Evolution of transport under cumulative damage in metro systems

One dominant aspect of cities is transport and massive passenger mobilization which remains a challenge with the increasing demand on the public as cities grow. In addition, public transport infrastructure suffers from traffic congestion and deterioration, reducing its efficiency. In this paper, we study the capacity of transport in 33 worldwide metro systems under the accumulation of damage. We explore the gradual reduction of functionality in these systems associated with damage that occurs stochastically. The global transport of each network is modeled as the diffusive movement of Markovian random walkers on networks considering the capacity of transport of each link, where these links are susceptible to damage. Monte Carlo simulations of this process in metro networks show the evolution of the functionality of the system under damage considering all the complexity in the transportation structure. This information allows us to compare and classify the effect of damage in metro systems. Our findings provide a general framework for the characterization of the capacity to maintain the transport under failure in different systems described by networks.Comment: 9 pages; 4 figure

Identification of gastric cancer from speckle patterns

Speckle technique is based on the light intensity distribution randomly formed when a laser light is reflected on a rough surface, creating a pattern of illuminated grains (constructively) and dark (destructive) on scales of 1 μm. When the samples are displaced or deformed, the speckle pattern is altered. In this paper we present speckle patterns obtained from samples of gastric mucosa that is physically altered for the carcinogenesis process. Biopsies were studied with different diagnoses and were grouped according to the characteristics of speckle patterns. Speckle patterns were obtained by illuminating the samples with green laser. Morphological parameters of the speckle patterns reveal existence of 3 descriptors: the average grain size, hydraulic radius and the radio of the Weddel disc, which showed a high, intermediate and low value. The comparison shows agreement between the histopathological diagnosis and the values obtained by the speckle technique, making this technique emerge as a new classification system for quantitative diagnosis of precancerous lesions.Facultad de Ingenierí

Identification of gastric cancer from speckle patterns

Speckle technique is based on the light intensity distribution randomly formed when a laser light is reflected on a rough surface, creating a pattern of illuminated grains (constructively) and dark (destructive) on scales of 1 μm. When the samples are displaced or deformed, the speckle pattern is altered. In this paper we present speckle patterns obtained from samples of gastric mucosa that is physically altered for the carcinogenesis process. Biopsies were studied with different diagnoses and were grouped according to the characteristics of speckle patterns. Speckle patterns were obtained by illuminating the samples with green laser. Morphological parameters of the speckle patterns reveal existence of 3 descriptors: the average grain size, hydraulic radius and the radio of the Weddel disc, which showed a high, intermediate and low value. The comparison shows agreement between the histopathological diagnosis and the values obtained by the speckle technique, making this technique emerge as a new classification system for quantitative diagnosis of precancerous lesions.Facultad de Ingenierí

Improving quality of care and clinical outcomes for rectal cancer through clinical audits in a multicentre cancer care organisation

Introduction: Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. Methods: Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. Results: Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p < 0.001). Conclusions: The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time

Impact of non-adherence to radiotherapy on 1-year survival in cancer patients in Catalonia, Spain

This study aims to assess the effects of non-adherence to external beam radiation therapy in cancer patients receiving treatment with a curative. This retrospective cohort study collected health records data for all cancer patients treated with external beam radiotherapy with curative intent in 2016 in Catalonia, Spain. Adherence was defined as having received at least 90% of the total dose prescribed. A logistic regression model was used to assess factors related to non-adherence, and its association with one-year survival was evaluated using Cox regression. The final sample included 8721 patients (mean age 63.6 years): breast cancer was the most common tumour site (38.1%), followed by prostate and colon/rectum. Treatment interruptions prolonged the total duration of therapy in 70.7% of the patients, and 1.0% were non-adherent. Non-adherence was associated with advanced age, female gender, and some localization of primary tumour (head and neck, urinary bladder, and haematological cancers). The risk of death in non-adherent patients was higher than in adherent patients (hazard ratio [HR] 1.63, 95% confidence interval 0.97-2.74), after adjusting for the potential confounding effect of age, gender, tumour site and comorbidity. Non-adherence to radiotherapy, as measured by the received dose, is very low in our setting, and it may have an impact on one-year survival

Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

Identification of gastric cancer from speckle patterns

Speckle technique is based on the light intensity distribution randomly formed when a laser light is reflected on a rough surface, creating a pattern of illuminated grains (constructively) and dark (destructive) on scales of 1 μm. When the samples are displaced or deformed, the speckle pattern is altered. In this paper we present speckle patterns obtained from samples of gastric mucosa that is physically altered for the carcinogenesis process. Biopsies were studied with different diagnoses and were grouped according to the characteristics of speckle patterns. Speckle patterns were obtained by illuminating the samples with green laser. Morphological parameters of the speckle patterns reveal existence of 3 descriptors: the average grain size, hydraulic radius and the radio of the Weddel disc, which showed a high, intermediate and low value. The comparison shows agreement between the histopathological diagnosis and the values obtained by the speckle technique, making this technique emerge as a new classification system for quantitative diagnosis of precancerous lesions.Facultad de Ingenierí

New Pathogenesis Mechanisms and Translational Leads Identified by Multidimensional Analysis of Necrotizing Myositis in Primates

A fundamental goal of contemporary biomedical research is to understand the molecular basis of disease pathogenesis and exploit this information to develop targeted and more-effective therapies. Necrotizing myositis caused by the bacterial pathogen Streptococcus pyogenes is a devastating human infection with a high mortality rate and few successful therapeutic options. We used dual transcrip-tome sequencing (RNA-seq) to analyze the transcriptomes of S. pyogenes and host skeletal muscle recovered contemporaneously from infected nonhuman primates. The in vivo bacterial transcriptome was strikingly remodeled compared to organisms grown in vitro, with significant upregulation of genes contributing to virulence and altered regulation of metabolic genes. The transcriptome of muscle tissue from infected nonhuman primates (NHPs) differed significantly from that of mock-infected animals, due in part to substantial changes in genes contributing to inflammation and host defense processes. We discovered significant positive correlations between group A streptococcus (GAS) virulence factor transcripts and genes involved in the host immune response and inflammation. We also discovered significant correlations between the magnitude of bacterial virulence gene expression in vivo and pathogen fitness, as assessed by previously conducted genome-wide transposon-directed insertion site sequencing (TraDIS). By integrating the bacterial RNA-seq data with the fitness data generated by TraDIS, we discovered five new pathogen genes, namely, S. pyogenes 0281 (Spy0281 [dahA]), ihk-irr, slr, isp, and ciaH, that contribute to necrotizing myositis and confirmed these findings using isogenic deletion-mutant strains. Taken together, our study results provide rich new information about the molecular events occurring in severe invasive infection of primate skeletal muscle that has extensive translational research implications. IMPORTANCE Necrotizing myositis caused by Streptococcus pyogenes has high morbidity and mortality rates and relatively few successful therapeutic options. In addition, there is no licensed human S. pyogenes vaccine. To gain enhanced understanding of the molecular basis of this infection, we employed a multidimensional analysis strategy that included dual RNA-seq and other data derived from experimental infection of nonhuman primates. The data were used to target five streptococcal genes for pathogenesis research, resulting in the unambiguous demonstration that these genes contribute to pathogen-host molecular interactions in necrotizing infections. We exploited fitness data derived from a recently conducted genome-wide transposon mutagenesis study to discover significant correlation between the magnitude of bacterial virulence gene expression in vivo and pathogen fitness. Collectively, our findings have significant implications for translational research, potentially including vaccine efforts.Peer reviewe

Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague

The bacterial pathogenYersinia pestisgave rise to devastating outbreaks throughouthuman history, and ancient DNA evidence has shown it afflicted human populations asfar back as the Neolithic.Y. pestisgenomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to itsemergence from aYersinia pseudotuberculosis-like progenitor; however, the number ofreconstructed LNBA genomes are too few to explore its diversity during this criticalperiod of development. Here, we present 17Y. pestisgenomes dating to 5,000 to 2,500y BP from a wide geographic expanse across Eurasia. This increased dataset enabled usto explore correlations between temporal, geographical, and genetic distance. Ourresults suggest a nonflea-adapted and potentially extinct single lineage that persistedover millennia without significant parallel diversification, accompanied by rapid dis-persal across continents throughout this period, a trend not observed in other pathogensfor which ancient genomes are available. A stepwise pattern of gene loss provides fur-ther clues on its early evolution and potential adaptation. We also discover the presenceof theflea-adapted form ofY. pestisin Bronze Age Iberia, previously only identified inin the Caucasus and the Volga regions, suggesting a much wider geographic spread ofthis form ofY. pestis. Together, these data reveal the dynamic nature of plague’s forma-tive years in terms of its early evolution and ecology

Down-regulation of four putative arabinoxylan feruloyl transferase genes from family PF02458 reduces ester-linked ferulate content in rice cell walls

Industrial processes to produce ethanol from lignocellulosic materials are available, but improved efficiency is necessary to make them economically viable. One of the limitations for lignocellulosic conversion to ethanol is the inaccessibility of the cellulose and hemicelluloses within the tight cell wall matrix. Ferulates (FA) can cross-link different arabinoxylan molecules in the cell wall of grasses via diferulate and oligoferulate bridges. This complex cross-linking is thought to be a key factor in limiting the biodegradability of grass cell walls and, therefore, the reduction in FA is an attractive target to improve enzyme accessibility to cellulose and hemicelluloses. Unfortunately, our knowledge of the genes responsible for the incorporation of FA to the cell wall is limited. A bioinformatics prediction based on the gene similarities and higher transcript abundance in grasses relative to dicot species suggested that genes from the pfam family PF02458 may act as arabinoxylan feruloyl transferases. We show here that the FA content in the cell walls and the transcript levels of rice genes Os05g08640, Os06g39470, Os01g09010 and Os06g39390, are both higher in the stems than in the leaves. In addition, an RNA interference (RNAi) construct that simultaneously down-regulates transcript levels of these four genes is associated with a significant reduction in FA of the cell walls from the leaves of the transgenic plants relative to the control (19% reduction, P < 0.0001). Therefore, our experimental results in rice support the bioinformatics prediction that members of family PF02458 are involved in the incorporation of FA into the cell wall in grasses