Drug design and synthesis of first in class PDZ1 targeting NHERF1 inhibitors as anticancer agents

Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents

Parental species and hybrid descendants of Bacillus (Insecta Phasmatodea) show different patterns of highly amplified, colocalized ribosomal and telomeric sequences

We investigated by dual-color fluorescence in situ hybridization (FISH) with 28S ribosomal and (TTAGG)n telomeric probes all species of the circum-Mediterranean genus Bacillus encompassing bisexual and parthenogenetic taxa, namely the three parental species (B. grandii, B. atticus, B. rossius) and the two derived hybrids (B. whitei, B. lynceorum). Specimens were collected in Italian mainland, Sardinia and Sicily. In all species the presence of colocalized, highly amplified ribosomal and telomeric sequences was demonstrated by the double labelling of the cytological satellites. These satellites varied in size, number and location both among and within species. In B. grandii and B. atticus a maximum of two FISH-labeled locations were observed, whereas in B. rossius and in the two hybrids up to 11 different positions were recorded. Moreover, our investigations showed a significant occurrence of chromosome breakages and rearrangements. The overall meaning of the ribosomal and telomeric sequence colocalization as well as the Nucleolar Organizer Region mobility and activity are discussed in both the ancestors and their hybrid descendants. It is noteworthy that the same trait has been shown in seven additional phasmid species belonging to distantly related genera. This trait could be a shared ancestral character in phasmids

ATLAS RPC Quality Assurance results at INFN Lecce

The main results of the quality assurance tests performed on the Resistive Plate Chamber used by the ATLAS experiment at LHC as muon trigger chambers are reported and discussed. Since July 2004, about 270 RPC units has been certified at INFN Lecce site and delivered to CERN, for being integrated in the final muon station of the ATLAS barrel region. We show the key RPC characteristics which qualify the performance of this detector technology as muon trigger chamber in the harsh LHC enviroments. These are dark current, chamber efficiency, noise rate, gas volume tomography, and gas leakage.Comment: Comments: 6 pages, 1 table, 9 figures Proceedings of XXV Physics in Collision-Prague, Czech Republic, 6-9 July 200

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

Single Event Effects in the Pixel readout chip for BTeV

In future experiments the readout electronics for pixel detectors is required to be resistant to a very high radiation level. In this paper we report on irradiation tests performed on several preFPIX2 prototype pixel readout chips for the BTeV experiment exposed to a 200 MeV proton beam. The prototype chips have been implemented in commercial 0.25 um CMOS processes following radiation tolerant design rules. The results show that this ASIC design tolerates a large total radiation dose, and that radiation induced Single Event Effects occur at a manageable level.Comment: 15 pages, 6 Postscript figure

Use of mixed study techniques in the evaluation of coastline dynamics - the “Porto Cesareo” MPA case of study

In recent decades, the much-discussed climate changes with the consequent variations in sea and weather conditions and the rise of the mean sea level are causing an indisputable set of negative actions on the entire coastal system mainly due to the increase of the erosive phenomenon along the shorelines. These critical scenarios have a major impact even on a local scale, and because of that, we decided to study a well knows tract of rocky/sandy mixed coast, in a highly anthropized area, even if located inside the “Porto Cesareo” Marine Protected Area (MPA) (Ionian Sea, Gulf of Taranto, Puglia Region, Italy). The high naturalistic and archaeological value of this area calls for a greater institutional effort in the study of erosional phenomena. Several historical documents from other studies point out that this coastal area is an ideal place for this kind of research. The effects of coastal erosion and anthropic pressures along this tract of coast require adequate efforts for a consistent and rapid evaluation of the coastal dynamics. The methodologies proposed in this work are based on mixed techniques from different fields of study, integrating recent aero photogrammetry surveys with drones, aerial images acquired by the Italian Military Geographic Institute (IGM), elaboration of paleoshorelines related by underwater archaeological markers and their dating, and finally on the elaboration of satellite products useful for the study of vast areas. The monitoring of coastal areas and the evaluation of shoreline dynamics are core topics in the implementation of managing actions of decision makers on a local, regional, national, and international scale, above all in places like the chosen one, inside an MPA. Remote sensing through the use of RPAS (Remotely Piloted Aircraft Systems or Drones) has proved to be very useful for identifying phenomena that act on a small spatial scale and in supporting and implementing protective measures according to the adaptive management approach, through multi-year surveys on habitats of conservation interest [18]. For the implementation of fine-scale monitoring actions, we have chosen products from the Sentinel satellite of the Copernicus constellation (European Space Agency - ESA). In this context, the use of satellite products provides a recurrent view of the ground, useful in the short and long-term monitoring of changes in wide coastal areas, and in particular, offers a coastline positioning evaluation in near real-time. Local monitoring actions performed in recent years have already shown an erosive trend in the past decades, and even, negative forecasts for the next decade, so further surveys with mixed methodologies could be crucial in the evaluation of the evolution of this particular coastal area by local authorities

ATLAS RPC Cosmic Ray Teststand at INFN Lecce

We describe the design and functionality of the cosmic ray teststand built at INFN Lecce for ATLAS RPC quality control assurance.Comment: XXIV Physics in Collisions Conference (PIC04), Boston, USA, June 2004, 3 pages, LaTex, 2 eps figures. MONP0

Characterization of Prototype BTeV Silicon Pixel Sensors Before and After Irradiation

We report on measurements performed on silicon pixel sensor prototypes exposed to a 200 MeV proton beam at the Indiana University Cyclotron Facility. The sensors are of n+/n/p+ type with multi-guard ring structures on the p+-side and p-stop electrode isolation on the n+-side. Electrical characterization of the devices was performed before and after irradiation up to a proton fluence of 4E14 p/cm2. We tested pixel sensors fabricated from normal and oxygen-enriched silicon wafers and with two different p-stop isolation layouts: common p-stop and individual p-stop.Comment: 8 pages in postscript format. Presented at 2001 IEEE Nuclear Science Symposium 4-10 November 2001 San Diego, Californi

Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure

Aims Left ventricular (LV) mass increase is considered part of composite target organ damage in hypertension and an independent risk factor for cardiovascular (CV) events. This study was designed to explore whether left ventricular mass index (LVMI) is associated with cognitive decline and dementia in elderly subjects, independently of blood pressure (BP) levels. Methods and results Four hundred subjects (mean age 79 ± 6 years) were studied. Left ventricular mass was measured echocardiographically in accordance with American Society of Echocardiography and normalized for body height to the 2.7 (LVMI). Global cognitive function was evaluated with the mini-mental state examination (MMSE) (maximum score 30). Dementia was defined as an MMSE score <21. Arterial stiffness was evaluated as carotid–femoral pulse wave velocity by Complior®. Prevalence of hypertension was 70% and diabetes mellitus was diagnosed in 25%. No significant differences in traditional CV risk factors were observed across LVMI quartiles. Mini-mental state examination showed an inverse trend across LVMI quartiles (the higher the LVMI, the lower the MMSE, P for trend <0.05); systolic and diastolic BP levels were not different across LVMI quartiles. In multivariable logistic regression models, including age, sex, BP levels, and use of antihypertensive drugs as covariates, the highest LVMI was found to be independently associated with a two-fold higher likelihood of having dementia. The association persisted significant even after adjustment for arterial stiffness. Conclusion In elderly subjects, LVMI is associated with a progressive cognitive decline. This association is independent of BP levels and/or large artery stiffness

Gpr investigation at the archaeological site of le cesine, lecce, italy

In this contribution, we present some results achieved in the archaeological site of Le Cesine, close to Lecce, in southern Italy. The investigations have been performed in a site close to the Adriatic Sea, only slightly explored up to now, and where the presence of an ancient Roman harbour is alleged on the basis of remains visible above all under the current sea level. This measurement campaign has been performed in the framework of a short-term scientific mission (STSM) performed in the framework of the European Cost Action 17131 (acronym SAGA), and has been aimed to identify possible points where future localized excavation might and hopefully will be performed in the next few years. Both a traditional elaboration and an innovative data processing based on a linear inverse scattering model have been performed on the data