A Risky enterprise: the Aldine edition of Galen, the failures of the editors, and the shadow of Erasmus of Rotterdam

The Aldine edition of Galen, awaited for more than 25 years, was perhaps the most risky enterprise in the whole history of the publishing house, and it almost brought Aldus’ heirs to bankruptcy. Although the editors were among the most renowned specialists of the time, the edition was harshly criticized by one former friend and collaborator of Aldus, Desiderius Erasmus of Rotterdam. Why? Was the edition so bad, were the manuscripts on which the edition was based responsible for its quality? Or were there other reasons for Erasmus’ complaint? The paper tries to give some hints in order to answer such questions, arguing that the role of Erasmus in the assessment of the value of the edition should take us into Aldus’ house in the period of the late fifteenth and early sixteenth century, and into the political and religious debate of the time

On the Properties of a Bundle of Flexible Actin Filaments in an Optical Trap

We establish the Statistical Mechanics framework for a bundle of Nf living and uncrosslinked actin filaments in a supercritical solution of free monomers pressing against a mobile wall. The filaments are anchored normally to a fixed planar surface at one of their ends and, because of their limited flexibility, they grow almost parallel to each other. Their growing ends hit a moving obstacle, depicted as a second planar wall, parallel to the previous one and subjected to a harmonic compressive force. The force constant is denoted as trap strength while the distance between the two walls as trap length to make contact with the experimental optical trap apparatus. For an ideal solution of reactive filaments and free monomers at fixed free monomers chemical potential, we obtain the general expression for the grand potential from which we derive averages and distributions of relevant physical quantities, namely the obstacle position, the bundle polymerization force and the number of filaments in direct contact with the wall. The grafted living filaments are modeled as discrete Wormlike chains, with Factin persistence length, subject to discrete contour length variations to model single monomer (de)polymerization steps. Rigid filaments, either isolated or in bundles, all provide average values of the stalling force in agreement with Hill's predictions, independent of the average trap length. Flexible filaments instead, for values of the trap strength suitable to prevent their lateral escape, provide an average bundle force and an average trap length slightly larger than the corresponding rigid cases (few percents). Still the stalling force remains nearly independent on the average trap length, but results from the product of two strongly L dependent contributions: the fraction of touching filaments and the single filament buckling force.Comment: 21 pages, 8 figure

A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer

Up to 20% of colorectal cancer (CRC) node-negative patients develop loco-regional or distant recurrences within 5 years from surgery. No predictive biomarker able to identify the node-negative subjects at high risk of relapse after curative treatment is presently available.Forty-eight localized (i.e. stage I-II) colon cancer patients who underwent radical tumor resection were considered. The expression of five miRNAs, involved in CRC progression, was investigated by qRT-PCR in both tumor tissue and matched normal colon mucosa.Interestingly, we found that the coordinate deregulation of four miRNAs (i.e. miR-18a, miR-21, miR-182 and miR-183), evaluated in the normal mucosa adjacent to tumor, is predictive of relapse within 55 months from curative surgery.Our results, if confirmed in independent studies, may help to identify high-risk patients who could benefit most from adjuvant therapy. Moreover, this work highlights the importance of extending the search for tissue biomarkers also to the tumor-adjacent mucosa

A Novel Approach for an Integrated Straw tube-Microstrip Detector

We report on a novel concept of silicon microstrips and straw tubes detector, where integration is accomplished by a straw module with straws not subjected to mechanical tension in a Rohacell $^{\circledR}$ lattice and carbon fiber reinforced plastic shell. Results on mechanical and test beam performances are reported on as well.Comment: Accepted by Transactions on Nuclear Science (2005). 11 pages, 9 figures, uses lnfprep.st

PV Cell Characteristic Extraction to Verify Power Transfer Efficiency in Indoor Harvesting System

A method is proposed to verify the efficiency of low-power harvesting systems based on Photovoltaic (PV) cells for indoor applications and a Fractional Open-Circuit Voltage (FOCV) technique to track the Maximum Power Point (MPP). It relies on an algorithm to reconstruct the PV cell Power versus Voltage (P-V) characteristic measuring the open circuit voltage and the voltage/current operating point but not the short-circuit current as required by state-of-the-art algorithms. This way the characteristic is reconstructed starting from the two values corresponding to standard operation modes of dc-dc converters implementing the FOCV Maximum Power Point Tracking (MPPT) technique. The method is applied to a prototype system: an external board is connected between the transducer and the dc-dc converter to measure the open circuit voltage and the voltage/current operating values. Experimental comparisons between the reconstructed and the measured P-V characteristics validate the reconstruction algorithm. Experimental results show the method is able to clearly identify the error between the transducer operating point and the one corresponding to the maximum power transfer, whilst also suggesting corrective action on the programmable factor of the FOCV technique. The proposed technique therefore provides a possible way of estimating MPPT efficiency without sampling the full P-V characteristic

Characterization and genome sequencing of a Citrobacter freundii phage CfP1 harboring a lysin active against multidrug-resistant isolates

Citrobacter spp., although frequently ignored, is emerging as an important nosocomial bacterium able to cause various superficial and systemic life-threatening infections. Considered to be hard-to-treat bacterium due to its pattern of high antibiotic resistance, it is important to develop effective measures for early and efficient therapy. In this study, the first myovirus (vB_CfrM_CfP1) lytic for Citrobacter freundii was microbiologically and genomically characterized. Its morphology, activity spectrum, burst size, and biophysical stability spectrum were determined. CfP1 specifically infects C. freundii, has broad host range (>85 %; 21 strains tested), a burst size of 45 PFU/cell, and is very stable under different temperatures (20 to 50 °C) and pH (3 to 11) values. CfP1 demonstrated to be highly virulent against multidrug-resistant clinical isolates up to 12 antibiotics, including penicillins, cephalosporins, carbapenems, and fluroquinoles. Genomically, CfP1 has a dsDNA molecule with 180,219 bp with average GC content of 43.1 % and codes for 273 CDSs. The genome architecture is organized into function-specific gene clusters typical for tailed phages, sharing 46 to 94 % nucleotide identity to other Citrobacter phages. The lysin gene encoding a predicted D-Ala-D-Ala carboxypeptidase was also cloned and expressed in Escherichia coli and its activity evaluated in terms of pH, ionic strength, and temperature. The lysine optimum activity was reached at 20 mM HEPES, pH 7 at 37 °C, and was able to significantly reduce all C. freundii (>2 logs) as well as Citrobacter koseri (>4 logs) strains tested. Interestingly, the antimicrobial activity of this enzyme was performed without the need of pretreatment with outer membrane-destabilizing agents. These results indicate that CfP1 lysin is a good candidate to control problematic Citrobacter infections, for which current antibiotics are no longer effective.This study was funded by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER006684), and the PhD grants SFRH/BPD/111653/2015 and SFRH/BPD/69356/2010

OXA-carbapenemases and mutations within PBPs in ST2 carbapenem-resistant A. baumannii: Evaluating the efficacy of cefiderocol and ampicillin-sulbactam combination therapy

Objectives: Carbapenem-resistant Acinetobacter baumannii (A. baumannii; CRAB) isolates represent a serious public health concern. Recently, a novel molecule, the cefiderocol (FDC), has emerged as a promising therapeutic option for CRAB infections. In the present study, we analysed the genomes of five A. baumannii ST2 isolates from four hospitalized patients. All patients were treated with FDC and an ampicillin/sulbactam (AMP/SUL) combination. Methods: Whole-genome sequencing of the five CRAB isolates was performed using an Illumina MiSeq instrument. A detailed bioinformatic analysis was carried out to acquire information about genotyping, antimicrobial resistance genes (ARGs), virulence associated genes (VAGs), single nucleotide polymorphisms (SNPs), and the phylogenetic tree of the five CRAB isolates. Results: Among the five CRAB isolates, only three (Ab.2, Ab.3, and Ab.4) exhibited resistance to FDC. The genomes of all isolates were highly similar, and multilocus sequence typing (MLST) analysis indicated they all belong to sequence type 2 (ST2), corresponding to international clone 2. Phylogenetic analysis suggests that isolates Ab.2, Ab.3, and Ab.4 may share a common ancestor or be linked by a possible transmission event. In contrast, isolates Ab.1 and Ab.5 were more divergent from the other three. Nevertheless, all five isolates harboured the same ARGs and VAGs. The OXA-23, OXA-66, and ADC-25 β-lactamases were detected in all strains. The FDC-non-susceptible isolates showed a K235N/H370Y double mutation within PBP3, along with a G370C substitution in PBP1a. Conclusions: The four clinical cases described in this study represent an important example of the efficacy and good practice of FDC plus AMP/SUL combination in the treatment of critical patients suffering from CRAB infections. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy