INGV strong-motion data web-portal: a focus on the Emilia seismic sequence of May-June 2012

In Italy, strong-motion monitoring was started in 1972 by different Institutions, although mainly through Ente Nazionale per l'Energia Elettrica (ENEL; Italian National Electricity Company) and Dipartimento della Protezione Civile (DPC; Italian Department of Civil Protection), with different purposes. These included permanent acceleromet- ric monitoring and temporary monitoring during seismic se- quences or before permanent installation. Today, the National Accelerometric Network (RAN; Rete Accelero- metrica Nazionale) [Gorini et al. 2010, Zambonelli et al. 2011] is operated by the DPC and consists of 464 digital sta- tions. These are distributed throughout the whole national territory, with a prevalence for areas of major seismicity. In 2006, the INGV began strong-motion monitoring, by installing 22 accelerometric stations in northern Italy (RAIS; Rete Accelerometrica Italia Settentrionale; Accelerometric Network of Northern Italy; http://rais.mi.ingv.it/). In 2008, the monitoring was extended to a national scale: this effort led to the installation of 105 accelerometers, collocated with the velocimetric sensors, in selected Rete Sismica Nazionale (RSN; National Seismic Network) sites [Amato and Mele 2008] that are managed by the Centro Nazionale Terremoti (CNT; National Earthquake Centre). Overall, the 127 strong- motion stations that form the INGV Italian strong-motion network homogeneously cover the whole Italian territory. The progress achieved in Italy in the field of strong-mo- tion monitoring and strong-motion data archiving and dis- semination was illustrated in a recently published special issue of the Bulletin of Earthquake Engineering [Luzi et al. 2010]. The strong-motion data recorded by the RAN have been distributed and are available on request to the DPC and to the Italian Accelerometric Archive (ITACA), as the Italian strong-motion database (http://itaca.mi.ingv.it/) [Pacor et al. 2011a], which has been updated with records to 2009. The INGV strong-motion data are archived in real-time and dis- tributed through the European Integrated Data Archive (EIDA; http://eida.rm.ingv.it/) web portal. Recently, an INGV working group developed the first version of a web portal with the aim of archiving, processing and distributing accelerometric data recorded by permanent and temporary INGV stations. This web portal (www.mi. ingv.it/ISMD/; Figure 1, top panel) is composed of two main modules: the former is known as the INGV Strong Motion Data (ISMD, www.mi.ingv.it/ISMD/ismd.h tml/; Figure 1, bottom left panel) and has as its main scope the analyse and distribution in quasi-real time (a few hours after event oc- currence) of the uncorrected accelerometric data, and the related metadata obtained after an automatic processing pro- cedure. This latter, known as the Dynamic Archive (DYNA, http://dyna.mi.ingv.it/DYNA-archive/; Figure 1, bottom right panel) is a dynamic database where manually post- processed accelerometric waveforms are provided, together with their metadata. Both of these archives are designed and structured in such a way that their compilations and updat- ing will be almost completely automatic. At the end of May 2012, a first prototype of the ISMD module was published, providing the uncorrected strong- motion data recorded by the INGV stations for the main events of the Emilia seismic sequence [Massa et al. 2012]

Functionalized silica nanoparticles in the detection and treatment of Her2-positive breast cancer

Introduction: Nanobiotechnology can provide the development of nanoparticles for diagnosis/treatment of human cancer. Aim of this work was to validate a silica nanoparticles (SNP)-based system functionalized with anti-Her2 antibody fragment and loaded with radioactive/fluorescent probes for detection of aggressive breast cancer. Methods: SNPs carrying (ETZ-2) or not (ETZ-1, control) the Her2 antibody fragment were used in in vitro binding kinetic in Her2 positive (SKBR-3) and negative (MDA-MB-468) breast cancer cell lines. In parallel, the same SNPs were derivatized with nitril-triacetic acid and reacted with His-Tag, previously labelled with 99mTc-Tricarbonyl complex. Labelled SNPs were used for different experiments: in vitro uptake kinetic in SKBR-3 and MDA-MB-468 cells (20 min, 1 h, 4h and 24h); ex vivo distribution in tumour and peripheral organs in animals implanted with MDA-MB-468 or SKBR-3 cells, at 4h from ETZ-2 injection. SNPs binding in cells was expressed as percentage of the total radioactivity counted; uptake in tumours and tissues were calculated as percentage of injected dose per gram of tissue. Slices of tumour were also fixed with 4% PAF and observed by fluorescence. In parallel, additional animals bearing SKBR-3 or MDA-MB-468 lesions were treated with liposomal doxorubicin (3 mg/kg in 40\ub5l) or vehicle, and tumour uptake of [18F]FDG and [11C]Choline was evaluated ex vivo with double autoradiography. Results: ETZ-2 specifically binds SKBR-3 cells in vitro, reaching a maximum uptake ratio of 2,1 on MDA-MB-468 cells after 4h. The same result was confirmed in tumours, after the biodistribution study and observation in fluorescence. Standard treatment particularly affected SKBR-3 lesions growth, in which we observed a 12,4% decrease of [18F]FDG and a 14.3% increase of [11C]Choline uptake, compared to control. Comparison with NPSs filled with doxorubicin are in progress. Conclusion: Labelled SNPs resulted a useful detection system for Her2 positive breast cancer and could be used for targeted therapy

Functionalized silica nanoparticles in the detection and treatment of Her2-positive breast cancer

Introduction: Nanobiotechnology can provide the development of nanoparticles for diagnosis/treatment of human cancer. Aim of this work was to validate a silica nanoparticles (SNP)-based system functionalized with anti-Her2 antibody fragment and loaded with radioactive/fluorescent probes for detection of aggressive breast cancer. Methods: SNPs carrying (ETZ-2) or not (ETZ-1, control) the Her2 antibody fragment were used in in vitro binding kinetic in Her2 positive (SKBR-3) and negative (MDA-MB-468) breast cancer cell lines. In parallel, the same SNPs were derivatized with nitril-triacetic acid and reacted with His-Tag, previously labelled with 99mTc-Tricarbonyl complex. Labelled SNPs were used for different experiments: in vitro uptake kinetic in SKBR-3 and MDA-MB-468 cells (20 min, 1h, 4h and 24h); ex vivo distribution in tumour and peripheral organs in animals implanted with MDA-MB-468 or SKBR-3 cells, at 4h from ETZ-2 injection. Afterwards, an additional experiment with ex vivo distribution and autoradiography at different time points (4h, 6h and 24h; n=4) were performed after the injection of labelled ETZ-1 and 2 SNPS on animals implanted with SKBR-3 cells. At the same times, in vitro uptake of both SNPs were measured by pre-treating SKBR-3 cells with 1 mg/ml of Trastuzumab. The uptake of labelled SNPs in cells was expressed as percentage of the total radioactivity counted, while in tumours and tissues was calculated as percentage of injected dose per gram of tissue (%ID/g). Tumour sample were also frozen in liquid N2 and sectioned for fluorescence microscopy. We have ongoing the evaluation of doxorubicin filled SNPs in comparison to liposomal doxorubicin (Caelix, 3 mg/kg in 40\ub5l) to assess the efficacy of nanoparticles to targeting chemotherapy. The effect will be assessed by measuring tumoral features as volume and [18F]FDG and [11C]Choline uptake. Results: ETZ-2 specifically binds SKBR-3 cells in vitro, reaching a maximum uptake ratio of 2,1 on MDA-MB-468 cells after 4h. The same result was confirmed in tumours, after the biodistribution study and observation in fluorescence. Caelix treatment particularly affected SKBR-3 lesions growth, in which we observed a 12,4% decrease of [18F]FDG and a 14.3% increase of [11C]Choline uptake, compared to control. Comparison with filled doxorubicin NPSs are in progress. Conclusion: Preliminary results showed that 99mTc-ETZ-2 SNPs could be a useful system for Her2 positive breast cancer detection and treatment

The May 2012 Pianura Padano-Emiliana seismic sequence: INGV strong-motion data website

On May 20th 2012, 06:03:02 UTC, a ML 5.9 (Mw 6.0) earthquake struck the Northern Italy (http://cnt.rm.ingv.it/tdmt.html). The epicenter was localized at 11.23° E and 44.89° N, in an area among the cities of Ferrara, Modena and Mantova. The event occurred at a depth of about 6.30 km, and was characterized by a reverse focal mechanism (http://cnt.rm.ingv.it/). From May 20th, thousand of earthquakes, the strongest of which with a ML 5.8 (May 29th, 07:00:03 UTC), occurred in the same area (http://iside.rm.ingv.it/). This note presents a new web site, www.mi.ingv.it/ISMD/ that includes about 2.000 threecomponents strong-motion recordings related to the events with 4.0 ≤ ML ≤ 5.9 occurred in the central part of the Pianura Padano-Emiliana (Northern Italy) from May 20th to June 3rd. The data come from all INGV strong-motion stations installed in Northern Italy (i.e. Strong-Motion Network of Northern Italy, RAIS, http://rais.mi.ingv.it/, Augliera et al., 2011; strong-motion stations of the National Seismic Network, RSN, http://cnt.rm.ingv.it) and selected with a minimum latitude of 43.5°N. The earthquake locations reported in the web site come from the National Earthquake Center of INGV (preliminary location form: http://cnt.rm.ingv.it/). An automatic procedure was developed in order to publish in the web site both metadata (processed by an automatic system) and downloadable waveforms in ascii format (uncorrected version). After each earthquake occurrence, the procedure downloads 5 minutes (starting from the event origin time) of MINI-Seed waveforms from EIDA (http://eida.rm.ingv.it/) archive and applies a fast processing and data analysis tool. The automatic data processing includes: i) a first-order baseline operator applied to the entire record, in order to have a zero-mean of the signal; ii) a baseline correction, in order to remove the linear trend, computed with a least square method; iii) tapering of the signal through a cosine function (0.01%) at the beginning and at the end of each selected window; iv) the application of a 4th order Butterworth band-pass acausal (Boore and Akkar, 2003; Boore and Bommer, 2005) filter in order to remove the high and low-frequency noise: the filter cut-off thresholds were automatically selected on the basis of the event magnitude (i.e., 0.1-40 Hz with ML ≥ 5.5; 0.2-35 Hz with 4.5 ≤ ML < 5.5; 0.3-35 with 3.5 ≤ ML < 4.5). Considering the available digital instrumentation (i.e. 24 bits Kinemetrics Episensor with a flat response up to 200 Hz) the deconvolution for the instrument response was not applied. At the end velocity waveforms were obtained through integration of the processed accelerometric data. For each component of the automatically processed signals the following GM parameters are evaluated: PGA (peak ground acceleration), PGV (peak ground velocity) and SA (5%-damped acceleration response spectra) for periods up to 4 s were calculated. Moreover, the automatic system provides PSV (5%-damped pseudo-velocity response spectra), Sd (5%-damped displacement response spectra), Ia (Arias Intensity; Arias 1970) and Ih (Housner intensity; Housner 1952). In correspondence of each recording site the horizontal-to-vertical spectral ratio (HVSR) was automatically performed considering 5 s and 10 s of S phase (starting from 1s before the S-phase onset). At the end of the automatic procedure, for each single event, a web page is generated. On each web page the results are published in terms of tables (text format) containing main strong-motion parameters and generic plots (e.g., location of recording stations, HVSRs, response spectra, accelerograms, comparison between recorded data and Italian Ground Motion Prediction Equations, Bindi et al., 2011). For each event the strong-motion records, in uncorrected ascii-format, are downloadable. Following the standards of the ITalian ACcelerometric Archive, ITACA (http://itaca.mi.ingv.it, Pacor et al., 2011), the waveforms ascii files are composed of 43 header lines followed by acceleration data in cm/s2

Mengukur Kesehatan dan Perkembangan Koperasi dengan Model Analisis Keuangan (Studi Kasus Koperasi Simpan Pinjam Pegawai Negri Kota Magelang Periode 2012-2016)

Penelitian ini bertujuan untuk mengetahui Kesehatan Koperasi melalui kinerja keuangan Koperasi di Kota Magelang ditinjau dari aspek likuiditas, solvabilitas, dan rentabilitas sebagai dasar untuk menetapkan kebijakan bagi pihak manajemen dalam pengambilan keputusan dalam beberapa tahun berjalan pada tahun 2012, 2013, 2014, 2015 dan 2016. Rumusan masalah dari penelitian ini adalah “Apakah kinerja keuangan Koperasi di Kota Magelang semakin baik di tinjau dari rasio likuiditas, solvabilitas, dan rentabilitas pada tahun 2016 dibandingkan dengan tahun 2015, 2014, 2013 dan 2012”. Alat analisis yang digunakan dalam penelitian ini adalah analisis rasio keuangan yaitu : rasio likuditas, rasio solvabilitas, dan rasio rentabilitas untuk menganalisis bahwa kinerja keuangan mengalami perkembangan dari tahun ke tahun periode 2012 – 2016. Hasil dari penelitian ini sebanyak sembilan koperasi dinyatakan tidak sehat dilihat dari rasio likuiditas, rasio profitabilitas dan rasio solvabilitas pada tahun 2012 – 2016

Development of 99mTc-radiolabeled nanosilica for targeted detection of HER2-positive breast cancer

Paolo Rainone,1,2,* Benedetta Riva,3,* Sara Belloli,1 Francesco Sudati,4 Marilena Ripamonti,1 Paolo Verderio,3 Miriam Colombo,3 Barbara Colzani,3 Maria Carla Gilardi,1 Rosa Maria Moresco,5 Davide Prosperi3 1Institute of Molecular Bioimaging and Physiology, CNR, Segrate (MI), 2Doctorate School of Molecular and Translational Medicine, University of Milan, Milan, 3NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Universit&agrave; di Milano-Bicocca, Milano, 4PET and Nuclear Medicine Unit, San Raffaele Scientific Institute, Milan, 5Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy *These authors contributed equally to this work Abstract: The human epidermal growth factor receptor 2 (HER2) is normally associated with a highly aggressive and infiltrating phenotype in breast cancer lesions with propensity to spread into metastases. In clinic, the detection of HER2 in primary tumors and in their metastases is currently based on invasive methods. Recently, nuclear molecular imaging techniques, including positron emission tomography and single photon emission computed tomography (SPECT), allowed the detection of HER2 lesions in vivo. We have developed a 99mTc-radiolabeled nanosilica system, functionalized with a trastuzumab half-chain, able to act as drug carrier and SPECT radiotracer for the identification of HER2-positive breast cancer cells. To this aim, nanoparticles functionalized or not with trastuzumab half-chain, were radiolabeled using the 99mTc-tricarbonyl approach and evaluated in HER2 positive and negative breast cancer models. Cell uptake experiments, combined with flow cytometry and fluorescence imaging, suggested that active targeting provides higher efficiency and selectivity in tumor detection compared to passive diffusion, indicating that our radiolabeling strategy did not affect the nanoconjugate binding efficiency. Ex vivo biodistribution of 99mTc-nanosilica in a SK-BR-3 (HER2+) tumor xenograft at 4 h postinjection was higher in targeted compared to nontargeted nanosilica, confirming the in vitro data. In addition, viability and toxicity tests provided evidence on nanoparticle safety in cell cultures. Our results encourage further assessment of silica 99mTc-nanoconjugates to validate a safe and versatile nanoreporter system for both diagnosis and treatment of aggressive breast cancer. Keywords: SPECT, targeted radionuclide imaging, silica nanoparticles, TZ-half chain conjugation, 99mTc-tricarbonyl radiolabelin