bluuebunny/crossref_metadata_2025 huggingface dataset:
Polls and Elections: Exploiting Donald Trump: Using Candidates' Positions to Assess Ideological Voting in the 2016 and 2008 Presidential Elections
Authors: Gooch Andrew , Huber Gregory A.
Published: April 2018

Testing theories of how candidate positions affect voting is often complicated by the strong correlation between candidate partisanship and candidate positions. We take advantage of Donald Trump's unusual candidacy to understand how candidates who depart from standard party positions affect perceptions of ideology and voting. We show in both 2016 and 2008 that respondents were more likely to report voting for the more ideologically proximate candidate, an advantage enjoyed by Trump in 2016 at much higher rates, in part because he was perceived as more moderate than prior candidates. What is most exceptional about Trump relative to previous candidates, however, is that voters were much less willing to place him anywhere in an ideological space. Being unwilling to place Trump was correlated with being much less likely to vote for him and suggests that some voters do not reward ambiguous or nonstandard issue positioning. More generally, we find evidence that in the contemporary era of strong partisan attachments, some voters still appear to decide which candidate to support, in part, on assessments of candidate ideology.
Coupling of respiration and attention via the locus coeruleus: Effects of meditation and pranayama
Authors: Melnychuk Michael Christopher , Dockree Paul M. , O'Connell Redmond G. , Murphy Peter R. , Balsters Joshua H. , Robertson Ian H.
Published: April 2018

The locus coeruleus (LC) has established functions in both attention and respiration. Good attentional performance requires optimal levels of tonic LC activity, and must be matched to task consistently. LC neurons are chemosensitive, causing respiratory phrenic nerve firing to increase frequency with higher CO2 levels, and as CO2 level varies with the phase of respiration, tonic LC activity should exhibit fluctuations at respiratory frequency. Top‐down modulation of tonic LC activity from brain areas involved in attentional regulation, intended to optimize LC firing to suit task requirements, may have respiratory consequences as well, as increases in LC activity influence phrenic nerve firing. We hypothesize that, due to the physiological and functional overlaps of attentional and respiratory functions of the LC, this small neuromodulatory nucleus is ideally situated to act as a mechanism of synchronization between respiratory and attentional systems, giving rise to a low‐amplitude oscillation that enables attentional flexibility, but may also contribute to unintended destabilization of attention. Meditative and pranayama practices result in attentional, emotional, and physiological enhancements that may be partially due to the LC's pivotal role as the nexus in this coupled system. We present original findings of synchronization between respiration and LC activity (via fMRI and pupil dilation) and provide evidence of a relationship between respiratory phase modulation and attentional performance. We also present a mathematical dynamical systems model of respiratory‐LC‐attentional coupling, review candidate neurophysiological mechanisms of changes in coupling dynamics, and discuss implications for attentional theory, meditation, and pranayama, and possible therapeutic applications.
Subtropical goats ovulate in response to the male effect after a prolonged treatment of artificial long days to stimulate their milk yield
Authors: Mendieta ES , Delgadillo JA , Flores JA , Flores MJ , Nandayapa E , Vélez LI , Zarazaga LA , Bedos M , Terrazas A , Hernández H
Published: April 2018

Contents

The objectives of this study were to determine (i) if in subtropical goats that gave birth during mid‐December, the exposition to an artificial long‐day photoperiod consisting in only 14 hr of light per day can increase the milk yield and (ii) to test whether these females can respond to the male effect at the end of the prolonged photoperiodic treatment. In experiment 1, 17 lactating goats were maintained under natural short days (control group), while another 22 goats were maintained under artificial long days (treated group) consisting in 14 hr light and 10 hr darkness starting at day 10 of lactation. The continuous exposition to an artificial long‐day photoperiod produced an increase in the milk yield level during the first 110 days of lactation (time × treatment interaction; p = .01), while none of the milk components were modified due to the photoperiodic treatment (p > .05). In experiment 2, all control and treated anovulatory goats were submitted to the male effect using photostimulated males. All females showed oestrous behaviour within the first 10 days that were in contact with males (100% in both groups; p > .05). Thus, the latency to onset of oestrus did not differ between females from control (58.2 ± 3.0 hr) and treated (62 ± 4.6 hr) groups. Male exposition provoked ovulation independently if females were previously under long days or natural photoperiod (96 vs 100%, respectively; p = .79). It was concluded that exposure to 14 hr of light per day in subtropical goats that gave birth in late autumn stimulates milk yield without preventing the ovulation in response to the male effect at the end of the prolonged photoperiodic treatment.
Evaluating The Use of Realtime Data in Forecasting Output Levels and Recessionary Events in the USA
Authors: Aristidou Chrystalleni , Lee Kevin , Shields Kalvinder
Published: April 2018

The paper proposes a modelling framework and evaluation procedure to judge the usefulness of realtime data sets incorporating past data vintages and survey expectations in forecasting. The analysis is based on ‘metamodels’ obtained by using model averaging techniques and judged by various statistical and economic criteria, including a novel criterion based on a fair bet. Analysing US output data over 1968, quarter 4–2015, quarter 1, we find that both elements of the realtime data are useful with their contributions varying over time. Revisions data are particularly valuable for point and density forecasts of growth but survey expectations are important in forecasting rare recessionary events.
Satisfaction with life in individuals with a lower limb amputation: The importance of active coping and acceptance
Authors: Pereira M. Graça , Ramos Cristiana , Lobarinhas Armanda , Machado J. Cunha , Pedras Susana
Published: April 2018

The aim of this study was to analyze the relationship between sociodemographic/clinical characteristics, coping strategies and satisfaction with life in individuals with lower limb amputation. Sixty‐three individuals with a lower limb amputation due to Diabetes and Peripheral Vascular Disease participated in the study and answered measures of coping strategies and satisfaction with life. Findings revealed high dissatisfaction with life. Acceptance and active coping were the most used coping strategies. Satisfaction with life was positively associated with active and planning coping, religion, acceptance and humour. There were differences in coping strategies according to gender, age, marital status, presence of residual limb pain, prosthesis use and mobility level. Results emphasize the differential role of coping strategies, for each individual. Psychosocial interventions need to take into consideration coping strategies during the process of rehabilitation and be specific regarding individuals` sociodemographic and clinical characteristics. This study may help design interventions that answer individuals with lower limb amputations given that coping strategies are a valuable resource in the promotion of satisfaction with life.
Estimation in monotone single‐index models
Authors: Groeneboom Piet , Hendrickx Kim
Published: April 2018

Single‐index models are popular regression models that are more flexible than linear models and still maintain more structure than purely nonparametric models. We consider the problem of estimating the regression parameters under a monotonicity constraint on the unknown link function. In contrast to the standard approach of using smoothing techniques, we review different “non‐smooth” estimators that avoid the difficult smoothing parameter selection. For about 30 years, one has had the conjecture that the profile least squares estimator is an
‐consistent estimator of the regression parameter, but the only non‐smooth argmin/argmax estimators that are actually known to achieve this
‐rate are not based on the nonparametric least squares estimator of the link function. However, solving a score equation corresponding to the least squares approach results in
‐consistent estimators. We illustrate the good behavior of the score approach via simulations. The connection with the binary choice and current status linear regression models is also discussed.
Massive transfusion: changing practice in a single Norwegian centre 2002–2015
Authors: Doughty H. , Apelseth T. O. , Sivertsen J. , Annaniasen K. , Hervig T.
Published: April 2018

Objectives

To describe the change in massive transfusion (MT) practice in a single Norwegian centre throughout the period 2002–2015.

Background

MT support for traumatic haemorrhage has changed since the mid‐2000s. However, life‐threatening haemorrhage may occur in other clinical specialties. In 2007, Haukeland University Hospital (HUS) introduced a universal MT programme including education, Acute Transfusion Packages (ATPs) and thromboelastography.

Methods/Materials

A retrospective review was performed of all MT episodes defined as ≥10 red cell concentrates (RCC) in 24 h. Episodes were identified using the laboratory information system. Patient records were reviewed manually for demographics, transfusion indication, haemostatic drugs and mortality. The ATPs contained six units RCC, six units Octaplas and two platelet concentrates (four buffy coats/apheresis in platelet additive solution (PAS)).

Results

A total of 410 episodes were identified in 410 patients. The mean patient age was 60 years (9–94), with a male predominance (64%); 87·1% of MT episodes were in support of surgery (cardiac services 42·7%; trauma 17·6%), and 29·8% of MTs involved platelet inhibitors, with 82·6% of these undergoing cardiac procedures. MT accounted for 2·8% of all RCCs and 3·4% of platelets issued. The mean ratio of blood components RCC: plasma: platelets changed from 1·0 : 0·37 : 0·39 in 2002–2006 (n = 149) to 1·0 : 0·79 : 0·85 in 2008–2015 (n = 241, P < 0·001). A sub‐analysis showed that cardiac specialities used proportionally more plasma and platelets.

Conclusion

The MT programme changed transfusion practice, resulting in greater use of plasma and platelets. MT was primarily used in major surgery. The practice in cardiac surgery may reflect changes in antiplatelet medication.
Effectiveness of viable cryopreserved placental membranes for management of diabetic foot ulcers in a real world setting
Authors: Raspovic Katherine M. , Wukich Dane K. , Naiman Daniel Q. , Lavery Lawrence A. , Kirsner Robert S. , Kim Paul J. , Steinberg John S. , Attinger Christopher E. , Danilkovitch Alla
Published: April 2018

In a multicenter randomized controlled trial (RCT), the use of viable cryopreserved placental membrane (vCPM) for chronic diabetic foot ulcers (DFUs) resulted in a higher proportion of wound closure in comparison to good wound care: 62% versus 21% (p < 0.01). However, patients in RCTs are not representative of daily physician practice. Healthcare databases serve as a valuable tool to evaluate therapy effectiveness and to supplement evidence from RCTs. The objective of this study was to evaluate the effectiveness of vCPM for DFU management using Net Health's WoundExpert® electronic health records (EHR). The primary endpoint was the proportion of DFUs that achieved complete closure. Other endpoints included time and number of grafts to closure, probability of wound closure by week 12, and the number of wound‐related infections and amputations. De‐identified EHR data for 360 patients with 441 wounds treated with vCPM were extracted from the database. Average patient age was 63.7 years with a mean wound size of 5.1 cm2 and an average wound duration of 102 days prior to vCPM treatment. For evaluation of clinical outcomes, 350 DFUs larger than 0.25 cm2 at baseline were analyzed. Closure at the end of treatment was achieved in 59.4% of wounds with a median treatment duration of 42.0 days and 4 applications of vCPM. The probability of wound closure at week 12 was 71%, and the number of amputations and wound‐related infections was 13 (3.0%) and 9 (2.0%), respectively. Data also demonstrated a correlation between wound size and closure rate as well as a correlation between > 50% wound area reduction by week 4 and wound closure by week 12. The results of this study mirror previous RCT efficacy data, supporting the benefits of vCPM for DFU management. These results can also influence policy and treatment decisions regarding advanced vCPM technology.
Nutrition Knowledge and Attitude Change of Students Studying in State and Private Secondary Schools
Authors: Kıvrak Ali Osman , Altın Mehmet
Published: April 2018

The aim of this study is to analyse the changes in nutrition knowledge and attitudes of secondary school students depending on certain socio-demographic factors. The universe of the study is composed of 521 students, including 142 female and 379 male students studying in the secondary school and the sampling group in Konya province private and state central secondary education schools. The "Nutrition Knowledge and Attitude Scale", developed by Ertürk (2010), was used for nutrition attitude and knowledge and personal information form to acquire socio-demographic information. Descriptive statistics of the data were made, variance and homogeneity were tested, independent sample t test was used for binary comparisons, One Way Anowa was utilized for multiple comparisons, and Tukey test was benefitted to determine difference sources. Nutrition knowledge of students in state schools was found to be lower than that of students in private schools and this gap was identified to be statistically significant (P <0.05). Nutritional knowledge and attitudes of female students were determined to be higher than males’ and this difference was found to be statistically significant (P <0.05). Nutritional knowledge and attitudes of students who received elective nutrition classes were found to be higher than those who did not have nutrition classes and this change was again found to be statistically significant (P <0.05). The number of siblings and education status of parents were found to be statistically significant variants (P <0.05). As a result, the high level of nutrition knowledge and attitudes of female students compared to male students, the status and role of cultural transfer and social structure featured on male and female can be seen as the reason for that matter. It can be said that taking a nutrition class has a positive influence on nutrition knowledge and attitude, and that private school students have more nutrition knowledge yet similar nutrition attitudes with those in state schools.
Opinions of Preservice Teachers on their Acceptance of the Use of Mobile Technologies For Teaching Purposes
Authors: Tonbuloğlu İsmail , Kıyıcı Mübin
Published: April 2018

The study examines opinions of preservice teachers on their acceptance of the use of mobile technologies for teaching purposes. This study is a phenomenological research. Semi-structured interviews were held with 4 preservice Turkish teachers and 4 preservice Science teachers selected by criterion sampling method. The resulting themes related to opinions of the preservice teachers on their acceptance of the use of mobile technologies for teaching purposes are as follows: “Perceived Usefulness and Ease of Use”, “Intention of Use and Attitude Towards Use”, “Social Effect”, “Individual Competencies”, “Integration in Educational Environment” and “Innovation”.
Knowledge and Use of Dietary Supplement Products by Deaf Athletes
Authors: Cengizhan Pelin Aksen
Published: April 2018

The purpose of this study was to determine the knowledge and use of dietary supplement products (DSP) among the deaf athletes of the Turkish Deaf Sports Federation. A total 74 voluntary athletes from various sports, 11 female and 63 male athletes (Mage=23.62±5.38 years) participated in this study. The data was collected through the survey method and was analyzed by Fischer Exact test, frequencies and percentage distribution. As a result, it has been determined that 39.2% of deaf athletes have knowledge about DSP and athlete diets; their rate of DSP use increases as their educational level increases; the rate of DSP use in national athletes is higher and that taekwondo athletes do not use DSP while a rate of at least 30.8% DSP use is evident in other branches. In addition, the findings show that the deaf athletes do not have sufficient knowledge about their DSP use and they have problems in accessing reliable information about this issue.
Effect of adding an insulator between metal and semiconductor layers on contact resistance
Authors: Kim Hyunjung , Jang Woochool , Lim Heewoo , Kweon Youngkyun , Bang Minwook , Kwon Saejin , Kim Bumsik , Cho Haewon , Jeon Hyeongtag
Published: April 2018

The authors investigated the effective Schottky barrier heights of metal and silicon contacts after insertion of insulator layers with different conduction band offsets. A decrease in Schottky barrier height after insertion of an insulator layer was observed. In particular, the Schottky barrier height of metal/semiconductor contacts was lowest when a ZnO layer was inserted compared to the other insulator layer types, because the conduction band offset between ZnO and silicon was the lowest among those measured. The authors also investigated current density as a function of the thickness of the insulator and doping concentration of silicon.
A computational flow-induced noise and time-reversal technique for analysing aeroacoustic sources
Authors: Croaker Paul , Mimani Akhilesh , Doolan Con , Kessissoglou Nicole
Published: April 2018

A simulation technique to analyse flow-induced noise problems that combines computational fluid dynamics (CFD), the boundary element method (BEM) and an aeroacoustic time-reversal (TR) source localisation method is presented. Hydrodynamic data are obtained from a high-fidelity CFD simulation of flow past a body and aeroacoustic sources are extracted based on Lighthill's acoustic analogy. The incident pressure field on the body due to the aeroacoustic sources is combined with a BEM representation of the body to obtain the spectrum of the direct, scattered and total acoustic pressure fields at far-field microphone locations. The microphone data are then used as input for the time-reversal simulations which are implemented by numerically solving two-dimensional linearized Euler equations. Decomposing the far-field pressure enables the TR simulation of the direct, scattered and total acoustic fields to be performed separately which yields the location and nature of the corresponding aeroacoustic sources. To demonstrate the hybrid CFD−BEM−TR technique, the sound generated by a cylinder in low Mach number cross-flow is considered. The nature of the aeroacoustic sources at the vortex shedding frequency and its second harmonic for the direct, scattered and total fields are identified.
Mass, height of burst, and source–receiver distance constraints on the acoustic coda phase delay method
Authors: Albert Sarah , Bowman Daniel , Rodgers Arthur , Seastrand Douglas
Published: April 2018

This research uses the acoustic coda phase delay method to estimate relative changes in air temperature between explosions with varying event masses and heights of burst. It also places a bound on source–receiver distance for the method. Previous studies used events with different shapes, height of bursts, and masses and recorded the acoustic codas at source–receiver distances less than 1 km. This research further explores the method using explosions that differ in mass (by up to an order of magnitude) and are placed at varying heights. Source–receiver distances also cover an area out to 7 km. Relative air temperature change estimates are compared to complementary meteorological observations. Results show that two explosions that differ by an order of magnitude cannot be used with this method because their propagation times in the near field and their fundamental frequencies are different. These differences are expressed as inaccuracies in the relative air temperature change estimates. An order of magnitude difference in mass is also shown to bias estimates higher. Small differences in height of burst do not affect the accuracy of the method. An upper bound of 1 km on source–receiver distance is provided based on the standard deviation characteristics of the estimates.
Glucan Binding Protein C of Streptococcus mutans Mediates both Sucrose-Independent and Sucrose-Dependent Adherence
Authors: Mieher Joshua L. , Larson Matthew R. , Schormann Norbert , Purushotham Sangeetha , Wu Ren , Rajashankar Kanagalaghatta R. , Wu Hui , Deivanayagam Champion
Published: April 2018

The high-resolution structure of glucan binding protein C (GbpC) at 1.14 Å, a sucrose-dependent virulence factor of the dental caries pathogen
Streptococcus mutans
, has been determined. GbpC shares not only structural similarities with the V regions of AgI/II and SspB but also functional adherence to salivary agglutinin (SAG) and its scavenger receptor cysteine-rich domains (SRCRs). This is not only a newly identified function for GbpC but also an additional fail-safe binding mechanism for
S. mutans
. Despite the structural similarities with
S. mutans
antigen I/II (AgI/II) and SspB of
Streptococcus gordonii
, GbpC remains unique among these surface proteins in its propensity to adhere to dextran/glucans. The complex crystal structure of GbpC with dextrose (β-
d
-glucose; Protein Data Bank ligand BGC) highlights exclusive structural features that facilitate this interaction with dextran. Targeted deletion mutant studies on GbpC's divergent loop region in the vicinity of a highly conserved calcium binding site confirm its role in biofilm formation. Finally, we present a model for adherence to dextran. The structure of GbpC highlights how artfully microbes have engineered the lectin-like folds to broaden their functional adherence repertoire.
Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease
Authors: Deng Liwen , Mu Rong , Weston Thomas A. , Spencer Brady L. , Liles Roxanne P. , Doran Kelly S.
Published: April 2018

Streptococcus agalactiae
(group B
Streptococcus
[GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the
ltdR
gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC)
in vitro
as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis
in vivo
. Correspondingly, infection of hCMEC with the Δ
ltdR
mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the Δ
ltdR
mutant was cleared more readily from the vaginal tract and also that infection with the Δ
ltdR
mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the Δ
ltdR
mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression.
Evidence that Clostridium perfringens Enterotoxin-Induced Intestinal Damage and Enterotoxemic Death in Mice Can Occur Independently of Intestinal Caspase-3 Activation
Authors: Freedman John C. , Navarro Mauricio A. , Morrell Eleonora , Beingesser Juliann , Shrestha Archana , McClane Bruce A. , Uzal Francisco A.
Published: April 2018

Clostridium perfringens
enterotoxin (CPE) is responsible for the gastrointestinal symptoms of
C. perfringens
type A food poisoning and some cases of nonfoodborne gastrointestinal diseases, such as antibiotic-associated diarrhea. In the presence of certain predisposing medical conditions, this toxin can also be absorbed from the intestines to cause enterotoxemic death. CPE action
in vivo
involves intestinal damage, which begins at the villus tips. The cause of this CPE-induced intestinal damage is unknown, but CPE can induce caspase-3-mediated apoptosis in cultured enterocyte-like Caco-2 cells. Therefore, the current study evaluated whether CPE activates caspase-3 in the intestines and, if so, whether this effect is required for the development of intestinal tissue damage or enterotoxemic lethality. Using a mouse ligated small intestinal loop model, CPE was shown to cause intestinal caspase-3 activation in a dose- and time-dependent manner. Most of this caspase-3 activation occurred in epithelial cells shed from villus tips. However, CPE-induced caspase-3 activation occurred after the onset of tissue damage. Furthermore, inhibition of intestinal caspase-3 activity did not affect the onset of intestinal tissue damage. Similarly, inhibition of intestinal caspase-3 activity did not reduce CPE-induced enterotoxemic lethality in these mice. Collectively, these results demonstrate that caspase-3 activation occurs in the CPE-treated intestine but that this effect is not necessary for the development of CPE-induced intestinal tissue damage or enterotoxemic lethality.
Forward Genetic Dissection of Biofilm Development by Fusobacterium nucleatum: Novel Functions of Cell Division Proteins FtsX and EnvC
Authors: Wu Chenggang , Al Mamun Abu Amar Mohamed , Luong Truc Thanh , Hu Bo , Gu Jianhua , Lee Ju Huck , D’Amore Melissa , Das Asis , Ton-That Hung
Published: April 2018

Fusobacterium nucleatum
is a key member of the human oral biofilm. It is also implicated in preterm birth and colorectal cancer. To facilitate basic studies of fusobacterial virulence, we describe here a versatile transposon mutagenesis procedure and a pilot screen for mutants defective in biofilm formation. Out of 10 independent biofilm-defective mutants isolated, the affected genes included the homologs of the
Escherichia coli
cell division proteins FtsX and EnvC, the electron transport protein RnfA, and four proteins with unknown functions. Next, a facile new gene deletion method demonstrated that nonpolar, in-frame deletion of
ftsX
or
envC
produces viable bacteria that are highly filamentous due to defective cell division. Transmission electron and cryo-electron microscopy revealed that the Δ
ftsX
and Δ
envC
mutant cells remain joined with apparent constriction, and scanning electron microscopy (EM) uncovered a smooth cell surface without the microfolds present in wild-type cells. FtsX and EnvC proteins interact with each other as well as a common set of interacting partners, many with unknown function. Last, biofilm development is altered when cell division is blocked by MinC overproduction; however, unlike the phenotypes of Δ
ftsX
and Δ
envC
mutants, a weakly adherent biofilm is formed, and the wild-type rugged cell surface is maintained. Therefore, FtsX and EnvC may perform novel functions in
Fusobacterium
cell biology. This is the first report of an unbiased approach to uncover genetic determinants of fusobacterial biofilm development. It points to an intriguing link among cytokinesis, cell surface dynamics, and biofilm formation, whose molecular underpinnings remain to be elucidated.

IMPORTANCE
Little is known about the virulence mechanisms and associated factors in
F. nucleatum
, due mainly to the lack of convenient genetic tools for this organism. We employed two efficient genetic strategies to identify
F. nucleatum
biofilm-defective mutants, revealing FtsX and EnvC among seven biofilm-associated factors. Electron microscopy established cell division defects of the Δ
ftsX
and Δ
envC
mutants, accompanied with a smooth cell surface, unlike the microfold, rugged appearance of wild-type bacteria. Proteomic studies demonstrated that FtsX and EnvC interact with each other as well as a set of common and unique interacting proteins, many with unknown functions. Importantly, blocking cell division by MinC overproduction led to formation of a weakly adherent biofilm, without alteration of the wild-type cell surface. Thus, this work links cell division and surface dynamics to biofilm development and lays a foundation for future genetic and biochemical investigations of basic cellular processes in this clinically significant pathogen.
Epigenetic Regulation of Tumor Suppressors byHelicobacter pyloriEnhances EBV-Induced Proliferation of Gastric Epithelial Cells
Authors: Pandey Saurabh , Jha Hem Chandra , Shukla Sanket Kumar , Shirley Meghan K. , Robertson Erle S.
Published: April 2018

Helicobacter pyloriand Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association withH. pyloriincreases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further,H. pylori-EBV coinfection causes chronic inflammation in pediatric patients. We have established anH. pylori-EBV coinfection model system using human gastric epithelial cells. We showed thatH. pyloriinfection can increase the oncogenic phenotype of EBV-infected cells and that the cytotoxin-associated gene (CagA) protein encoded byH. pyloristimulated EBV-mediated cell proliferation in this coinfection model system. This led to increased expression of DNA methyl transferases (DNMTs), which reprogrammed cellular transcriptional profiles, including those of tumor suppressor genes (TSGs), through hypermethylation. These findings provide new insights into a molecular mechanism whereby cooperativity between two oncogenic agents leads to enhanced oncogenic activity of gastric cancer cells.

IMPORTANCEWe have studied the cooperativity betweenH. pyloriand EBV, two known oncogenic agents. This led to an enhanced oncogenic phenotype in gastric epithelial cells. We now demonstrate that EBV-driven epigenetic modifications are enhanced in the presence ofH. pylori, more specifically, in the presence of its CagA secretory antigen. This results in increased proliferation of the infected gastric cells. Our findings now elucidate a molecular mechanism whereby expression of cellular DNA methyl transferases is induced influencing infection by EBV. Hypermethylation of the regulatory genomic regions of tumor suppressor genes results in their silencing. This drastically affects the expression of cell cycle, apoptosis, and DNA repair genes, which dysregulates their associated processes, and promotion of the oncogenic phenotype.
Human Cytomegalovirus Encodes a Novel FLT3 Receptor Ligand Necessary for Hematopoietic Cell Differentiation and Viral Reactivation
Authors: Crawford Lindsey B. , Kim Jung Heon , Collins-McMillen Donna , Lee Byeong-Jae , Landais Igor , Held Christine , Nelson Jay A. , Yurochko Andrew D. , Caposio Patrizia
Published: April 2018

The ability of human cytomegalovirus (HCMV) to reactivate from latent infection of hematopoietic progenitor cells (HPCs) is intimately linked to cellular differentiation. HCMV encodes UL7 that our group has shown is secreted from infected cells and induces angiogenesis. In this study, we show that UL7 is a ligand for Fms-like tyrosine kinase 3 receptor (Flt-3R), a well-known critical factor in HPC differentiation. We observed that UL7 directly binds Flt-3R and induces downstream signaling cascades, including phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways. Importantly, we show that UL7 protein induces differentiation of both CD34
+
HPCs and CD14
+
monocytes. Last, we show that an HCMV mutant lacking UL7 fails to reactivate in CD34
+
HPCs
in vitro
as well as in humanized mice. These observations define the first virally encoded differentiation factor with significant implications not only for HCMV reactivation but also for alteration of the hematopoietic compartment in transplant patients.

IMPORTANCE
Human cytomegalovirus (HCMV) remains a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients. CD34
+
hematopoietic progenitor cells (HPCs) represent a critical reservoir of latent HCMV in the transplant population, thereby providing a source of virus for dissemination to visceral organs. HCMV reactivation has been linked to HPC/myeloid cellular differentiation; however, the mechanisms involved in these events are poorly understood at the molecular level. In this study, we show that a viral protein is a ligand for Fms-like tyrosine kinase 3 receptor (Flt-3R) and that the binding of HCMV UL7 to the Flt-3R triggers HPC and monocyte differentiation. Moreover, the loss of UL7 prevents viral reactivation in HPCs
in vitro
as well as in humanized mice. These observations define the first virally encoded differentiation factor with significant implications not only for HCMV reactivation but also for alteration of the hematopoietic compartment in transplant patients.
Clinically Relevant Plasmid-Host Interactions Indicate that Transcriptional and Not Genomic Modifications Ameliorate Fitness Costs of
Klebsiella pneumoniae
Carbapenemase-Carrying Plasmids
Authors: Buckner Michelle M. C. , Saw Howard T. H. , Osagie Rachael N. , McNally Alan , Ricci Vito , Wand Matthew E. , Woodford Neil , Ivens Alasdair , Webber Mark A. , Piddock Laura J. V.
Published: April 2018

The rapid dissemination of antimicrobial resistance (AMR) around the globe is largely due to mobile genetic elements, such as plasmids. They confer resistance to critically important drugs, including extended-spectrum beta-lactams, carbapenems, and colistin. Large, complex resistance plasmids have evolved alongside their host bacteria. However, much of the research on plasmid-host evolution has focused on small, simple laboratory plasmids in laboratory-adapted bacterial hosts. These and other studies have documented mutations in both host and plasmid genes which occur after plasmid introduction to ameliorate fitness costs of plasmid carriage. We describe here the impact of two naturally occurring variants of a large AMR plasmid (pKpQIL) on a globally successful pathogen. In our study, after pKpQIL plasmid introduction, no changes in coding domain sequences were observed in their natural host,
Klebsiella pneumoniae
. However, significant changes in chromosomal and plasmid gene expression may have allowed the bacterium to adapt to the acquisition of the AMR plasmid. We hypothesize that this was sufficient to ameliorate the associated fitness costs of plasmid carriage, as pKpQIL plasmids were maintained without selection pressure. The dogma that removal of selection pressure (e.g., antimicrobial exposure) results in plasmid loss due to bacterial fitness costs is not true for all plasmid/host combinations. We also show that pKpQIL impacted the ability of
K. pneumoniae
to form a biofilm, an important aspect of virulence. This study used highly relevant models to study the interaction between AMR plasmids and pathogens and revealed striking differences from results of studies done on laboratory-adapted plasmids and strains.

IMPORTANCE
Antimicrobial resistance is a serious problem facing society. Many of the genes that confer resistance can be shared between bacteria through mobile genetic elements, such as plasmids. Our work shows that when two clinically relevant AMR plasmids enter their natural host bacteria, there are changes in gene expression, rather than changes to gene coding sequences. These changes in gene expression ameliorate the potential fitness costs of carriage of these AMR plasmids. In line with this, the plasmids were stable within their natural host and were not lost in the absence of selective pressure. We also show that better understanding of the impact of resistance plasmids on fundamental pathogen biology, including biofilm formation, is crucial for fighting drug-resistant infections.
Spacetime can be neither discrete nor continuous
Authors: Corda Christian
Published: April 2018

We show that our recent Bohr-like approach to black hole (BH) quantum physics implies that spacetime quantization could be energy-dependent. Thus, in a certain sense, spacetime can be neither discrete nor continuous. Our approach also permits to show that the “volume quantum” of the Schwarzschild spacetime increases with increasing energy during BH evaporation and arrives at a maximum value when the Planck scale is reached and the generalized uncertainty principle (GUP) prevents the total BH evaporation. Remarkably, this result does not depend on the BH original mass. The interesting consequence is that the behavior of BH evaporation should be the same for all Schwarzschild BHs when the Planck scale is approached.
A Universal Input, Single-Stage AC–DC LED Driver for an Auditorium Light
Authors: Agrawal Amit , Shrivastava Ashish , Jana Kartick C.
Published: April 2018

Analysis, design and simulation of 126[Formula: see text]W power supply with better power quality are presented in the proposed work to run an auditorium light emitting diode (LED) light operating at universal AC input mains (90–270[Formula: see text]V). A single-ended primary inductance converter (SEPIC) topology is designed and driven in continuous conduction mode (CCM) with advance feedback system to maintain constant voltage at output. A proportional integral (PI) controller is also proposed to make the system stable, and stability analysis is discussed in detail with the help of transfer function derived from the state space model. Bode, Nyquist and Polar plots are clearly drawn using the MATLAB tool to claim the system stability. For justification of mathematical analysis, a simulation of the proposed LED driver is also performed in MATLAB–Simulink using sim-power toolbox. The simulation results show the improved value of power quality indices like power factor (PF), total harmonic distortion (THD) and crest factor (CF) with constant rating of 84[Formula: see text]V, 1.5[Formula: see text]A at output. Improved PF and reduced THD are under the limit of international standards like IEC-61000-3-2 Class C requirement.
Call center service times are lognormal: A Fokker–Planck description
Authors: Gualandi Stefano , Toscani Giuseppe
Published: April 2018

Call centers are service networks in which agents provide telephone-based services. An important part of call center operations is represented by service durations. In recent statistical analysis of real data, it has been noted that the distribution of service times reveals a remarkable fit to the lognormal distribution. In this paper, we discuss a possible source of this behavior by resorting to classical methods of statistical mechanics of multi-agent systems. The microscopic service time variation leading to a linear kinetic equation with lognormal equilibrium density is built up introducing as main criterion for decision a suitable value function in the spirit of the prospect theory of Kahneman and Twersky.
Motion Planning with Energy Reduction for a Floating Robotic Platform Under Disturbances and Measurement Noise Using Reinforcement Learning
Authors: Tziortziotis Konstantinos , Tziortziotis Nikolaos , Vlachos Kostas , Blekas Konstantinos
Published: April 2018

This paper investigates the use of reinforcement learning for the navigation of an over-actuated, i.e. more control inputs than degrees of freedom, marine platform in unknown environment. The proposed approach uses an online least-squared policy iteration scheme for value function approximation in order to estimate optimal policy, in conjunction with a low-level control system that controls the magnitude of the linear velocity, and the orientation of the platform. Primary goal of the proposed scheme is the reduction of the consumed energy. To that end, we propose a variable reward function that depends on the energy consumption of the platform. We evaluate our approach in a complex and realistic simulation environment and report results concerning its performance on estimating optimal navigation policies under different environmental disturbances, and position GPS measurement noise. The proposed framework is compared, in terms of energy consumption, to a baseline approach based on virtual potential fields. The results show that the marine platform successfully discovers the target point following a sub-optimal path, maintaining reduced energy consumption.
Equilibrium statistical mechanics for self-gravitating systems of two species
Authors: He Ping
Published: April 2018

In this work, we attempt to generalize the statistical mechanics of self-gravitating systems to systems consisting of two species gravitating particles. Under the nondegenerate condition, with the second-order approximation, and with virialization relationships as additional constraints, we obtain the entropy expression for the two species system. Then, by extremizing the constrained entropy with variational calculus, we obtain a series of equations to describe the equilibrium states of the system. Under the assumption that there is no difference of velocity distributions between the two species, from the series of equilibrium-state equations, we obtain the relative ratio of the spatial distributions for the two species. The two species may be mixed homogeneously in space, yet with different choices of the relevant parameters [Formula: see text] and [Formula: see text], two Lagrangian multipliers in the statistical equilibrium equations, their spatial distributions may also differ from each other. The deviation of the spatial distributions between the two species is usually explained as mass segregation, which is confirmed by recent observations in some Galactic stellar clusters. We emphasis, however, that the mass segregation here is not caused by kinetic-energy exchange between the two species, but a new feature of our statistical approach, which is different from Lynden-Bell’s statistics. We believe that these results may have general significance to the statistical mechanics for the general long-range interaction systems.
Distributed Strain Damage Identification Technique for Long-Span Bridges Under Ambient Excitation
Authors: Xu Zhao-Dong , Li Shu , Zeng Xin
Published: April 2018

Distributed strain measurement, such as long-gauge fiber bragger grating (FBG) techniques, has developed rapidly in the field of structural health monitoring. However, strategies of corresponding damage identification still need to be enhanced. The damage identification technique based on distributed strain measurement is proposed identifying the structural damage under ambient excitation. Damage indices, like the distributed strain energy difference (DSED) and the relative distributed strain energy (RDSE), are derived from the power spectral density of the frequency response function of distributed strain response and further employed by detecting damages in the structure. A numerical analysis is performed on a long-span cable-stayed bridge with several assumed damage scenarios at various degrees in the girder. Damage localization capability and robustness of the proposed damage indices are discussed. In addition, damage quantification utilizing the proposed indices is conducted. The results indicate that the proposed technique can accurately identify the locations and extent of the damage under ambient vibration excitation.
Macromolecular crowding effects in flexible polymer solutions
Authors: Majumdar Bibhab Bandhu , Ebbinghaus Simon , Heyden Matthias
Published: April 2018

Biological environments are often “crowded” due to high concentrations (300–400[Formula: see text]g/L) of macromolecules. Computational modeling approaches like Molecular Dynamics (MD), rigid-body Brownian Dynamics and Monte Carlo simulations have recently emerged, which allow to study the effects macromolecular crowding at a microscopic level and to provide complementary information to experiments. Here, we use a recently introduced multiple-conformation Monte Carlo (mcMC) approach in order to study the influence of intermolecular interactions on the structural equilibrium of flexible polyethylene glycol (PEG) polymers under self-crowding conditions. The large conformational space accessible to PEG polymers allows us to evaluate the general applicability of the mcMC approach, which describes the intramolecular degrees of freedom by a finite-size ensemble of discrete conformations. Despite the simplicity of the approach, we show that influences of intermolecular interactions on the intramolecular free energy surface can be described qualitatively using mcMC. By varying the magnitude of distinct terms in the intermolecular potential, we can further study the compensating effects of repulsive and nonspecific attractive intermolecular interactions, which favor compact and extended polymer states, respectively. We use our simulation results to derive an analytical model that describes the effects of intermolecular interactions on the stability of PEG polymer conformations as a function of the radius of gyration and the corresponding solvent accessible surface. We use this model to confirm the role of molecular surfaces for attractive interactions that can counteract excluded volume effects. Extrapolation of the model further allows for the analysis of scenarios that are not easily accessible to direct simulations as described here.
Explicitly correlated orbital optimized contracted pair correlation methods: Foundations and applications
Authors: Lasar Christian , Klüner Thorsten
Published: April 2018

Pair correlation methods are able to achieve highly accurate solutions for chemical problems. Unfortunately, their applicability is generally restricted to medium-sized molecules due to storage requirements and computational costs. These restrictions can be partly overcome by local correlation methods. These methods use physical and mathematical criteria to decide which interactions are of such a long range that they do not have to be computed and saved. In our new ansatz, we define an alternative way towards local correlation. The range of interactions is strictly bound to the decay of integrals over Gaussian type geminals in the atomic orbital basis. The number of variables is reduced by orders of magnitude applying an efficient contraction scheme, leading to a naturally local representation of correlation effects. This scheme is extended by orbital optimization to describe multi-reference problems and explicit correlation to improve the basis set convergence.