The Irreducible Spine(s) of Undirected Networks

Using closure concepts, we show that within every undirected network, or graph, there is a unique irreducible subgraph which we call its "spine". The chordless cycles which comprise this irreducible core effectively characterize the connectivity structure of the network as a whole. In particular, it is shown that the center of the network, whether defined by distance or betweenness centrality, is effectively contained in this spine. By counting the number of cycles of length 3 <= k <= max_length, we can also create a kind of signature that can be used to identify the network. Performance is analyzed, and the concepts we develop are illurstrated by means of a relatively small running sample network of about 400 nodes.Comment: Submitted to WISE 201

Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss.

Alterations of the Retinoblastoma (Rb) pathway are frequent in ovarian cancer, typically resulting from CDKN2A down-regulation, CCNE1 amplification, CCND1/2 amplification, and RB1 loss. However, bi-allelic CDKN2A mutation or homozygous deletion is a very rare event, concerning less than 5% of patients.Initial trials with palbociclib in serous ovarian cancer have shown very modest benefit in unselected patient populations, thus underlining the need for a biomarker predicting response. We report the case of a heavily pre-treated patient with a serous ovarian tumor harboring a homozygous deletion of the CDKN2A gene that derived significant, prolonged clinical benefit from palbociclib, a CDK4/6 oral inhibitor, with letrozole. Treatment with palbociclib and letrozole started on February 2018, with an ongoing response after 12 months.In conclusion, homozygous CDKN2A deletion is rare and could be used to predict response to CDK4/6 inhibitors in association with other genomic features. We encourage further trials in this direction

Targeting OLFML3 in colorectal cancer suppresses tumor growth and angiogenesis, and increases the efficacy of anti-PD1 based immunotherapy

The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC. </p

Transverse Beam Spin Asymmetries in Forward-Angle Elastic Electron-Proton Scattering

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely-polarized 3 GeV electrons from unpolarized protons at Q^2 = 0.15, 0.25 (GeV/c)^2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state, and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A_n provides a direct probe of the imaginary component of the 2-gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.Comment: 5 pages, 3 figures, submitted to Physical Review Letters; shortened to meet PRL length limit, clarified some text after referee's comment

Strange Quark Contributions to Parity-Violating Asymmetries in the Forward G0 Electron-Proton Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < Q^2 < 1.0 GeV^2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange quark contributions to the currents of the proton. The measurements were made at JLab using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate non-zero, Q^2 dependent, strange quark contributions and provide new information beyond that obtained in previous experiments.Comment: 5 pages, 2 figure

The G0 Experiment: Apparatus for Parity-Violating Electron Scattering Measurements at Forward and Backward Angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part per million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam-monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cerenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed.Comment: Submitted to Nuclear Instruments and Method

Wind-Blown Bubbles around Evolved Stars

Most stars will experience episodes of substantial mass loss at some point in their lives. For very massive stars, mass loss dominates their evolution, although the mass loss rates are not known exactly, particularly once the star has left the main sequence. Direct observations of the stellar winds of massive stars can give information on the current mass-loss rates, while studies of the ring nebulae and HI shells that surround many Wolf-Rayet (WR) and luminous blue variable (LBV) stars provide information on the previous mass-loss history. The evolution of the most massive stars, (M > 25 solar masses), essentially follows the sequence O star to LBV or red supergiant (RSG) to WR star to supernova. For stars of mass less than 25 solar masses there is no final WR stage. During the main sequence and WR stages, the mass loss takes the form of highly supersonic stellar winds, which blow bubbles in the interstellar and circumstellar medium. In this way, the mechanical luminosity of the stellar wind is converted into kinetic energy of the swept-up ambient material, which is important for the dynamics of the interstellar medium. In this review article, analytic and numerical models are used to describe the hydrodynamics and energetics of wind-blown bubbles. A brief review of observations of bubbles is given, and the degree to which theory is supported by observations is discussed.Comment: To be published as a chapter in 'Diffuse Matter from Star Forming Regions to Active Galaxies' - A volume Honouring John Dyson. Eds. T. W. Harquist, J. M. Pittard and S. A. E. G. Falle. 22 pages, 12 figure

Sviluppo pre-clinico e clinico di inibitori della cellula staminale leucemica nelle leucemie acute

In Leukemias, recent developments have demonstrated that the Hedgehog pathway plays a key-role in the peculiar ability of self renewal of leukemia stem cells. The aim of this research activity was to investigate, through a first in man, Phase I, open label, clinical trial, the role and the impact, mainly in terms of safety profile, adverse events and pharmacokinetics, of a Sonic Hedgehog inhibitor compound on a population of heavely pretreated patients affected by AML, CML, MF, or MDS, resistant or refractory to standard chemotherapy. Thirty-five patients have been enrolled. The drug was administered orally, in 28 days cycles, without rest periods. The compound showed a good safety profile. The half life was of 17-35 hours, justifying the daily administration. Significant signs of activity, in terms of reduction of bone marrow blast cell amount were seen in most of the patients enrolled. Interestingly, correlative biological studies demonstrated that, comparing the gene expression profyiling signature of separated CD34+ cells before and after one cycle of treatment, the most variably expressed genes were involved in the Hh pathway. Moreover, we observed that many genes involved in MDR (multidrug resistance)were significantly down regulated after treatment. These data might lead to future clinical trials based on combinatory approaches, including, for instance, Hh inhibitors and conventional chemotherapy

Strange Quark Contributions to Parity-Violating Asymmetries in the Forward G0 Electron-Proton Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 ≤ Q2 ≤ 1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange quark contributions to the currents of the proton. The measurements were made at JLab using a toroidal spectrom- eter to detect the recoiling protons from a liquid hydrogen target. The results indicate non-zero, Q2 dependent, strange quark contributions and provide new information beyond that obtained in previous experiments