Critical Cooperation Range to Improve Spatial Network Robustness

A robust worldwide air-transportation network (WAN) is one that minimizes the number of stranded passengers under a sequence of airport closures. Building on top of this realistic example, here we address how spatial network robustness can profit from cooperation between local actors. We swap a series of links within a certain distance, a cooperation range, while following typical constraints of spatially embedded networks. We find that the network robustness is only improved above a critical cooperation range. Such improvement can be described in the framework of a continuum transition, where the critical exponents depend on the spatial correlation of connected nodes. For the WAN we show that, except for Australia, all continental networks fall into the same universality class. Practical implications of this result are also discussed

The Swiss Board Directors Network in 2009

We study the networks formed by the directors of the most important Swiss boards and the boards themselves for the year 2009. The networks are obtained by projection from the original bipartite graph. We highlight a number of important statistical features of those networks such as degree distribution, weight distribution, and several centrality measures as well as their interrelationships. While similar statistics were already known for other board systems, and are comparable here, we have extended the study with a careful investigation of director and board centrality, a k-core analysis, and a simulation of the speed of information propagation and its relationships with the topological aspects of the network such as clustering and link weight and betweenness. The overall picture that emerges is one in which the topological structure of the Swiss board and director networks has evolved in such a way that special actors and links between actors play a fundamental role in the flow of information among distant parts of the network. This is shown in particular by the centrality measures and by the simulation of a simple epidemic process on the directors network.Comment: Submitted to The European Physical Journal

Expression profiling of microRNAs and isomiRs in conventional central chondrosarcoma

Conventional central chondrosarcoma (CCC) is a malignant bone tumor that is characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effects on CCC, treatment of most patients depends on surgical resection. This study aimed to identify the expression profiles of microRNAs (miRNAs) and isomiRs in CCC tissues to highlight their possible participation to the regulation of pathways critical for the formation and growth of this type of tumor. Our study analyzed miRNAs and isomiRs from Grade I (GI), Grade II (GII), and Grade III (GIII) histologically validated CCC tissue samples. While the different histological grades shared a similar expression profile for the top abundant miRNAs, we found several microRNAs and isomiRs showing a strong different modulation in GII + GIII vs GI grade samples and their involvement in tumor biology could be consistently hypothesized. We then in silico validated these differently expressed miRNAs in a larger chondrosarcoma public dataset and confirmed the expression trend for 17 out of 34 miRNAs. Our results clearly suggests that the contribution of miRNA deregulation, and their targeted pathways, to the progression of CCC could be relevant and strongly indicates that when studying miRNA deregulation in tumors, not only the canonical miRNAs, but the whole set of corresponding isomiRs should be taken in account. Improving understanding of the precise roles of miRNAs and isomiRs over the course of central chondrosarcoma progression could help identifying possible targets for precision medicine therapeutic intervention

Production of 5-hydroxy-7-methoxy-4-methylphthalide in a culture of Penicillium crustosum.

The chemical reactions carried out by microorganisms have been used as a tool in modern chemistry. This paper reports the production of mycophenolic acid and a new phthalide by the endophytic fungus Penicillium crustosum obtained from coffee seeds. The fungus was cultivated in a liquid medium for a period of seven days and after that the culture medium was divided into four treatments: A, B, C and D, to which different organic substances were added. Treatment A was maintained as the control to evaluate the occurrence of biotransformation. Organic acids were added to the culture media of treatments B (ferulic and quinic acids) and C [cinnamic and 3,4-(methylenedioxy) cinnamic acids], and caffeine was added in the treatment D. All these organic compounds were dissolved in DMSO, and the fermentation was maintained for more 13 days, totalizing 20 days. Mycophenolic acid was isolated from the culture with no added acids (treatment A). Mycophenolic acid and a new phthalide, 5-hydroxy-7-methoxy-4-methylphthalide were isolated from treatments B and C, and mycophenolic acid and caffeine (added to the culture medium) were isolated from treatment D. The structures were determined by NMR techniques and confi rmed by MS and MS/MS technique

The “Personal Health Budget” intervention model in early psychosis: Preliminary findings from the Parma experience

Objectives Personal Health Budget (PHB) has recently been provided to people with severe mental illness, reflecting a policy shift towards a personalized mental health care based on individual unmet needs. However, evidence on effectiveness of PHB initiatives is still limited. Aim of this research was to provide preliminary data about the beneficial effects of adding PHB to a multicomponent EIP intervention in patients with First-Episode Psychosis (FEP) along a 2-year follow-up period. Methods Participants (n = 49) were FEP patients, aged 18-50 years, entered the “Parma Early Psychosis” program and completing the Health of Nation Outcome Scale (HoNOS), the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF). Friedman test for repeated measure (with Wilcoxon test as post-hoc procedure) was performed to evaluate the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also carried out. Results A significant effect of time on all HoNOS, BPRS and GAF scores along the 2 years of follow-up was found. Regression analysis results specifically showed a relevant association between a PHB multiaxial intervention and the longitudinal decrease in BPRS “Negative Symptoms” subscores, as well as in HoNOS “Behavioral Problems” and “Social Problems” scores. Conclusions Our results support the general applicability of a PHB approach within an “Early Intervention in Psychosis” program for help-seeking adults with FEP

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations.

Abstract BACKGROUND: We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data. METHODS: We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). RESULTS: The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. CONCLUSIONS: PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied

Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients

ABSTRACT: BACKGROUND: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. METHODS: Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. RESULTS: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. CONCLUSIONS: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management

Local Optima Networks of the Permutation Flow-Shop Problem

International audienceThis article extracts and analyzes local optima networks for the permutation flow-shop problem. Two widely used move operators for permutation representations, namely, swap and insertion, are incorporated into the network landscape model. The performance of a heuristic search algorithm on this problem is also analyzed. In particular, we study the correlation between local optima network features and the performance of an iterated local search heuristic. Our analysis reveals that network features can explain and predict problem difficulty. The evidence confirms the superiority of the insertion operator for this problem

4,4′-Dipyridyl Dioxide·SbF3 Cocrystal: Pnictogen Bond Prevails over Halogen and Hydrogen Bonds in Driving Self-Assembly

The SbF3·4,4′-dipyridyl N,N′-dioxide cocrystal is prepared and characterized via infrared spectroscopy and 121Sb and 123Sb nuclear quadrupole resonance. Single crystal X-ray analysis proves that a major role in cocrystal formation is played by Sb···O pnictogen bonds, the attractive interactions wherein antimony and oxygen act as the electrophilic and nucleophilic sites, respectively. Molecular electrostatic potential and natural bond orbital analyses confirm the relevance of this interaction in the self-assembly process. Dipyridyl dioxide also forms hydrogen bonded and halogen bonded cocrystal, e.g., when water and 1,4-diiodo-tetrafluoro-benzene function as acceptors of electron density. Experiments of competitive cocrystal formation indicate that under the adopted conditions the pnictogen bond prevails over the halogen bond and the hydrogen bond in identifying the tecton involved in cocrystal formation with dipyridyl dioxide