Analysis on relationship between extreme pathways and correlated reaction sets

Background: Constraint-based modeling of reconstructed genome-scale metabolic networks has been successfully applied on several microorganisms. In constraint-based modeling, in order to characterize all allowable phenotypes, network-based pathways, such as extreme pathways and elementary flux modes, are defined. However, as the scale of metabolic network rises, the number of extreme pathways and elementary flux modes increases exponentially. Uniform random sampling solves this problem to some extent to study the contents of the available phenotypes. After uniform random sampling, correlated reaction sets can be identified by the dependencies between reactions derived from sample phenotypes. In this paper, we study the relationship between extreme pathways and correlated reaction sets.Results: Correlated reaction sets are identified for E. coli core, red blood cell and Saccharomyces cerevisiae metabolic networks respectively. All extreme pathways are enumerated for the former two metabolic networks. As for Saccharomyces cerevisiae metabolic network, because of the large scale, we get a set of extreme pathways by sampling the whole extreme pathway space. In most cases, an extreme pathway covers a correlated reaction set in an \u27all or none\u27 manner, which means either all reactions in a correlated reaction set or none is used by some extreme pathway. In rare cases, besides the \u27all or none\u27 manner, a correlated reaction set may be fully covered by combination of a few extreme pathways with related function, which may bring redundancy and flexibility to improve the survivability of a cell. In a word, extreme pathways show strong complementary relationship on usage of reactions in the same correlated reaction set.Conclusion: Both extreme pathways and correlated reaction sets are derived from the topology information of metabolic networks. The strong relationship between correlated reaction sets and extreme pathways suggests a possible mechanism: as a controllable unit, an extreme pathway is regulated by its corresponding correlated reaction sets, and a correlated reaction set is further regulated by the organism\u27s regulatory network.<br /

Intrusion Detection System by Fuzzy Interpolation

Network intrusion detection systems identify malicious connections and thus help protect networks from attacks. Various data-driven approaches have been used in the development of network intrusion detection systems, which usually lead to either very complex systems or poor generalization ability due to the complexity of this challenge. This paper proposes a data-driven network intrusion detection system using fuzzy interpolation in an effort to address the aforementioned limitations. In particular, the developed system equipped with a sparse rule base not only guarantees the online performance of intrusion detection, but also allows the generation of security alerts from situations which are not directly covered by the existing knowledge base. The proposed system has been applied to a well-known data set for system validation and evaluation with competitive results generated

The Grizzly, April 21, 2016

Writers, Editors Debut Lantern • Re-vote Results in Rein and Thomas Winning Election • Politics Professor Publishes Book Review in Wall Street Journal • International Perspective: Balancing Changes During Freshman Year • Transgender Student Overcomes Challenges • Ursinus\u27 UCEA Goes Green • Opinions: Laws Addressing Pornography Must Adapt; Film Review: Batman v. Superman Rates 3 / 10 • Playing Big • What the Masters Means to Me • My Golden Friendship with The Bronze Titanhttps://digitalcommons.ursinus.edu/grizzlynews/1690/thumbnail.jp

Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an alternative strategy for treatment of multiple cancers

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Thematic relations outperform taxonomic relations in a cued recall task

Prior knowledge has long been known to influence retention of newly experienced information. In particular, known semantic associations across items facilitate subsequent memory for these items, and this effect has been shown to increase with measures of semantic relatedness. In the field of categories and concepts, the processing of taxonomic (e.g., cup-fork, dog-bird) versus thematic (e.g., cup-drink, dog-leash) conceptual relations can be differentiated at the behavioral and neural levels. However, the effects of these distinct conceptual relations on memory remain unresolved. The current study used a stimulus set consisting of thematic, taxonomic, and unrelated noun-noun word pairs, to shed light on this issue. Our results indicate that pairs with thematic relations lead to improved cued memory performance, followed by taxonomic relations, and finally unrelated pairs. This study provides evidence that conceptual relations differ in the extent to which they facilitate cued memory performance

Systematic review of trimodality therapy for patients with malignant pleural mesothelioma

Background: Malignant pleural mesothelioma (MPM) is an aggressive form of cancer arising from the pleural mesothelium. Trimodality therapy (TMT) involving extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy is a recognized treatment option with a curative intent. Despite encouraging results from institutional studies, TMT in the treatment of MPM remains controversial. The present systematic review aims to assess the safety and efficacy of TMT in the current literature. Methods: A systematic review was performed using five electronic databases from 1 January 1985 to 1 October 2012. Studies were selected independently by two reviewers according to predefined selection criteria. The primary endpoint was overall survival. Secondary endpoints included disease-free survival, disease recurrence, perioperative morbidity and length of stay. Results: Sixteen studies were included for quantitative assessment, including one randomized controlled trial and five prospective series. Median overall survival ranged from 12.8-46.9 months. Disease-free survival ranged from 10-16.3 months. Perioperative mortality ranged from 0-12.5%. Overall perioperative morbidity ranged from 50-82.6% and the average length of stay was 9-14 days. Conclusions: Outcomes of patients who underwent TMT in the current literature appeared to be inconsistent. Four prospective series involving a standardised treatment regimen with neoadjuvant chemotherapy indicated encouraging results based on intention-to-treat analysis. However, a small study assessing the feasibility of conducting a randomized controlled trial for TMT versus conservative treatment reported poor short- and long-term outcomes for patients who underwent pneumonectomy. Overall, results of the present systematic review suggest TMT may offer acceptable perioperative outcomes and long-term survival in selected patients treated in specialized centers.10 page(s

GNSS Interferometric Reflectometry measurements of sea levels and wave height at E. B. Scripps Pier, California

Modeling the transfer of energy from the open ocean to the coast (e.g. waves, storm surge) is challenging but of critical importance for assessing the impacts of climate change and sea level rise. In particular, the sparsity of wave and tide gauges makes it difficult to calibrate these types of models. GNSS Interferometric Reflectometry (GNSS-IR), although it has lower accuracy, constitutes an attractive alternative for sensing nearshore surface properties because of its low deployment costs. We evaluate the accuracy of GNSS-IR measuring long-period sea level variations and short-period wave heights by running a 4-month experiment at the E. B. Scripps Pier, in La Jolla, California. We use a standard GNSS geodetic right hand circularly polarized choke ring antenna to capture the GPS, GLONASS and Galileo constellations, allowing more measurements than GPS alone. For low satellite elevation angles, the captured signals result from interference between the direct signal and the coherent reflection from the sea surface, while above a certain elevation angle threshold, there is interference with an incoherent reflection depending on wave height. We use the coherent reflection interference to measure sea level variations, presenting RMS differences of 18 cm with respect to a conventional tide gauge record. The differences are of high-frequency, so long-period variations and tidal constituents are measured with acceptable accuracy as compare to traditional instruments. The incoherent reflection at large elevation angles is employed to determine short-period wave heights, which we demonstrate for the first time using a standard antenna. Adopting the Rayleigh criterion, we relate the significant wave height (Hs) to the elevation angle threshold in which the interfering reflection changes from coherent to incoherent. We propose a criterion to determine the elevation angle threshold that retrieves Hs with low dispersion. The GNSS-derived Hs have RMS differences of 14 cm with respect to a conventional wave gauge. Hence, a calibration period, for example with a movable buoy, combined with the elevation angle threshold criterion can be employed to retrieve Hs. Our results demonstrate that GNSS-IR is a valid alternative for sensing sea state when traditional instruments are nonexistent