Systematic Bias In Baroclinic Energy Estimates In Shelf Seas

A simple model of an internal wave advected by an oscillating barotropic flow suggests flaws in standard approaches to estimating properties of the internal tide. When the M2 barotropic tidal current amplitude is of similar size to the phase speed of the M2 baroclinic tide, spectral and harmonic analysis techniques lead to erroneous estimates of the amplitude, phase, and energy in the M2 internal tide. In general, harmonic fits and bandpass or low-pass filters that attempt to isolate the lowest M2 harmonic significantly underestimate the strength of M2 baroclinic energy fluxes in shelf seas. Baroclinic energy flux estimates may show artificial spatial variability, giving the illusion of sources and sinks of energy where none are actually present. Analysis of previously published estimates of baroclinic energy fluxes in the Celtic Sea suggests this mechanism may lead to values being 25%–60% too low

Effects of Cardiac Structural Remodelling During Heart Failure on Cardiac Excitation – Insights from a Heterogeneous 3D Model of the Rabbit Atria

Heart failure is a leading cause of morbidity and mortality in the western world. One of the effects of heart failure is the structural remodelling of cardiac tissue, including tissue dilation and development of fibrosis. It is therefore important to study these changes and their effect on cardiac activity, in order to gain a better understanding of the underlying mechanisms in arrhythmogenesis, which will hopefully enable us to develop better treatments for heart failure. In this study we developed biophysically detailed models of the rabbit atria for normal and heart failure conditions. These models were used to study the effects of structural remodelling of heart failure on cardiac excitation wave conduction. Anatomical reconstructions of the control and heart failure hearts were based on contrast enhanced micro-CT imaging. Fibre orientation was extracted from the control and heart failure datasets. Effects of heart failure geometry on the activation pattern of atrial excitation waves were analyzed. It was found that atrial activation time increased from the control to the heart failure case in both isotropic and anisotropic conditions, which is attributed primarily to the dilation of tissue caused by heart failure

Sedimentary geology of the Middle Carboniferous of the Donbas region (Dniepr-Donets basin, Ukraine)

Peer reviewedPublisher PD

Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.

BackgroundSipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting.MethodsPatients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order.ResultsOf the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation.ConclusionsThis study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment

Storms modify baroclinic energy fluxes in a seasonally stratified shelf sea: inertial-tidal interaction

Observations made near the Celtic Sea shelf edge are used to investigate the interaction between wind-generated near-inertial oscillations and the semidiurnal internal tide. Linear, baroclinic energy fluxes within the near-inertial (f) and semidiurnal (M2) wave bands are calculated from measurements of velocity and density structure at two moorings located 40 km from the internal tidal generation zone. Over the 2 week deployment period, the semidiurnal tide drove 28–48 W m−1 of energy directly on-shelf. Little spring-neap variability could be detected. Horizontal near-inertial energy fluxes were an order of magnitude weaker, but nonlinear interaction between the vertical shear of inertial oscillations and the vertical velocity associated with the semidiurnal internal tide led to a 25–43% increase in positive on-shelf energy flux. The phase relationship between f and M2 determines whether this nonlinear interaction enhances or dampens the linear tidal component of the flux, and introduces a 2 day counter-clockwise beating to the energy transport. Two very clear contrasting regimes of (a) tidally and (b) inertially driven shear and energy flux are captured in the observations

Baroclinic energy flux at the continental shelf edge modified by wind-mixing

Temperature and current measurements from two moorings onshore of the Celtic Sea shelf break, a well-known hot spot for tidal energy conversion, show the impact of passing summer storms on the baroclinic wavefield. Wind-driven vertical mixing changed stratification to permit an increased on-shelf energy transport, and baroclinic energy in the semidiurnal band appeared at the moorings 1–4 days after the storm mixed the upper 50 m of the water column. The timing of the maximum in the baroclinic energy flux is consistent with the propagation of the semidiurnal internal tide from generation sites at the shelf break to the moorings 40 km away. Also, the ∼3 day duration of the peak in M2 baroclinic energy flux at the moorings corresponds to the restratification time scale following the first storm

Electrochemical Dimerization of Phenylpropenoids and the Surprising Antioxidant Activity of the Resultant Quinone Methide Dimers

A simple method for the dimerization of phenylpropenoid derivatives is reported. It leverages electrochemical oxidation of pâ unsaturated phenols to access the dimeric materials in a biomimetic fashion. The mild nature of the transformation provides excellent functional group tolerance, resulting in a unified approach for the synthesis of a range of natural products and related analogues with excellent regiocontrol. The operational simplicity of the method allows for greater efficiency in the synthesis of complex natural products. Interestingly, the quinone methide dimer intermediates are potent radicalâ trapping antioxidants; more so than the phenols from which they are derivedâ or transformed toâ despite the fact that they do not possess a labile Hâ atom for transfer to the peroxyl radicals that propagate autoxidation.Chinonmethidâ Dimere wurden durch milde anodische Oxidation vermittelt durch eine preiswerte und leicht verfügbare Aminbase mit exzellenter Ausbeute und Regiokontrolle hergestellt. Diese Strategie ermöglicht raschen Zugang zu Zwischenprodukten für die katalytische Synthese von Phenylpropenoidâ Oligomeren und bietet ein neues Werkzeug für die Totalsynthese dieser komplexen Moleküle.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146959/1/ange201810870.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146959/2/ange201810870_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146959/3/ange201810870-sup-0001-misc_information.pd

Electrochemical Dimerization of Phenylpropenoids and the Surprising Antioxidant Activity of the Resultant Quinone Methide Dimers

A simple method for the dimerization of phenylpropenoid derivatives is reported. It leverages electrochemical oxidation of pâ unsaturated phenols to access the dimeric materials in a biomimetic fashion. The mild nature of the transformation provides excellent functional group tolerance, resulting in a unified approach for the synthesis of a range of natural products and related analogues with excellent regiocontrol. The operational simplicity of the method allows for greater efficiency in the synthesis of complex natural products. Interestingly, the quinone methide dimer intermediates are potent radicalâ trapping antioxidants; more so than the phenols from which they are derivedâ or transformed toâ despite the fact that they do not possess a labile Hâ atom for transfer to the peroxyl radicals that propagate autoxidation.Quinone methide dimers are prepared via mild anodic oxidation mediated by a cheap and readily available amine base with excellent yield and regiocontrol. This strategy provides rapid access to intermediates for the synthesis of phenylpropenoid oligomers in a catalytic fashion, providing a new tool for the total synthesis of these complex molecules.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147117/1/anie201810870-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147117/2/anie201810870_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147117/3/anie201810870.pd