Formation of polar stratospheric clouds simulated in a two dimensional model of the atmosphere

A microphysics code has been implemented in a two dimensional model of the atmosphere to study formation of polar stratospheric clouds containing HCl or HNO3. The model range is from pole to pole in latitude and from the ground to about 20 km in altitude. Resolution in latitude is 10 deg and about 0.8 km in altitude. This is an Eulerian model with prescribed eddy diffusion coefficients and the circulation obtained from observations. The chemistry of the model follows the family approach for NO(x), Cl(x) and HO(x) while the ozone is fixed and changed seasonally. The aerosol code is based on an assigned population of condensation, coagulation and sedimentation. Aerosol growth is simulated in nine different size bins ranging between 0.01u and 2.56u. The model has been built to study aerosol layers formation in the upper troposphere and lower stratosphere and has been validated for sulfate aerosol resulting from a rather complex sulfur chemistry

Pharmacology and clinical potential of guanylyl cyclase C agonists in the treatment of ulcerative colitis.

Agonists of the transmembrane intestinal receptor guanylyl cyclase C (GCC) have recently attracted interest as promising human therapeutics. Peptide ligands that can specifically induce GCC signaling in the intestine include endogenous hormones guanylin and uroguanylin, diarrheagenic bacterial enterotoxins (ST), and synthetic drugs linaclotide, plecanatide, and SP-333. These agonists bind to GCC at intestinal epithelial surfaces and activate the receptor\u27s intracellular catalytic domain, an event initiating discrete biological responses upon conversion of guanosine-5\u27-triphosphate to cyclic guanosine monophosphate. A principal action of GCC agonists in the colon is the promotion of mucosal homeostasis and its dependent barrier function. Herein, GCC agonists are being developed as new medications to treat inflammatory bowel diseases, pathological conditions characterized by mucosal barrier hyperpermeability, abnormal immune reactions, and chronic local inflammation. This review will present important concepts underlying the pharmacology and therapeutic utility of GCC agonists for patients with ulcerative colitis, one of the most prevalent inflammatory bowel disease disorders

Nuovi Approcci Terapeutici contro il Cancro del Colon

This presentation was given in Augusta (Siracusa, Italy) for the 2004 Paul Harris Fellow Award, Rotary Foundation of Rotary International. The lecture discusses the clinical significance of the GC-C pathway and its potential as a therapeutic target for colon cancer and metastatic tumors. It underscores the importance of the dysregulation of the GC-C pathway in promoting colorectal tumorigenesis and of dietary calcium in the GC-C-mediated chemoprevention. Questa e’ la presentazione per il Premio 2004 Paul Harris Fellow del Rotary International (Augusta, Siracusa, Italia). La dissertazione illustra l’importante significato clinico della via moleculare regulata da GC-C e dai suoi ligandi (guanilina, uroguanilina ed ST) per la prevenzione e cura del cancro del coloretto

Targeting the cGMP Pathway to Treat Colorectal Cancer

This presentation was given in 2009 for the Seminar Series of the Department of Molecular Physiology and Biophysics, Thomas Jefferson University (Philadelphia, PA, USA). It illustrates the role of the calcium-sensing receptor (CaR) and matrix metalloproteinase 9 (MMP-9) as critical downstream mediators of the anticancer GCC pathway in intestine. Questa presentazione e’ stata effettuata per il Seminar Series del Dipartimento di Fisiologia Molecolare e Biofisica dell’Universita’ del Thomas Jefferson (Filadelfia, USA). La presentazione illustra l’importante ruolo del CaR ed MMP-9 come mediatori della soppressione del processo tumorale dell’intestino da parte del recettore GCC

Guanylyl Cyclase C (GC-C) Inhibits Human Colon Carcinoma Cell Growth

This is the presentation given for the 2001 Presidential Trainee Young Investigator Award, American Society for Clinical Pharmacology and Therapeutics. An abstract of the presentation has been published in Clin. Pharmacol. Ther., 69(2):P62, 2001. The presentation illustrates the role of the intestinal GC-C receptor as a negative regulator of cell proliferation and cell cycle kinetics in colorectal cancer. It suggests that paracrine GC-C hormones guanylin/uroguanylin are physiological inducers of the proliferation-to-differentiation transition along the intestinal crypt-villus axis. Importantly, the bacterial enterotoxin ST, a potent exogenous GC-C agonist, is offered as a potential cytostatic agent for the prevention and treatment of colorectal cancer in patients. Questa presentazione e’ stata effettuata in occasione del Premio 2001 Presidential Trainee Young Investigator della Societa’ Americana di Farmacologia e Terapia Clinica. La presentazione suggerisce per la prima volta che il recettore intestinale guanilato ciclasi C (GC-C o GCC) ed i suoi ligandi (guanilina, uroguanilina, ST) sono regolatori citostatici della proliferazione delle cellule intestinali, che possono essere utilizzati per la prevenzione e cura del cancro del coloretto

Upper tropospheric ice sensitivity to sulfate geoengineering

Abstract. Aside from the direct surface cooling that sulfate geoengineering (SG) would produce, investigations of the possible side effects of this method are still ongoing, such as the exploration of the effect that SG may have on upper tropospheric cirrus cloudiness. The goal of the present study is to better understand the SG thermodynamical effects on the freezing mechanisms leading to ice particle formation. This is undertaken by comparing SG model simulations against a Representative Concentration Pathway 4.5 (RCP4.5) reference case. In the first case, the aerosol-driven surface cooling is included and coupled to the stratospheric warming resulting from the aerosol absorption of terrestrial and solar near-infrared radiation. In a second SG perturbed case, the surface temperatures are kept unchanged with respect to the reference RCP4.5 case. When combined, surface cooling and lower stratospheric warming tend to stabilize the atmosphere, which decreases the turbulence and updraft velocities (−10 % in our modeling study). The net effect is an induced cirrus thinning, which may then produce a significant indirect negative radiative forcing (RF). This RF would go in the same direction as the direct effect of solar radiation scattering by aerosols, and would consequently influence the amount of sulfur needed to counteract the positive RF due to greenhouse gases. In our study, given an 8 Tg-SO2 yr−1 equatorial injection into the lower stratosphere, an all-sky net tropopause RF of −1.46 W m−2 is calculated, of which −0.3 W m−2 (20 %) is from the indirect effect on cirrus thinning (6 % reduction in ice optical depth). When surface cooling is ignored, the ice optical depth reduction is lowered to 3 %, with an all-sky net tropopause RF of −1.4 W m−2, of which −0.14 W m−2 (10 %) is from cirrus thinning. Relative to the clear-sky net tropopause RF due to SG aerosols (−2.1 W m−2), the cumulative effect of the background clouds and cirrus thinning accounts for +0.6 W m−2, due to the partial compensation of large positive shortwave (+1.6 W m−2) and negative longwave adjustments (−1.0 W m−2). When surface cooling is ignored, the net cloud adjustment becomes +0.8 W m−2, with the shortwave contribution (+1.5 W m−2) almost twice as much as that of the longwave (−0.7 W m−2). This highlights the importance of including all of the dynamical feedbacks of SG aerosols

Tumor Epithelial Cell Matrix Metalloproteinase 9 (MMP-9) is a Prognostic Marker in Colorectal Cancer

Presented at American Association Cancer Research in 2008 Zuzga D.S., Gibbons A.V., Li P., Lubbe W.J., Chervoneva I., Pitari G.M. “Tumor epithelial cell MMP-9 is a prognostic marker in colorectal cancer”. In: American Association for Cancer Research Special Conference, Molecular Diagnostics in Cancer Therapeutic Development: Proceedings; 2008 Sept 22-25; Philadelphia, PA. Abstract A40. Colorectal cancer is the second leading cause of cancer-related mortality indeveloped nations. Mortality from colon cancer largely reflects metastasis, thespread of the disease to distant sites. Early diagnosis of pre-metastatic diseaseand accurate stratification of patients with metastasis is pivotal to decreasemortality rates from colon cancer by effectively administering surgery alone orwith chemotherapy. However, specific pathological markers of colorectal cancermetastasis have not emerged. Matrix metalloproteinase 9 (MMP-9) is a keyregulator of metastasis and a therapeutic target in colon cancer. Here, MMP-9overexpression in pure tumor epithelial, but nor stromal, cell populations frompatients was associated with metastatic colorectal cancer progression as definedby RT-PCR and confirmed by immunostaining. Thus, tumors with increasedMMP-9 expression compared to matched normal adjacent tissues alwaysexhibited metastatic dissemination. In particular, MMP-9 overexpression in tumorepithelial cells, compared to normal epithelial cells, specifically predicted lymphnode involvement. Importantly, patients with relative increase of MMP-9 levels intumor epithelial cells were characterized by more advanced disease stages, withsignificantly higher proportion of regional lymph nodes harboring metastasis,compared to patients with a relative decrease in MMP-9 expression. Together,these observations suggest tumor epithelial cell MMP-9 is a novel prognosticmarker that may be exploited for more efficient disease stage stratification andtherapeutic regimen selection in patients with colorectal cancer

Sulfate Aerosols from Non-Explosive Volcanoes: Chemical-Radiative Effects in the Troposphere and Lower Stratosphere

SO2 and H2S are the two most important gas-phase sulfur species emitted by volcanoes, with a global amount from non-explosive emissions of the order 10 Tg-S/yr. These gases are readily oxidized forming SO42− aerosols, which effectively scatter the incoming solar radiation and cool the surface. They also perturb atmospheric chemistry by enhancing the NOx to HNO3 heterogeneous conversion via hydrolysis on the aerosol surface of N2O5 and Br-Cl nitrates. This reduces formation of tropospheric O3 and the OH to HO2 ratio, thus limiting the oxidation of CH4 and increasing its lifetime. In addition to this tropospheric chemistry perturbation, there is also an impact on the NOx heterogeneous chemistry in the lower stratosphere, due to vertical transport of volcanic SO2 up to the tropical tropopause layer. Furthermore, the stratospheric O3 formation and loss, as well as the NOx budget, may be slightly affected by the additional amount of upward diffused solar radiation and consequent increase of photolysis rates. Two multi-decadal time-slice runs of a climate-chemistry-aerosol model have been designed for studying these chemical-radiative effects. A tropopause mean global net radiative flux change (RF) of −0.23 W·m−2 is calculated (including direct and indirect aerosol effects) with a 14% increase of the global mean sulfate aerosol optical depth. A 5–15 ppt NOx decrease is found in the mid-troposphere subtropics and mid-latitudes and also from pole to pole in the lower stratosphere. The tropospheric NOx perturbation triggers a column O3 decrease of 0.5–1.5 DU and a 1.1% increase of the CH4 lifetime. The surface cooling induced by solar radiation scattering by the volcanic aerosols induces a tropospheric stabilization with reduced updraft velocities that produce ice supersaturation conditions in the upper troposphere. A global mean 0.9% decrease of the cirrus ice optical depth is calculated with an indirect RF of −0.08 W·m−2

Impact of Stratospheric Volcanic Aerosols on Age-of-Air and Transport of Long-Lived Species

The radiative perturbation associated to stratospheric aerosols from major explosive volcanic eruptions may induce significant changes in stratospheric dynamics. The aerosol heating rates warm up the lower stratosphere and cause a westerly wind anomaly, with additional tropical upwelling. Large scale transport of stratospheric trace species may be perturbed as a consequence of this intensified Brewer–Dobson circulation. The radiatively forced changes of the stratospheric circulation during the first two years after the eruption of Mt. Pinatubo (June 1991) may help explain the observed trend decline of long-lived greenhouse gases at surface stations (approximately −8 and −0.4 ppbv/year for CH4 and N2O, respectively). This decline is partly driven by the increased mid- to high-latitude downward flux at the tropopause and also by an increased isolation of the tropical pipe in the vertical layer near the tropopause, with reduced horizontal eddy mixing. Results from a climate-chemistry coupled model are shown for both long-lived trace species and the stratospheric age-of-air. The latter results to be younger by approximately 0.5 year at 30 hPa for 3–4 years after the June 1991 Pinatubo eruption, as a result of the volcanic aerosols radiative perturbation and is consistent with independent estimates based on long time series of in situ profile measurements of SF6 and CO2. Younger age of air is also calculated after Agung, El Chichon and Ruiz eruptions, as well as negative anomalies of the N2O growth rate at the extratropical tropopause layer. This type of analysis is made comparing the results of two ensembles of model simulations (1960–2005), one including stratospheric volcanic aerosols and their radiative interactions and a reference case where the volcanic aerosols do not interact with solar and planetary radiation