing relative to the effective (v1, v3, l) bending potentials are highly localized in the bending coordinate at the transition state. These spectroscopically detectable states represent a chemical marker of the transition state in the eigenenergy spectrum. The method developed here provides a basis for modeling characteristic patterns in the eigenenergy spectrum of bound states

Scaling and Formulary cross sections for ion-atom impact ionization

The values of ion-atom ionization cross sections are frequently needed for many applications that utilize the propagation of fast ions through matter. When experimental data and theoretical calculations are not available, approximate formulas are frequently used. This paper briefly summarizes the most important theoretical results and approaches to cross section calculations in order to place the discussion in historical perspective and offer a concise introduction to the topic. Based on experimental data and theoretical predictions, a new fit for ionization cross sections is proposed. The range of validity and accuracy of several frequently used approximations (classical trajectory, the Born approximation, and so forth) are discussed using, as examples, the ionization cross sections of hydrogen and helium atoms by various fully stripped ions.Comment: 46 pages, 8 figure

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer

BACKGROUND: G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis. RESULTS: In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I). CONCLUSIONS: These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs

The prognostic relevance of interactions between venous invasion, lymph node involvement and distant metastases in renal cell carcinoma after radical nephrectomy

<p>Abstract</p> <p>Background</p> <p>To investigate a possible prognostic significance of interactions between lymph node invasion (LNI), synchronous distant metastases (SDM), and venous invasion (VI) adjusted for mode of detection, Eastern Cooperative Oncology Group performance status (ECOG PS), erythrocyte sedimentation rate (ESR) and tumour size (TS) in 196 patients with renal cell carcinoma treated with radical nephrectomy.</p> <p>Methods</p> <p>Median follow-up was 5.5 years (mean 6.9 years; range 0.01–19.4). The mode of detection, ECOG PS, ESR and TS were obtained from the patients' records. Vena cava invasion and distant metastases were detected by preoperative imaging. The surgical specimens were examined for pathological stage, LNI and VI.</p> <p>Results</p> <p>The univariate analyses showed significant impact of VI, LNI, SDM, ESR and TS (p < 0.001), as well as mode of detection (p = 0.003) and ECOG PS (p = 0.002) on cancer specific survival. In multivariate analyses LNI was significantly associated with survival only in patients without SDM or VI (p < 0.001) with a hazard ratio of 9.0. LNI lost its prognostic significance when SDM or VI was present.</p> <p>Conclusion</p> <p>Our findings underline the prognostic importance of the status of the lymph nodes. LNI, SDM, ESR, and VI were independently associated with cancer specific survival after radical nephrectomy. LNI provided the strongest prognostic information for patients without SDM or VI whereas SDM and VI had strongest impact on survival when there was no nodal involvement.</p