An approximation algorithm for the maximum cut problem and its experimental analysis

AbstractAn approximation algorithm for the maximum cut problem is designed and analyzed; its performance is experimentally compared with that of a neural algorithm and that of Goemans and Williamson's algorithm. Although the guaranteed quality of our algorithm in the worst-case analysis is poor, we give experimental evidence that its average behavior is better than that of Goemans and Williamson's algorithm

Human herpesvirus 6: An emerging pathogen.

Infections with human herpesvirus 6 (HHV-6), a beta-herpesvirus of which two variant groups (A and B) are recognized, is very common, approaching 100% in seroprevalence. Primary infection with HHV-6B causes roseola infantum or exanthem subitum, a common childhood disease that resolves spontaneously. After primary infection, the virus replicates in the salivary glands and is shed in saliva, the recognized route of transmission for variant B strains; it remains latent in lymphocytes and monocytes and persists at low levels in cells and tissues. Not usually associated with disease in the immunocompetent, HHV-6 infection is a major cause of opportunistic viral infections in the immunosuppressed, typically AIDS patients and transplant recipients, in whom HHV-6 infection/reactivation may culminate in rejection of transplanted organs and death. Other opportunistic viruses, human cytomegalovirus and HHV-7, also infect or reactivate in persons at risk. Another disease whose pathogenesis may be correlated with HHV-6 is multiple sclerosis. Data in favor of and against the correlation are discussed

Precise eye localization through a general-to-specific model definition

We present a method for precise eye localization that uses two Support Vector Machines trained on properly selected Haar wavelet coefficients. The evaluation of our technique on many standard databases exhibits very good performance. Furthermore, we study the strong correlation between the eye localization error and the face recognition rate

Lung nodules detection and classification

Image processing techniques and Computer Aided Diagnosis (CAD) systems have proved to be effective for the improvement of radiologists' diagnosis. In this paper an automatic system detecting lung nodules from Postero Anterior Chest Radiographs is presented. The system extracts a set of candidate regions by applying to the radiograph three different and consecutive multi-scale schemes. The comparison of the results obtained with those presented in the literature show the efficacy of our multi-scale framework. Learning systems using as input different sets of features have been experimented for candidates classification, showing that Support Vector Machines (SVMs) can be successfully applied for this task

Immunotherapeutic efficacy of retargeted ohsvs designed for propagation in an ad hoc cell line

Our laboratory has pursued the generation of cancer‐specific oncolytic herpes simplex viruses (oHSVs) which ensure high efficacy while maintaining a high safety profile. Their blueprint included retargeting to a Tumor‐Associated Antigen, e.g., HER2, coupled to detargeting from natural receptors to avoid off‐target and off‐tumor infections and preservation of the full complement of unmodified viral genes. These oHSVs are “fully virulent in their target cancer cells”. The 3rd generation retargeted oHSVs carry two distinct retargeting moieties, which enable infection of a producer cell line and of the target cancer cells, respectively. They can be propagated in an ad hoc Vero cell derivative at about tenfold higher yields than 1st generation recombinants, and more effectively replicate in human cancer cell lines. The R‐335 and R‐337 prototypes were armed with murine IL‐12. Intratumorally‐administered R‐337 conferred almost complete protection from LLC‐ 1‐HER2 primary tumors, unleashed the tumor microenvironment immunosuppression, synergized with the checkpoint blockade and conferred long‐term vaccination against distant challenge tumors. In summary, the problem intrinsic to the propagation of retargeted oHSVs—which strictly require cells positive for targeted receptors—was solved in 3rd generation viruses. They are effective as immunotherapeutic agents against primary tumors and as antigen‐agnostic vaccines

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely

Automatic Segmentation of Mouse Images

Genetic engineering has enabled the generation of organisms where molecular reactions in response to patho-physiological events can be measured in real-time by means of molecular imaging. This novel technology with the generation of reporter cell systems, that is cells engineered to express a bioluminescent protein in response to selected stimuli, had a major impact in pharmacological research. The recent generation of reporter mice, where the activity of a specific drug can be studied systematically, hold the promise to strengthen preclinical studies, providing a very rapid and comprehensive view on drug pharmacokinetics and activity in whole organisms. To date, a major limitation to the use of in vivo imaging for pharmaco-toxicological purposes resides in the limited throughput of the methodology: even if up to 100 animals can be reasonably processed in a day by some imaging techniques, the analysis of the data, including the identification and quantification of signals belonging to different mouse body areas, requires time and trained personnel, to manually identify specific body areas where drug effects can be measured. For this reason, we have developed an algorithm to automatically identify (segment) the body areas of a given reporter mouse. Automatic segmentation is obtained by combining classical image processing and pattern recognition techniques. The algorithm has been tested on more than 1000 mouse images differing for sex, pose and lighting conditions, and acquired by devices of different companies. Our algorithm, not only increases processivity (the whole dataset analyzed by a trained scientist in a week was processed overnight by our software), but also provides more accurate results. In conclusion, automatic systems may outperform current manual image analysis, allowing to obtain a detailed comprehension of real-time molecular processes in living animals with a standardized, rapid, and cost-effective approach. This work was supported by EC. (STREP EWA LSHM-CT-2005-518245) NIH (RO1AG027713) to A.M

Safety and clinical outcomes of abiraterone acetate (aa) after docetaxel (doc) in octogenarians with metastatic castration-resistant prostate cancer (mcrpc)

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oHSV Genome Editing by Means of galK Recombineering

open8noThis work was supported by European Research Council (ERC) Advanced Grant number 340060, VII framework program to G. C.-F., by RFO (University of Bologna) to L.M. and T.G, and by Fondi Pallotti to T.G.Since the cloning of the herpes simplex virus (HSV) genome as BAC (bacterial artificial chromosome), the genetic engineering of the viral genome has become readily feasible. The advantage is that the modification of the animal virus genome is carried out in bacteria, with no replication or production of viral progeny, and is separated from the reconstitution or regeneration of the recombinant virus in mammalian cells. This allows an easy engineering of essential genes, as well. Many technologies have been developed for herpesvirus BAC engineering. In our hands the most powerful is galK recombineering that exploits a single marker (galK) for positive and negative selection and PCR amplicons for seamless modification in the desired genome locus. Here we describe the engineering of the HSV recombinant BAC 115 by the insertion of a heterologous cassette for the expression of murine interleukin 12 (mIL12) in the intergenic sequence between US1 and US2 ORFs.embargoed_20201017Laura Menotti, Valerio Leoni, Valentina Gatta, Biljana Petrovic, Andrea Vannini, Simona Pepe, Tatiana Gianni, Gabriella Campadelli-FiumeLaura Menotti, Valerio Leoni, Valentina Gatta, Biljana Petrovic, Andrea Vannini, Simona Pepe, Tatiana Gianni, Gabriella Campadelli-Fium