A low kickback fully differential dynamic comparator for pipeline analog-to-digital converters

This study presents a fully differential dynamic comparator with low kickback noise, an effect caused by voltage variations in the regeneration nodes of these types of circuit. Given their low power dissipation, dynamic comparators are key circuits in analog-to-digital converters (ADCs), especially in pipelined ADCs. The proposed comparator has been simulated and compared with three other comparator topologies. The value of the kickback noise generated by the proposed circuit is lower than that generated by other conventional dynamic comparators over a wide input range, while simultaneously showing a low offset voltage error. The dynamic comparator has been implemented in a low-resolution ADC with a resolution of 2.5 effective bits, which has been prototyped in a 0.35-m CMOS AMS C35B4 process. Its size is 34 m × 38 m.This work has been partially funded by Spanish government projects TEC2015‐66878‐C3‐2‐R (MINECO/FEDER, UE) and RTI2018‐097088‐B‐C33 (MINECO/FEDER, UE)

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks : A retrospective, observational, multicentre study by the Spanish Psoriasis Group

Altres ajuts: Acord transformatiu CRUE-CSICData on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (−9.3; [−10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value

Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity

Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity

Primers resultats dels estudis dels elements marmoris del jaciment de l'Antiguitat Tardana del Plan de ses Figueres de l'illa de Cabrera

El Pla de ses Figueres és un jaciment que es troba a la riba del port de Cabrera, una petita illa de 1.836 ha. situada en el sud de les illes Balears. Diversos treballs de prospecció i d’excavació han donat a conèixer una important ocupació humana del lloc centrada en els segles V a VII dC. A les zones intervingudes s’han identificat una factoria de salaons, un possible taller de producció de porpra i una necròpoli. En el present treball s’exposaran set peces de marbre localitzades en dit jaciment dintre del projecte “Recuperació, consolidació i museïtzació del monestir bizantí de l’illa de Cabrera”, el qual ja fa dotze anys que finança ininterrompudament l’Ajuntament de Palma.El Pla de ses Figueres is an archaeological site located next to the harbour of Cabrera, a small island of 1.836ha situated in the south of the Balearic Islands group. Several field surveys and archaeological excavations have brought into light the important human occupation of this place between the 5th and the 7th centuries AD. At the pieces of land excavated so far, a salting (food-processing) area, a possible workshop for the production of purple and a necropolis have been identified. In this work we present seven fragments of objects made with white and coloured marbles that were found in this site during the excavations undertaken within the project funded by the Town Council of Palma de Mallorca

Pseudomonas aeruginosa adaptation in cystic fibrosis patients increases C5a levels and promotes neutrophil recruitment

10p.-5 fig.-1 tab.Cystic fibrosis (CF) disease is characterized by an intense airway inflammatory response mediated by neutrophils and chronic respiratory infections caused by P. aeruginosa. High levels of the complement component C5a, the strongest neutrophil chemoattractant molecule, are commonly found in the CF lung and have been associated with a worsening of the disease. In this study, we investigated how the isolates from CF patients modulate the levels of C5a and identified the bacterial factors involved. We demonstrated that most isolates from airway chronic infections induce the production and accumulation of C5a, an effect attributable to the loss of C5a cleavage by the exoproteases alkaline protease (AprA) and elastase B (LasB). Furthermore, we found that lack of the bacterial protease-dependent C5a degradation is due to mutations in the master regulator LasR. Thus, complementation of a non-C5a-cleaving CF isolate with a functional wild-type LasR restored its ability to express both proteases, cleave C5a and reduce neutrophil recruitment in vitro. These findings suggest that the non-cleaving C5a phenotype acquired by the LasR variants frequently isolated in CF patients may account for the strong neutrophilia and general neutrophil dysfunction predisposing toward increased inflammation and reduced bacterial clearance described in CF patients.This work was supported by the Spanish Ministry of Science and Innovation and European Regional Development Fund (FEDER) under Grant RTI2018-100701-B-100 to SA and RTI2018-102242-B-I00 to MCV, and by the Comunidad de Madrid under Grant S2017/BMD-3673 to MCV.Peer reviewe

Effects of Macromolecular Crowding on the Inhibition of Virus Assembly and Virus-Cell Receptor Recognition

Biological fluids contain a very high total concentration of macromolecules that leads to volume exclusion by one molecule to another. Theory and experiment have shown that this condition, termed macromolecular crowding, can have significant effects on molecular recognition. However, the influence of molecular crowding on recognition events involving virus particles, and their inhibition by antiviral compounds, is virtually unexplored. Among these processes, capsid self-assembly during viral morphogenesis and capsid-cell receptor recognition during virus entry into cells are receiving increasing attention as targets for the development of new antiviral drugs. In this study, we have analyzed the effect of macromolecular crowding on the inhibition of these two processes by peptides. Macromolecular crowding led to a significant reduction in the inhibitory activity of: 1), a capsid-binding peptide and a small capsid protein domain that interfere with assembly of the human immunodeficiency virus capsid, and 2), a RGD-containing peptide able to block the interaction between foot-and-mouth disease virus and receptor molecules on the host cell membrane (in this case, the effect was dependent on the conditions used). The results, discussed in the light of macromolecular crowding theory, are relevant for a quantitative understanding of molecular recognition processes during virus infection and its inhibition

Image_1_Factor H-related protein 1 promotes complement-mediated opsonization of Pseudomonas aeruginosa.jpeg

Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator that inactivates C3b, preventing the formation of the C3-convertase and complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere in this bacterial mechanism of resisting complement. Here, we show that FHR-1 binds to P. aeruginosa via the outer membrane protein OprG in a lipopolysaccharide (LPS) O antigen-dependent manner. Binding assays with purified components or with FHR-1-deficient serum supplemented with FHR-1 show that FHR-1 competes with FH for binding to P. aeruginosa. Blockage of FH binding to C3b deposited on the bacteria reduces FH-mediated cofactor activity of C3b degradation, increasing the opsonization of the bacteria and the formation of the potent chemoattractant C5a. Overall, our findings indicate that FHR-1 is a host factor that promotes complement activation, facilitating clearance of P. aeruginosa by opsonophagocytosis.</p