The Varied Role of Efflux Pumps of the MFS Family in the Interplay of Bacteria with Animal and Plant Cells

Efflux pumps represent an important and large group of transporter proteins found in all organisms. The importance of efflux pumps resides in their ability to extrude a wide range of antibiotics, resulting in the emergence of multidrug resistance in many bacteria. Besides antibiotics, multidrug efflux pumps can also extrude a large variety of compounds: Bacterial metabolites, plant-produced compounds, quorum-sensing molecules, and virulence factors. This versatility makes efflux pumps relevant players in interactions not only with other bacteria, but also with plant or animal cells. The multidrug efflux pumps belonging to the major facilitator superfamily (MFS) are widely distributed in microbial genomes and exhibit a large spectrum of substrate specificities. Multidrug MFS efflux pumps are present either as single-component transporters or as tripartite complexes. In this review, we will summarize how the multidrug MFS efflux pumps contribute to the interplay between bacteria and targeted host cells, with emphasis on their role in bacterial virulence, in the colonization of plant and animal host cells and in biofilm formation. We will also address the complexity of these interactions in the light of the underlying regulatory networks required for the effective activation of efflux pump genes

A machine learning approach to estimating preterm infants survival: development of the Preterm Infants Survival Assessment (PISA) predictor

Estimation of mortality risk of very preterm neonates is carried out in clinical and research settings. We aimed at elaborating a prediction tool using machine learning methods. We developed models on a cohort of 23747 neonates <30 weeks gestational age, or <1501 g birth weight, enrolled in the Italian Neonatal Network in 2008–2014 (development set), using 12 easily collected perinatal variables. We used a cohort from 2015–2016 (N = 5810) as a test set. Among several machine learning methods we chose artificial Neural Networks (NN). The resulting predictor was compared with logistic regression models. In the test cohort, NN had a slightly better discrimination than logistic regression (P < 0.002). The differences were greater in subgroups of neonates (at various gestational age or birth weight intervals, singletons). Using a cutoff of death probability of 0.5, logistic regression misclassified 67/5810 neonates (1.2 percent) more than NN. In conclusion our study – the largest published so far – shows that even in this very simplified scenario, using only limited information available up to 5 minutes after birth, a NN approach had a small but significant advantage over current approaches. The software implementing the predictor is made freely available to the community

The EPFL Logic Synthesis Libraries

We present a collection of modular open source C++ libraries for the development of logic synthesis applications. These libraries can be used to develop applications for the design of classical and emerging technologies, as well as for the implementation of quantum compilers. All libraries are well documented and well tested. Furthermore, being header-only, the libraries can be readily used as core components in complex logic synthesis systems.Comment: 11 pages, originally accepted at Int'l Workshop on Logic & Synthesis 2018, extended for Workshop on Open-Source EDA Technology 201

Low Power 3D Serial TSV Link for High Bandwidth Cross-Chip Communication

3D-ICs based on TSV technology provide high bandwidth inter-chip connections. The drawback is that most of the existing TSVs consume a large amount of silicon real estate. We present circuit-level design and analysis of area efficient, low power, high-data-rate 3D serial TSV links. A design space exploration is performed and trade-offs in terms of area, power and performance are presented. Circuit simulations of RC-extracted layouts in 40nm CMOS-technology reveals that 8:1 serialization efficiently balances area consumption and energy efficiency. Using 10μm-diameter TSV technology, an 8Gb/s serial link consumes only 84fJ/bit with 10X area reduction over 8b parallel bus

The Anti-Arthritic Efficacy of Khellin Loaded in Ascorbyl Decanoate Nanovesicles after an Intra-Articular Administration

Osteoarthritis is the most widespread joint-affecting disease. The management of persistent pain remains inadequate and demands new therapeutic strategies. In this study, we explored the pain relieving and protective properties of a single intra-articular (i.a.) injection of khellin loaded in nanovesicles (K-Ves) based on ascorbyl decanoate plus phosphatidylcholine in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) treatment. The developed nanovesicles (approximately 136 nm) had a narrow size distribution (PdI 0.26), a good recovery (about 80%) and a worthy encapsulation efficiency (about 70%) with a ζ-potential of about −40 mV. The stability of K-Ves was assessed in simulated synovial fluid. Seven days after the articular damage with MIA, both K-Ves and a suspension of khellin (K, 50 μL) were i.a. injected. K-Ves significantly counteracted MIA-induced hypersensitivity to mechanical noxious (paw pressure test) and non-noxious stimuli (von Frey test) and significantly reduced the postural unbalance related to spontaneous pain (incapacitance test) and the motor alterations (beam balance test) 7 and 14 days after the i.a. injection. K was partially active only on day 7 after the treatment. The histology emphasized the improvement of several morphological factors in MIA plus K-Ves-treated animals. In conclusion, K-Ves could be successfully used for the local treatment of osteoarthritis

A Best-Fit Mapping Algorithm to Facilitate ESOP-Decomposition in Clifford+T Quantum Network Synthesis

Currently, there is a large research interest and a significant economical effort to build the first practical quantum computer. Such quantum computers promise to exceed the capabilities of conventional computers in fields such as computational chemistry, machine learning and cryptanalysis. Automated methods to map logic designs to quantum networks are crucial to fully realizing this dream, however, existing methods can be expensive both in computational time as well as in the size of the resultant quantum networks. This work introduces an efficient method to map reversible single-target gates into a universal set of quantum gates (Clifford+T). This mapping method is called best-fit mapping and aims at reducing the cost of the resulting quantum network. It exploits k-LUT mapping and the existence of clean ancilla qubits to decompose a large single-target gate into a set of smaller single-target gates. In addition this work proposes a post-synthesis optimization method to reduce the cost of the final quantum network, based on two cost-minimization properties. Results show a cost reduction for the synthesized EPFL benchmark up to 53% in the number T gates

Unraveling pedestrian mobility on a road network using ICTs data during great tourist events

Tourist flows in historical cities are continuously growing in a globalized world and adequate governance processes, politics and tools are necessary in order to reduce impacts on the urban livability and to guarantee the preservation of cultural heritage. The ICTs offer the possibility of collecting large amount of data that can point out and quantify some statistical and dynamic properties of human mobility emerging from the individual behavior and referring to a whole road network. In this paper we analyze a new dataset that has been collected by the Italian mobile phone company TIM, which contains the GPS positions of a relevant sample of mobile devices when they actively connected to the cell phone network. Our aim is to propose innovative tools allowing to study properties of pedestrian mobility on the whole road network. Venice is a paradigmatic example for the impact of tourist flows on the resident life quality and on the preservation of cultural heritage. The GPS data provide anonymized georeferenced information on the displacements of the devices. After a filtering procedure, we develop specific algorithms able to reconstruct the daily mobility paths on the whole Venice road network. The statistical analysis of the mobility paths suggests the existence of a travel time budget for the mobility and points out the role of the rest times in the empirical relation between the mobility time and the corresponding path length. We succeed to highlight two connected mobility subnetworks extracted from the whole road network, that are able to explain the majority of the observed mobility. Our approach shows the existence of characteristic mobility paths in Venice for the tourists and for the residents. Moreover the data analysis highlights the different mobility features of the considered case studies and it allows to detect the mobility paths associated to different points of interest. Finally we have disaggregated the Italian and foreigner categories to study their different mobility behaviors

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

Shedding light on typical species : implications for habitat monitoring

Habitat monitoring in Europe is regulated by Article 17 of the Habitats Directive, which suggests the use of typical species to assess habitat conservation status. Yet, the Directive uses the term “typical” species but does not provide a definition, either for its use in reporting or for its use in impact assessments. To address the issue, an online workshop was organized by the Italian Society for Vegetation Science (SISV) to shed light on the diversity of perspectives regarding the different concepts of typical species, and to discuss the possible implications for habitat monitoring. To this aim, we inquired 73 people with a very different degree of expertise in the field of vegetation science by means of a tailored survey composed of six questions. We analysed the data using Pearson's Chi-squared test to verify that the answers diverged from a random distribution and checked the effect of the degree of experience of the surveyees on the results. We found that most of the surveyees agreed on the use of the phytosociological method for habitat monitoring and of the diagnostic and characteristic species to evaluate the structural and functional conservation status of habitats. With this contribution, we shed light on the meaning of “typical” species in the context of habitat monitoring