Bulk detection of time-dependent topological transitions in quenched chiral models

The topology of one-dimensional chiral systems is captured by the winding number of the Hamiltonian eigenstates. Here we show that this invariant can be read-out by measuring the mean chiral displacement of a single-particle wavefunction that is connected to a fully localized one via a unitary and translational-invariant map. Remarkably, this implies that the mean chiral displacement can detect the winding number even when the underlying Hamiltonian is quenched between different topological phases. We confirm experimentally these results in a quantum walk of structured light

A convenient preparation of La2CuO4 from molecular precursors

Exhaustive hydrolysis of a mixture of [La4(CO3)(O2CNBu2)10] and [Cu(O2CNBu2)(py∗)2] (py∗ = 4-dimethylamino pyridine) in molar ratio 1/2 corresponding to a La/Cu molar ratio 2/1 was carried out in toluene at room temperature. The carbamato derivatives of lanthanum and copper can be easily prepared by extraction of the metal ions from aqueous solution into heptane by the NHBu2/CO2 system, according to a method previously reported. The copper precursor was selected among a number of derivatives in respect of its easy tractability. The tetragonal modification T’ of La2CuO4 was obtained by treatment at 600 °C of the intermediate mixed carbonate. The thermal treatment of T’-La2CuO4 at 850 °C, followed by cooling down to room temperature, afforded the orthorhombic modification of the mixed oxide

Distilling the topology of the Hofstadter model through a diffraction experiment

In two and three spatial dimensions, the transverse response experienced by a charged particle on a lattice in a uniform magnetic field is proportional to a topological invariant, the first Chern number, characterizing the energy bands of the underlying Hofstadter Hamiltonian. In four dimensions, the transverse response is also quantized, and controlled by the second Chern number. These remarkable features solely arise from the magnetic translational symmetry. Here we show that the symmetries of the two-, three- and four-dimensional Hofstadter Hamiltonians may be encrypted in optical diffraction gratings, such that simple photonic experiments allow one to extract the first and the second Chern numbers of the whole energy spectra. This result is particularly remarkable in three and four dimensions, where complete topological characterizations have not yet been achieved experimentally. Side-by-side to the theoretical analysis, in this work we present the experimental study of optical gratings analogues of the two- and three-dimensional Hofstadter models

Minorenni vittime di omicidio a Milano (Italia): 1993-2017

This study aims to examine the phenomenon of homicide with victims under 18 years-old in a wide and multiethnic metropolitanarea in the north of Italy. We’re dealing with a type of crime that generates a widespread alarm and a common concern.The data analysis, approached with a multidisciplinary strategy, presented in this paper is based on forensic reports of the Instituteof Legal Medicine of the University of Milan, to provide a detailed framework of the homicides of minors that took place inthe territorial jurisdiction of Milan and Monza Prosecutor’s Office between 1993 and 2017. Quantitative and qualitative analysiswere conducted regarding victims’ socio-demographic characteristics (gender, age, nationality), weapons used, places and modalityof body discovery, murderers, motives of the killing and type of relationship between offenders and victims. Purpose of thispaper is to compare the present set of data with the ones provided by the international literature, as well as make some criminologicalobservations on this matter with a view to preventing the phenomenon. To this end, some representative case studieshave been added, their characteristics and also the relationships between offender and victim have been discussed.Questo studio esamina il fenomeno dell'omicidio con vittime di età inferiore ai 18 anni in una vasta e multietnica area metropolitanadel nord Italia, un tipo di crimine che genera allarme e preoccupazione. L'analisi dei dati, affrontata con una metodologia multidisciplinare,è basata sui verbali autoptici dell'Istituto di Medicina Legale dell'Università di Milano, al fine di fornire un quadro dettagliatodegli omicidi con vittima minorenne che si sono verificati nella giurisdizione territoriale della Procura di Milano e Monzatra il 1993 e il 2017. Sono state condotte analisi quantitative e qualitative sulle vittime, quali le caratteristiche socio-demografiche(genere, età, nazionalità), le armi utilizzate, i luoghi e le modalità di rinvenimento del corpo, le caratteristiche dell’omicida, i motividell'uccisione e il tipo di relazione tra criminale e vittima. Scopo di questo studio è confrontare l'attuale insieme di dati con quelliforniti dalla letteratura internazionale, nonché porre alcune considerazioni di carattere preventivo. A tal fine, sono stati presentatianche alcuni casi studio rappresentativi, discutendone le caratteristiche peculiari e le relazioni tra l'autore del reato e la vittima

Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.

Selective degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is initiated by ER-phagy receptors, which facilitate the incorporation of ER fragments into autophagosomes. FAM134 reticulon family proteins (FAM134A, FAM134B, and FAM134C) are ER-phagy receptors with structural similarities and nonredundant functions. Whether they respond differentially to the stimulation of ER-phagy is unknown. Here, we describe an activation mechanism unique to FAM134C during starvation. In fed conditions, FAM134C is phosphorylated by casein kinase 2 (CK2) at critical residues flanking the LIR domain. Phosphorylation of these residues negatively affects binding affinity to the autophagy proteins LC3. During starvation, mTORC1 inhibition limits FAM134C phosphorylation by CK2, hence promoting receptor activation and ER-phagy. Using a novel tool to study ER-phagy in vivo and FAM134C knockout mice, we demonstrated the physiological relevance of FAM134C phosphorylation during starvation-induced ER-phagy in liver lipid metabolism. These data provide a mechanistic insight into ER-phagy regulation and an example of autophagy selectivity during starvation.We thank G. Diez Roux and P. Ashley-Norman for critical reading of the manuscript. We thank the microscopy, MS, advanced histopathology, and FACS facilities at TIGEM Institute. We thank E. Nusco for helping us with AAV injections. Funding: This work was supported by European Research Council (ERC) (714551), Telethon intramural grants, and Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2015 Id 17717) (to C.S.) and Telethon Foundation (TMPGCBX16TT), AFM Telethon (Trampoline Grant), and AIRC (MFAG-2020-24856) (to P.G.). G.D.L. is a recipient of AIRC fellowship “Francesco Alicino” (25407). V.L. acknowledges funding from the ERC (101001784), the Italian MIUR-PRIN 2017 (2017FJZZRC), and the Swiss National Supercomputing Center (CSCS) (project ID u8). The work of A.S. was supported by the German Research Foundation DFG (SFB1177/2 and WO210/20-2) and the Dr. Rolf M. Schwiete Stiftung (13/2017). A.E. is supported by the RETOS projects Programme of Spanish Ministry of Science, Innovation and Universities, Spanish State Research Agency (grants SAF2015-67538-R and PID2019-104012RB-I00), and the ERC (638891). A.B.P.-G. is a recipient of Ph.D. fellowship from MICIU/AEI (BES-2017-081381). A.R. is a recipient of Umberto Veronesi Foundation postdoctoral fellowship. Author contributions: G.D.L. and F.I. performed most of the experiments. F.I. and A.B.P.-G. performed in vivo experiments. M.M. performed mutagenesis experiments. S.A. and V.L. performed LC3-FAM134C binding analysis. C.P.Q.M. performed in vitro phosphorylation assays. L.C. analyzed CK2 substrate phosphorylation. F.S., A.P., C.C., and A.S. analyzed proteomic data. G.N. provided critical suggestions. A.R. performed proteomic experiments. A.E. supervised in vivo experiments. M.R., L.A.P., and O.M. supervised CK2 experiments. C.S. designed the study. P.G. and C.S. conceived and supervised the experiments. C.S., P.G., V.L., and M.R. wrote the paper. G.D.L. and F.I. prepared the figures. All the authors read the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.S

Radiotherapy at oligoprogression for metastatic castration-resistant prostate cancer patients: a multi-institutional analysis

Purpose To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). Materials and methods mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan-Meier method; univariate and multivariate analyses were performed. Results Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1-44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade >= 2 toxicity. Conclusion Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed

The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures

: Non-small cell lung cancer (NSCLC) represents the perfect paradigm of 'precision medicine' due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of 'oncogene addicted' NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC

I.S.Mu.L.T. Achilles Tendon Ruptures Guidelines

This work provides easily accessible guidelines for the diagnosis, treatment and rehabilitation of Achilles tendon ruptures. These guidelines could be considered as recommendations for good clinical practice developed through a process of systematic review of the literature and expert opinion, to improve the quality of care for the individual patient and rationalize the use of resources. This work is divided into two sessions: 1) questions about hot topics; 2) answers to the questions following Evidence Based Medicine principles. Despite the frequency of the pathology andthe high level of satisfaction achieved in treatment of Achilles tendon ruptures, a global consensus is lacking. In fact, there is not a uniform treatment and rehabilitation protocol used for Achilles tendon ruptures