bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulating urban growth in a megalopolitan area using a patch‐based cellular automata
Authors: Alaei Moghadam Sanaz , Karimi Mohammad , Habibi Kyoumars 
Published: January 2018

AbstractAlthough traditional cellular automata (CA)‐based models can effectively simulate urban land‐use changes, they typically ignore the spatial evolution of urban patches, due to their use of cell‐based simulation strategies. This research proposes a new patch‐based CA model to incorporate a spatial constraint based on the growth patterns of urban patches into the conventional CA model for reducing the uncertainty of the distribution of simulated new urban patches. In this model, the growth pattern of urban patches is first estimated using a developed indicator that is based on the local variations in existing urban patches. The urban growth is then simulated by integrating the estimated growth pattern and land suitability using a pattern‐calibrated method. In this method, the pattern of new urban patches is gradually calibrated toward the dominant growth pattern through the steps of the CA model. The proposed model is applied to simulate urban growth in the Tehran megalopolitan area during 2000–2006–2012. The results from this model were compared with two common models: cell‐based CA and logistic‐patch CA. The proposed model yields a degree of patch‐level agreement that is 23.4 and 7.5% higher than those of these pre‐existing models, respectively. This reveals that the patch‐based CA model simulates actual development patterns much better than the two other models.
A multi‐objective framework for analysis of road network vulnerability for relief facility location during flood hazards: A case study of relief location analysis in Bankura District, India
Authors: Chakraborty Omprakash , Das Arup , Dasgupta Arindam , Mitra Pabitra , Ghosh Soumya K. , Mazumder Taraknath 
Published: January 2018

AbstractThe location of disaster management facilities is a challenging and multifaceted problem. The road networks, population distribution along the road networks, and disaster risk maps are the major components for management of this problem. This article aims to decide on the location of such facilities for flood hazards in a region. The methodology is based on a multi‐objective framework. Objective functions include edge importance indices under fair weather and elevation parameters of the edges. Multiple scenarios are simulated for varying levels of hazard, and the outputs are analyzed. Analyses are carried out for the individual percentage loss of road links. A case study has been presented for the Bankura District in West Bengal, India. The inferences drawn from the results identify the critical links over the road networks of the region. The study also indicates locations in the region for relief facility setups to enable best‐serving capabilities and provide safe shelters, even in the most adverse flood conditions. The article depicts the vulnerability status of the road networks of the region. Further, it identifies the locations for relief facility provisioning that bring out the best road utilization and the best‐serving capabilities within the flood‐affected area under different flood levels.
Elevated sympathetic vasomotor outflow in response to increased inspiratory muscle activity during exercise is less in young women compared with men
Authors: Katayama Keisho , Smith Joshua R. , Goto Kanako , Shimizu Kaori , Saito Mitsuru , Ishida Koji , Koike Teruhiko , Iwase Satoshi , Harms Craig A. 
Published: January 2018

New Findings
What is the central question of this study?
Premenopausal women have an attenuated inspiratory muscle metaboreflex‐induced increase in arterial blood pressure compared with men. It is unclear whether sympathetic vasomotor outflow during dynamic exercise with increased inspiratory muscle activation is less in young women than in men.

What is the main finding and its importance?
The magnitude of increased sympathetic vasomotor outflow during leg cycling with inspiratory resistance was smaller in women than in men. Less sympathetic vasomotor outflow with inspiratory muscle metaboreflex activation could be one of the mechanisms for the attenuated inspiratory muscle‐induced metaboreflex during exercise in young women.

AbstractWe compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age‐matched men. Eight women and seven men completed the study. The subjects performed two 10 min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and voluntary hyperventilation with or without inspiratory resistive breathing for 5 min (breathing frequency 50 breaths min−1 with a 50% duty cycle; inspiratory resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency was increased, accompanied by an increase in MAP in both men and women. Women, compared with men, had less of an increase in MAP (women +22.8 ± 12.3 mmHg versus men +32.2 ± 5.4 mmHg; P < 0.05) and MSNA burst frequency (women +9.6 ± 2.9 bursts min−1 versus men +14.6 ± 6.4 bursts min−1; P < 0.05). These results suggest that the attenuated inspiratory muscle‐induced metaboreflex during exercise in young women is attributable, in part, to a lesser sympathetic vasomotor outflow compared with men.
Ether‐à‐go‐go K+ channels: effective modulators of neuronal excitability
Authors: Bauer Christiane K. , Schwarz Jürgen R. 
Published: January 2018

AbstractMammalian ether‐à‐go‐go (EAG) channels are voltage‐gated K+ channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag‐related gene; Kv11) and elk (eag‐like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart, where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation. They can even support high frequency firing by preventing a depolarization‐induced Na+ channel block. EAG channels are modulated differentially, e.g. eag channels by intracellular Ca2+, erg channels by extracellular K+ and GPCRs, and elk channels by changes in pH. So far, only currents mediated by erg channels have been recorded in neurons with the help of selective blockers. Neuronal eag and elk currents have not been isolated due to the lack of suitable channel blockers. However, findings in KO mice indicate a physiological role of eag1 currents in synaptic transmission and an involvement of elk2 currents in cognitive performance. Human eag1 and eag2 gain‐of‐function mutations underlie syndromes associated with epileptic seizures.
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Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges
Authors: Wong Darren , Nielsen Travis B. , Bonomo Robert A. , Pantapalangkoor Paul , Luna Brian , Spellberg Brad 
Published: January 2018

SUMMARY

Acinetobacter
is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by
Acinetobacter
spp. are increasingly reported. Transmission of
Acinetobacter
and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by
Acinetobacter
spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for
Acinetobacter
spp. are desperately needed.
Cell Cycle Arrest and Apoptosis Induced by Porphyromonas gingivalis Require Jun N-Terminal Protein Kinase- and p53-Mediated p38 Activation in Human Trophoblasts
Authors: Inaba Hiroaki , Amano Atsuo , Lamont Richard J. , Murakami Yukitaka , Matsumoto-Nakano Michiyo 
Published: January 2018

ABSTRACT

Porphyromonas gingivalis
, a periodontal pathogen, has been implicated as a causative agent of preterm delivery of low-birth-weight infants. We previously reported that
P. gingivalis
activated cellular DNA damage signaling pathways and ERK1/2 that lead to G
1
arrest and apoptosis in extravillous trophoblast cells (HTR-8 cells) derived from the human placenta. In the present study, we further examined alternative signaling pathways mediating cellular damage caused by
P. gingivalis. P. gingivalis
infection of HTR-8 cells induced phosphorylation of p38 and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both G
1
arrest and apoptosis. In addition, heat shock protein 27 (HSP27) was phosphorylated through both p38 and JNK, and knockdown of HSP27 with small interfering RNA (siRNA) prevented both G
1
arrest and apoptosis. Furthermore, regulation of G
1
arrest and apoptosis was associated with p21 expression. HTR-8 cells infected with
P. gingivalis
exhibited upregulation of p21, which was regulated by p53 and HSP27. These results suggest that
P. gingivalis
induces G
1
arrest and apoptosis via novel molecular pathways that involve p38 and JNK with its downstream effectors in human trophoblasts.
Genome-Wide Identification by Transposon Insertion Sequencing of Escherichia coli K1 Genes Essential for
In Vitro
Growth, Gastrointestinal Colonizing Capacity, and Survival in Serum
Authors: McCarthy Alex J. , Stabler Richard A. , Taylor Peter W. 
Published: January 2018

ABSTRACT

Escherichia coli
K1 strains are major causative agents of invasive disease of newborn infants. The age dependency of infection can be reproduced in neonatal rats. Colonization of the small intestine following oral administration of K1 bacteria leads rapidly to invasion of the blood circulation; bacteria that avoid capture by the mesenteric lymphatic system and evade antibacterial mechanisms in the blood may disseminate to cause organ-specific infections such as meningitis. Some
E. coli
K1 surface constituents, in particular the polysialic acid capsule, are known to contribute to invasive potential, but a comprehensive picture of the factors that determine the fully virulent phenotype has not emerged so far. We constructed a library and constituent sublibraries of ∼775,000 Tn
5
transposon mutants of
E. coli
K1 strain A192PP and employed transposon-directed insertion site sequencing (TraDIS) to identify genes required for fitness for infection of 2-day-old rats. Transposon insertions were lacking in 357 genes following recovery on selective agar; these genes were considered essential for growth in nutrient-replete medium. Colonization of the midsection of the small intestine was facilitated by 167
E. coli
K1 gene products. Restricted bacterial translocation across epithelial barriers precluded TraDIS analysis of gut-to-blood and blood-to-brain transits; 97 genes were required for survival in human serum. This study revealed that a large number of bacterial genes, many of which were not previously associated with systemic
E. coli
K1 infection, are required to realize full invasive potential.

IMPORTANCE
Escherichia coli
K1 strains cause life-threatening infections in newborn infants. They are acquired from the mother at birth and colonize the small intestine, from where they invade the blood and central nervous system. It is difficult to obtain information from acutely ill patients that sheds light on physiological and bacterial factors determining invasive disease. Key aspects of naturally occurring age-dependent human infection can be reproduced in neonatal rats. Here, we employ transposon-directed insertion site sequencing to identify genes essential for the
in vitro
growth of
E. coli
K1 and genes that contribute to the colonization of susceptible rats. The presence of bottlenecks to invasion of the blood and cerebrospinal compartments precluded insertion site sequencing analysis, but we identified genes for survival in serum.
Gammaherpesvirus Colonization of the Spleen Requires Lytic Replication in B Cells
Authors: Lawler Clara , de Miranda Marta Pires , May Janet , Wyer Orry , Simas J. Pedro , Stevenson Philip G. 
Published: January 2018

ABSTRACT

Gammaherpesviruses infect lymphocytes and cause lymphocytic cancers. Murid herpesvirus-4 (MuHV-4), Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus all infect B cells. Latent infection can spread by B cell recirculation and proliferation, but whether this alone achieves systemic infection is unclear. To test the need of MuHV-4 for lytic infection in B cells, we flanked its essential ORF50 lytic transactivator with
loxP
sites and then infected mice expressing B cell-specific Cre (CD19-Cre). The floxed virus replicated normally in Cre
−
mice. In CD19-Cre mice, nasal and lymph node infections were maintained; but there was little splenomegaly, and splenic virus loads remained low. Cre-mediated removal of other essential lytic genes gave a similar phenotype. CD19-Cre spleen infection by intraperitoneal virus was also impaired. Therefore, MuHV-4 had to emerge lytically from B cells to colonize the spleen. An important role for B cell lytic infection in host colonization is consistent with the large CD8
+
T cell responses made to gammaherpesvirus lytic antigens during infectious mononucleosis and suggests that vaccine-induced immunity capable of suppressing B cell lytic infection might reduce long-term virus loads.

IMPORTANCE
Gammaherpesviruses cause B cell cancers. Most models of host colonization derive from cell cultures with continuous, virus-driven B cell proliferation. However, vaccines based on these models have worked poorly. To test whether proliferating B cells suffice for host colonization, we inactivated the capacity of MuHV-4, a gammaherpesvirus of mice, to reemerge from B cells. The modified virus was able to colonize a first wave of B cells in lymph nodes but spread poorly to B cells in secondary sites such as the spleen. Consequently, viral loads remained low. These results were consistent with virus-driven B cell proliferation exploiting normal host pathways and thus having to transfer lytically to new B cells for new proliferation. We conclude that viral lytic infection is a potential target to reduce B cell proliferation.
Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source
Authors: Zhang Jianbo , Sturla Shana , Lacroix Christophe , Schwab Clarissa 
Published: January 2018

ABSTRACT

Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrolein. Reuterin is an antimicrobial multicomponent system consisting of 3-hydroxypropionaldehyde, its dimer and hydrate, and also acrolein. The major conclusion is that gut microbes can metabolize glycerol to reuterin and that this transformation occurs
in vivo
. Given the known toxicity of acrolein, the observation that acrolein is formed in the gut necessitates further investigations on functional relevance for gut microbiota and the host.
Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic
Authors: Gagnon Alain , Acosta Enrique , Hallman Stacey , Bourbeau Robert , Dillon Lisa Y. , Ouellette Nadine , Earn David J. D. , Herring D. Ann , Inwood Kris , Madrenas Joaquin , Miller Matthew S. 
Published: January 2018

ABSTRACT
Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 “swine flu” pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 “Spanish flu.” Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 “swine flu” pandemic and during the resurgent 2013–2014 H1N1 outbreak for those born at the time of the 1957 H2N2 “Asian flu” pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.

IMPORTANCE
The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918—when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality. Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013–2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 “Asian flu” pandemic. These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect.
Examining patterns of multimorbidity, polypharmacy and risk of adverse drug reactions in chronic obstructive pulmonary disease: a cross-sectional UK Biobank study
Authors: Hanlon Peter , Nicholl Barbara I , Jani Bhautesh Dinesh , McQueenie Ross , Lee Duncan , Gallacher Katie I , Mair Frances S 
Published: January 2018

ObjectiveThis study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.DesignCross-sectional.SettingCommunity cohort.ParticipantsUK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).OutcomesMultimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without. Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.ResultsMultimorbidity was more common in participants with COPD than those without (17% vs 4%). Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury. Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.ConclusionsMultimorbidity is common in COPD and associated with high levels of polypharmacy. Co-prescription of drugs with various ADRs is common. Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs. Clinical guidelines should emphasise assessment of multimorbidity and ADR risk.