bluuebunny/crossref_metadata_2025 huggingface dataset:
Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4) Perturbs the G
1
-S Cell Cycle Progression via Deregulation of the
cyclin D1
Gene
Authors: Lee Hye-Ra , Mitra Jaba , Lee Stacy , Gao Shou-Jiang , Oh Tae-Kwang , Kim Myung Hee , Ha Taekjip , Jung Jae U.
Published: October 2015

Kaposi's sarcoma-associated herpesvirus (KSHV) infection modulates the host cell cycle to create an environment optimal for its viral-DNA replication during the lytic life cycle. We report here that KSHV vIRF4 targets the β-catenin/CBP cofactor and blocks its occupancy on the
cyclin D1
promoter, suppressing the G
1
-S cell cycle progression and enhancing KSHV replication. This shows that KSHV vIRF4 suppresses host G
1
-S transition, possibly providing an intracellular milieu favorable for its replication.
A Unique Multibasic Proteolytic Cleavage Site and Three Mutations in the HA2 Domain Confer High Virulence of H7N1 Avian Influenza Virus in Chickens
Authors: Abdelwhab El-Sayed M. , Veits Jutta , Tauscher Kerstin , Ziller Mario , Teifke Jens P. , Stech Jürgen , Mettenleiter Thomas C.
Published: October 2015

In 1999, after circulation for a few months in poultry in Italy, low-pathogenic (LP) avian influenza (AI) H7N1 virus mutated into a highly pathogenic (HP) form by acquisition of a unique multibasic cleavage site (mCS), PEIPKGSRVRR*GLF (asterisk indicates the cleavage site), in the hemagglutinin (HA) and additional alterations with hitherto unknown biological function. To elucidate these virulence-determining alterations, recombinant H7N1 viruses carrying specific mutations in the HA of LPAI A/chicken/Italy/473/1999 virus (Lp) and HPAI A/chicken/Italy/445/1999 virus (Hp) were generated. Hp with a monobasic CS or carrying the HA of Lp induced only mild or no disease in chickens, thus resembling Lp. Conversely, Lp with the HA of Hp was as virulent and transmissible as Hp. While Lp with a multibasic cleavage site (Lp_CS445) was less virulent than Hp, full virulence was exhibited when HA2 was replaced by that of Hp. In HA2, three amino acid differences consistently detected between LP and HP H7N1 viruses were successively introduced into Lp_CS445. Q450L in the HA2 stem domain increased virulence and transmission but was detrimental to replication in cell culture, probably due to low-pH activation of HA. A436T and/or K536R restored viral replication
in vitro
and
in vivo
. Viruses possessing A436T and K536R were observed early in the HPAI outbreak but were later superseded by viruses carrying all three mutations. Together, besides the mCS, stepwise mutations in HA2 increased the fitness of the Italian H7N1 virus
in vivo
. The shift toward higher virulence in the field was most likely gradual with rapid optimization.

IMPORTANCE
In 1999, after 9 months of circulation of low-pathogenic (LP) avian influenza virus (AIV), a devastating highly pathogenic (HP) H7N1 AIV emerged in poultry, marking the largest epidemic of AIV reported in a Western country. The HPAIV possessed a unique multibasic cleavage site (mCS) complying with the minimum motif for HPAIV. The main finding in this report is the identification of three mutations in the HA2 domain that are required for replication and stability, as well as for virulence, transmission, and tropism of H7N1 in chickens. In addition to the mCS, Q450L was required for full virulence and transmissibility of the virus. Nonetheless, it was detrimental to virus replication and required A436T and/or K536R to restore replication, systemic spread, and stability. These results are important for better understanding of the evolution of highly pathogenic avian influenza viruses from low-pathogenic precursors.
Return to sport after open and microdiscectomy surgery versus conservative treatment for lumbar disc herniation: a systematic review with meta-analysis
Authors: Reiman Michael P , Sylvain Jonathan , Loudon Janice K , Goode Adam
Published: October 2015

Background

Lumbar disc herniation has a prevalence of up to 58% in the athletic population. Lumbar discectomy is a common surgical procedure to alleviate pain and disability in athletes. We systematically reviewed the current clinical evidence regarding athlete return to sport (RTS) following lumbar discectomy compared to conservative treatment.

Methods

A computer-assisted literature search of MEDLINE, CINAHL, Web of Science, PEDro, OVID and PubMed databases (from inception to August 2015) was utilised using keywords related to lumbar disc herniation and surgery. The design of this systematic review was developed using the guidelines of thePreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Methodological quality of individual studies was assessed using the Downs and Black scale (0–16 points).

Results

The search strategy revealed 14 articles. Downs and Black quality scores were generally low with no articles in this review earning a high-quality rating, only 5 articles earning a moderate quality rating and 9 of the 14 articles earning a low-quality rating. The pooled RTS for surgical intervention of all included studies was 81% (95% CI 76% to 86%) with significant heterogeneity (I2=63.4%, p<0.001) although pooled estimates report only 59% RTS at same level. Pooled analysis showed no difference in RTS rate between surgical (84% (95% CI 77% to 90%)) and conservative intervention (76% (95% CI 56% to 92%); p=0.33).

Conclusions

Studies comparing surgical versus conservative treatment found no significant difference between groups regarding RTS. Not all athletes that RTS return at the level of participation they performed at prior to surgery. Owing to the heterogeneity and low methodological quality of included studies, rates of RTS cannot be accurately determined.
Prevalence of diabetes and impaired fasting glucose in Peru: report from PERUDIAB, a national urban population-based longitudinal study
Authors: Seclen Segundo N , Rosas Moises E , Arias Arturo J , Huayta Ernesto , Medina Cecilia A
Published: October 2015

Objectives

We aimed to estimate the prevalences of diabetes and impaired fasting glucose (IFG) in a national sample in Peru and assess the relationships with selected sociodemographic variables.

Methods

We estimated prevalence in PERUDIAB study participants, a nationwide, stratified urban and suburban population selected by random cluster sampling. Between 2010 and 2012, questionnaires were completed and blood tests obtained from 1677 adults ≥25 years of age. Known diabetes was defined as participants having been told so by a doctor or nurse and/or receiving insulin or oral antidiabetic agents. Newly diagnosed diabetes was defined as fasting plasma glucose ≥126 mg/dL determined during the study and without a previous diabetes diagnosis. IFG was defined as fasting plasma glucose of 100–125 mg/dL.

Results

The estimated national prevalence of diabetes was 7.0% (95% CI 5.3% to 8.7%) and it was 8.4% (95% CI 5.6% to 11.3%) in metropolitan Lima. No gender differences were detected. Known and newly diagnosed diabetes prevalences were estimated as 4.2% and 2.8%, respectively. A logistic regression response surface model showed a complex trend for an increased prevalence of diabetes in middle-aged individuals and in those with no formal education. Diabetes prevalence was higher in coastal (8.2%) than in highlands (4.5%; p=0.03), and jungle (3.5%; p<0.02) regions. The estimated national prevalence of IFG was 22.4%, higher in males than in females (28.3% vs 19.1%; p<0.001), and higher in coastal (26.4%) than in highlands (17.4%; p=0.03), but not jungle regions (14.9%; p=0.07).

Conclusions

This study confirms diabetes as an important public health problem, especially for middle-aged individuals and those with no formal education. 40% of the affected individuals were undiagnosed. The elevated prevalence of IFG shows that nearly a quarter of the adult population of Peru has an increased risk of diabetes.
Improving validated depression screen among adolescent population in primary care practice using electronic health records (EHR).
Authors: Sudhanthar Sathyanarayan , Thakur Kripa , Sigal Yakov , Turner Jane
Published: October 2015

Adolescent depression, has been identified as one of the important risk factors for adolescent safety. The American Academy of Pediatrics (AAP) recommends screening the adolescent population for depression with a validated screening tool at least once a year. Given the time constraints in primary care, many physicians tend to rely more on clinical questioning to screen depression.This has the potential to miss many adolescents who may have mild to moderate depression which may prove detrimental to their emotional and physical health.

Quality measures had consistently indicated that the validated adolescent depression screening rate in our two pediatric clinics was 10-15% in the past two years starting from 2012. There was a need to increase our screening rate for adolescent depression with a validated questionnaire. The stakeholders identified were physicians, nurses and the health information team (HIT).

The Patient Health Questionnaire-2 (PHQ-2) is a standardized tool and serves as a good first step rapid screening of the population. A decision was made to implement the use of PHQ-2 to all the adolescents aged 11-21. A clinic flow protocol was developed. As the patient checks in, there will be a computer pop-up reminding nurses to administer the PHQ-2. The PHQ-2 self-scores in the Electronic Health Record (EHR) and if the score is three or more the nurses would automatically administer the PHQ-9 which is also embedded and self-scored in the EHR.

After 12 months of implementing this project with four PDSA cycles, the adolescent depression-screening rate improved from 10-15% from the previous two years to 65% (six month period) and 82% at the end of the 12 month period. The rate of referral to mental health services had also increased in the same time period compared to the previous years. In conclusion, screening for adolescent depression with a brief validated tool in a busy primary care office is possible with the help of the EHR.
Immunohistochemical detection of cytoplasmic nucleophosmin in formalin-fixed paraffin-embedded marrow trephine biopsies in acute myeloid leukaemia
Authors: Lit Benny Man Wai , Kwong Yok Lam , Wong Kit Fai
Published: October 2015

Aims

Nucleophosmin (NPM1) gene mutations resulting in cytoplasmic delocalisation of nucleophosmin (NPMc+) are the most common genetic abnormality in acute myeloid leukaemia (AML). In this study, we tested whether immunohistochemical (IHC) detection of cytoplasmic NPM1 (cNPM1) in formalin-fixed bone marrow trephine biopsies correlated withNPM1mutations and the prognostic impact ofNPM1and fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) gene mutations was also assessed.

Methods

A total of 71 Chinese adult de novo AML cases were evaluated for cNPM1 by IHC where the bone marrow trephines were fixed in 10% buffered formalin and decalcified by 5% EDTA.NPM1andFLT3-ITD gene mutations were also investigated using PCR, fragment analysis and direct DNA sequencing.

Results

IHC analysis of cNPM1 had a very good sensitivity (86.7%) and excellent specificity (96.4%) forNPM1mutation. The positive predictive value was 86.7% and the negative predictive value was 96.4%.NPM1mutations andFLT3-ITD were closely associated (p=0.003). Patients with mutatedNPM1and withoutFLT3-ITD mutation have a longer overall survival (p=0.042) than patients with bothNPM1andFLT3-ITD mutations.

Conclusions

Our results showed that IHC detection of cNPM1 in formalin-fixed trephine biopsies correlated well but not entirely withNPM1mutation. Furthermore,NPM1mutations were significantly more frequent inFLT3-ITD thanFLT3-wild-type cases.
Severe childhood obesity: an under-recognised and growing health problem
Authors: Bass Rosara , Eneli Ihuoma
Published: October 2015

Childhood obesity is a serious and urgent public health problem. In the last 10 years, there has been a concerted effort in the USA and globally to develop and implement educational, medical and public health interventions designed to attenuate its growth. The success of these efforts was probably responsible for the plateau in the prevalence rate of childhood obesity noted in the last two years. While the attenuation of the overall prevalence of childhood obesity is promising, data from the same cohort reveal a concerning upward trend in the number of children with severe obesity. The consequences of severe childhood obesity can be devastating. When compared to their moderately obese peers, children with severe obesity are at greater risk for adult obesity, early atherosclerosis, hypertension, type 2 diabetes, metabolic syndrome, fatty liver disease and premature death. The determinants for severe obesity include the same lifestyle, environmental, familial and societal risk factors reported for overweight or obesity. While all these risk factors must be screened for, genetic influences are distinct considerations that may have greater bearing especially with early-onset obesity. Treatments for severe childhood obesity include lifestyle intervention, specialised low-calorie diets and bariatric surgery. Outcomes of these treatments vary, with bariatric surgery clearly the most successful of the three for both short-term and long-term weight loss. Severe obesity in children and adolescents remains a challenging health condition. The enormous medical, emotional and financial burden these children and their families endure signals an urgent need to further investigate and standardise treatment modalities and improve outcomes.
The Nile perch invasion in Lake Victoria: cause or consequence of the haplochromine decline?
Authors: van Zwieten Paul A.M. , Kolding Jeppe , Plank Michael J. , Hecky Robert E. , Bridgeman Thomas B. , MacIntyre Sally , Seehausen Ole , Silsbe Greg M.
Published: October 2015

We review alternative hypotheses and associated mechanisms to explain Lake Victoria’s Nile perch (Lates niloticus) takeover and concurrent reduction in haplochromines through a (re)analysis of long-term climate, limnological, and stock observations in comparison with size-spectrum model predictions of co-existence, extinction, and demographic change. The empirical observations are in agreement with the outcomes of the model containing two interacting species with life histories matching Nile perch and a generalized haplochromine. The dynamic interactions may have depended on size-related differences in early juvenile mortality: mouth-brooding haplochromines escape predation mortality in early life stages, unlike Nile perch, which have miniscule planktonic eggs and larvae. In our model, predation on the latter by planktivorous haplochromine fry acts as a stabilizing factor for co-existence, but external mortality on the haplochromines would disrupt this balance in favor of Nile perch. To explain the observed switch, mortality on haplochromines would need to be much higher than the fishing mortality that can be realistically reconstructed from observations. Abrupt concomitant changes in algal and zooplankton composition, decreased water column transparency, and widespread hypoxia from increased eutrophication most likely caused haplochromine biomass decline. We hypothesize that the shift to Nile perch was a consequence of an externally caused, climate-triggered decrease in haplochromine biomass and associated recruitment failure rather than a direct cause of the introduction.
Energy Harvesting Leveraging Piezoelectric Property of ZnO Nanorods
Authors: Rivera Abdiel , Mazady Anas , Anwar Mehdi
Published: October 2015

Vertical ZnO nanorods (NRs) were grown on flexible plastic substrates at low temperature using hydrothermal synthesis method. An energy scavenging piezoelectric device was constructed using two flexible substrates with the NR sides facing each other providing a maximum open-circuit voltage of 1.4 V (peak). Two sets of three piezoelectric devices connected in series in a half-diode-bridge circuit configuration was demonstrated to turn on a commercial red LED.
Multi-Bit Quantum Dot Nonvolatile Memory (QDNVM) Using Cladded Germanium and Silicon Quantum Dots
Authors: Lingalugari Murali , Chan Pik-Yiu , Heller Evan , Jain Faquir
Published: October 2015

In this paper, we are experimentally demonstrating the multi-bit storage of a nonvolatile memory device with cladded quantum dots as the floating gate. These quantum dot nonvolatile memory (QDNVM) devices were fabricated by using standard complementary metal-oxide-semiconductor (CMOS) process. The quantum dots in the floating gate region assembled using site-specific selfassembly (SSA) technique. Quantum mechanical simulations of this device structure are also presented. The experimental results show that the voltage separation between the bits was 0.15V and the voltage pulses required to write these bits were 11.7V and 30V. These devices demonstrated the larger write voltage separation between the bits.
Minimax modules, local homology and local cohomology
Authors: Nam Tran Tuan
Published: October 2015

We show some results about local homology modules and local cohomology modules concerning Grothendieck’s conjecture and Huneke’s question. We also show some equivalent properties of [Formula: see text]-separated modules and of minimax local homology modules. By duality, we get some properties of Grothendieck’s local cohomology modules.
The vertex operator for a generalization of MacMahon’s formula
Authors: Cai Liqiang , Wang Lifang , Wu Ke , Yang Jie
Published: October 2015

We provide a vertex operator realization for a two-parameter generalization of MacMahon’s formula introduced by M. Vuletić [Trans. Amer. Math. Soc. 361, 2789 (2009)]. Since the generalized MacMahon function is the kernel function of some Macdonald symmetric function, we consider the action of two vertex operators on a state corresponding to a Macdonald symmetric function. It becomes evident that the vertex operators appear to be the creation and annihilation operators, respectively on the state.
A quasi-exactly solvable model: Two charges in a magnetic field subject to a non-Coulomb mutual interaction
Authors: Kreshchuk Michael
Published: October 2015

In this paper, we extend the class of QM problems which permit for quasi-exact solutions. Specifically, we consider planar motion of two interacting charges in a constant uniform magnetic field. While Turbiner and Escobar–Ruiz (2013) addressed the case of the Coulomb interaction between the particles, we explore three other potentials. We do this by reducing the appropriate Hamiltonians to the second-order polynomials in the generators of the representation of SL(2, C) group in the differential form. This allows us to perform partial diagonalization of the Hamiltonian and to reduce the search for the first few energies and the corresponding wavefunctions to an algebraic procedure.
Novel three chiral azobenzene polyurethanes: Preparation, optical properties and simulation comparisons of two different polymeric thermo-optic switches
Authors: Chen Caihong , Yang Zhening , Qiu Fengxian , Ye Feiyan , Cao Guorong , Guan Yijun , Yang Dongya
Published: October 2015

Three different structures of chiral side-chain azobenzene polyurethane (CAPU-1), chiral graft azobenzene polyurethane (CAPU-2) and chiral bisazo polyurethane (CAPU-3) were prepared by diazo coupling reaction. The structures, thermal, mechanical properties, refractive index (n) and transmission loss of CAPU-1~3 were investigated. The Y-branch and Mach–Zehnder polymeric thermo-optic switches were simulated based on the synthesized three chiral azo polyurethanes as waveguide materials. The response time differences are owing to the different substituents and structure of the azo compound. The conclusion had potential significance to improve and develop the new digital optical and thermo-optic switch (TOS) with short response time and low driving power.
Study of modulation instability for nonlinear Schrödinger equation phase locked with an external source
Authors: Sharma Vivek Kumar , Goyal Amit , Goswamy J.
Published: October 2015

We study the modulation instability (MI) for nonlinear Schrödinger equation phase locked to an external source. We analytically compute the growth rate and analyze the possibility of existence of MI for self-focusing and self-defocusing nonlinearities for positive and negative values of the homogeneous source term coefficient. We further investigate the impact of variation of nonlinear coefficient and variation of source term coefficient on the existence of MI. Phase-locking is the key characteristic that enables us to conduct analytical investigations of MI in this dynamical system, that appertains to pulse propagation through asymmetric twin-core fibers.
Delayed-dynamical optical bistability within and without the rotating wave approximation
Authors: Lynch S. , Alharbey R. A. , Batarfi H. A. , Hassan S. S.
Published: October 2015

Optical bistability (OB) for a homogeneously broadened two-level atomic system in a ring cavity is investigated within and without the rotating wave approximation (RWA) using nonautonomous Maxwell–Bloch equations subject to a time delay. It is shown that the dynamics both within and without the RWA are susceptible to the introduction of time delays in the differential equations. A range of instability scenarios are found as certain parameters are ramped up and down and these can affect the bistable operation of the physical devices. However, the introduction of a time delay can also result in an important positive application; for the first time, as far as the authors are aware, it is shown that a type of butterfly hysteresis can occur in the fundamental component, which is a relatively strong output signal, and may be desired in optical signal processing.
GLOBAL OPTIMIZATION METHOD APPLIED TO THE KINEMATICS OF GAIT IN PREGNANT WOMEN
Authors: AGUIAR LILIANA , ANDRADE CARLOS , BRANCO MARCO , SANTOS-ROCHA RITA , VIEIRA FILOMENA , VELOSO ANTÓNIO
Published: October 2015

Morphological changes are associated to pregnancy, such as weight gain and increased volume of the trunk. The soft tissue artifact can also increase with these characteristics and affect the real joint kinematics. The main objective of this study was to understand the effect of using three different constraining sets in the lower limb joints, in the amount of soft tissue artifact (STA) of pregnant women, in order to obtain the most appropriated joint set to be used in gait and in this population. The ankle, knee and hip joints were modeled respectively with the following characteristics: (1) Universal–revolute–spherical (URS), (2) spherical–revolute–spherical (SRS) and (3) spherical–spherical–spherical (SSS). The six degrees of freedom (6DOF) model was used as the basis for comparison and considered the one with the highest error associated to the STA. In pregnant women, the URS model seems to affect more the kinematic variables when compared with the 6DOF model. Assuming that the kinematic error associated with pregnant women is increased due to the STA, the URS model may be affecting more the angular kinematics of the knee joint. SSS model seems to be more appropriated to analyze gait in second trimester pregnant women.
Emotion Recognition During Speech Using Dynamics of Multiple Regions of the Face
Authors: Kim Yelin , Provost Emily Mower
Published: October 2015

The need for human-centered, affective multimedia interfaces has motivated research in automatic emotion recognition. In this article, we focus on facial emotion recognition. Specifically, we target a domain in which speakers produce emotional facial expressions while speaking. The main challenge of this domain is the presence of modulations due to both emotion and speech. For example, an individual's mouth movement may be similar when he smiles and when he pronounces the phoneme /IY/, as in “cheese”. The result of this confusion is a decrease in performance of facial emotion recognition systems. In our previous work, we investigated the joint effects of emotion and speech on facial movement. We found that it is critical to employ proper temporal segmentation and to leverage knowledge of spoken content to improve classification performance. In the current work, we investigate the temporal characteristics of specific regions of the face, such as the forehead, eyebrow, cheek, and mouth. We present methodology that uses the temporal patterns of specific regions of the face in the context of a facial emotion recognition system. We test our proposed approaches on two emotion datasets, the IEMOCAP and SAVEE datasets. Our results demonstrate that the combination of emotion recognition systems based on different facial regions improves overall accuracy compared to systems that do not leverage different characteristics of individual regions.
Enabling Context-Aware Indoor Augmented Reality via Smartphone Sensing and Vision Tracking
Authors: Liu Kaikai , Li Xiaolin
Published: October 2015

Augmented reality (AR) aims to render the world that users see and overlay information that reflects the real physical dynamics. The digital view could be potentially projected near the Point-of-Interest (POI) in a way that makes the virtual view attached to the POI even when the camera moves. Achieving smooth support for movements is a subject of extensive studies. One of the key problems is where the augmented information should be added to the field of vision in real time. Existing solutions either leverage GPS location for rendering outdoor AR views (hundreds of kilometers away) or rely on image markers for small-scale presentation (only for the marker region). To realize AR applications under various scales and dynamics, we propose a suite of algorithms for fine-grained AR view tracking to improve the accuracy of attitude and displacement estimation, reduce the drift, eliminate the marker, and lower the computation cost. Instead of requiring extremely high, accurate, absolute locations, we propose multimodal solutions according to mobility levels without additional hardware requirement. Experimental results demonstrate significantly less error in projecting and tracking the AR view. These results are expected to make users excited to explore their surroundings with enriched content.
Uncertain Graph Processing through Representative Instances
Authors: Parchas Panos , Gullo Francesco , Papadias Dimitris , Bonchi Francesco
Published: October 2015

Data in several applications can be represented as an uncertain graph whose edges are labeled with a probability of existence. Exact query processing on uncertain graphs is prohibitive for most applications, as it involves evaluation over an exponential number of instantiations. Thus, typical approaches employ Monte-Carlo sampling, which (i) draws a number of possible graphs (samples), (ii) evaluates the query on each of them, and (iii) aggregates the individual answers to generate the final result. However, this approach can also be extremely time consuming for large uncertain graphs commonly found in practice. To facilitate efficiency, we study the problem of extracting a single
representative
instance from an uncertain graph. Conventional processing techniques can then be applied on this representative to closely approximate the result on the original graph.

In order to maintain data utility, the representative instance should preserve structural characteristics of the uncertain graph. We start with representatives that capture the expected vertex degrees, as this is a fundamental property of the graph topology. We then generalize the notion of vertex degree to the concept of
n
-clique cardinality, that is, the number of cliques of size
n
that contain a vertex. For the first problem, we propose two methods: Average Degree Rewiring (ADR), which is based on random edge rewiring, and Approximate B-Matching (ABM), which applies graph matching techniques. For the second problem, we develop a greedy approach and a game-theoretic framework. We experimentally demonstrate, with real uncertain graphs, that indeed the representative instances can be used to answer, efficiently and accurately, queries based on several metrics such as shortest path distance, clustering coefficient, and betweenness centrality.
How men can help women in CS; winning 'computing's Nobel prize'
Authors: Barr Valerie , Stonebraker Michael
Published: October 2015

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Valerie Barr suggests how men can better promote women in computing, while Michael Stonebraker shares how it feels to receive the top honor in the computer science field.
Mechanisms of Bacterial Colonization of the Respiratory Tract
Authors: Siegel Steven J. , Weiser Jeffrey N.
Published: October 2015

Respiratory tract infections are an important cause of morbidity and mortality worldwide. Chief among these are infections involving the lower airways. The opportunistic bacterial pathogens responsible for most cases of pneumonia can cause a range of local and invasive infections. However, bacterial colonization (or carriage) in the upper airway is the prerequisite of all these infections. Successful colonizers must attach to the epithelial lining, grow on the nutrient-limited mucosal surface, evade the host immune response, and transmit to a susceptible host. Here, we review the molecular mechanisms underlying these conserved stages of carriage. We also examine how the demands of colonization influence progression to disease. A range of bacteria can colonize the upper airway; nevertheless, we focus on strategies shared by many respiratory tract opportunistic pathogens. Understanding colonization opens a window to the evolutionary pressures these pathogens face within their animal hosts and that have selected for attributes that contribute to virulence and pathogenesis.
Molecular Pathogenesis ofEhrlichia chaffeensisInfection
Authors: Rikihisa Yasuko
Published: October 2015

Ehrlichia chaffeensis is an obligatory intracellular and cholesterol-dependent bacterium that has evolved special proteins and functions to proliferate inside leukocytes and cause disease. E. chaffeensis has a multigene family of major outer membrane proteins with porin activity and induces infectious entry using its entry-triggering protein to bind the human cell surface protein DNase X. During intracellular replication, three functional pairs of two-component systems are sequentially expressed to regulate metabolism, aggregation, and the development of stress-resistance traits for transmission. A type IV secretion effector of E. chaffeensis blocks mitochondrion-mediated host cell apoptosis. Several type I secretion proteins are secreted at the Ehrlichia–host interface. E. chaffeensis strains induce strikingly variable inflammation in mice. The central role of MyD88, but not Toll-like receptors, suggests that Ehrlichia species have unique inflammatory molecules. A recent report about transient targeted mutagenesis and random transposon mutagenesis suggests that stable targeted knockouts may become feasible in Ehrlichia.
Circadian variation of variability and irregularity of heart rate in patients with permanent atrial fibrillation: relation to symptoms and rate control drugs
Authors: Corino Valentina D. A. , Platonov Pyotr G. , Enger Steve , Tveit Arnljot , Ulimoen Sara R.
Published: October 2015

The aim of the present study was to evaluate diurnal variations of the variability and irregularity of heart rate (HR) in patients with permanent atrial fibrillation (AF) with and without rate control drugs. Thirty-eight patients with permanent AF were part of an investigator-blind crossover study comparing diltiazem, verapamil, metoprolol, and carvedilol. We analyzed five Holter recordings per patient: at baseline (no rate control drug) and with each of the four drug regimens. HR, variability (SD; percentages of interval differences of successive RR intervals of >20, 50, and 80 ms; and root of the mean squared differences of successive RR intervals), and irregularity (approximate and sample entropy) parameters were computed in 20-min long nonoverlapping segments. Circadian rhythmicity was evaluated using cosinor analysis to each parameter series, which is characterized by the 24-h mean [midline statistic of rhythm (MESOR)] and excursion over the mean (amplitude). Arrhythmia-related symptoms were assessed by a questionnaire measuring symptom severity and frequency. HR and variability parameters showed a significant circadian variation in most patients, whereas only a small minority of the patients had circadian variations of irregularity parameters. Patients with circadian approximate entropy n at baseline had more severe symptoms (symptom severity: 9 ± 4 vs. 6 ± 5, P < 0.05, circadian vs. noncircadian variations). All drugs decreased the MESOR of HR and increased the MESOR of variability parameters. Only carvedilol and metoprolol decreased the normalized amplitude over 24 h of all parameters and HR. In conclusion, HR and RR variability parameters present a circadian variation in patients with permanent AF, whereas few patients demonstrated circadian fluctuations in irregularity parameters, suggesting different physiological mechanisms.
Almost Periodic Solution of a Discrete Commensalism System
Authors: Xue Yalong , Xie Xiangdong , Chen Fengde , Han Rongyu
Published: October 2015

A nonautonomous discrete two-species Lotka-Volterra commensalism system with delays is considered in this paper. Based on the discrete comparison theorem, the permanence of the system is obtained. Then, by constructing a new discrete Lyapunov functional, a set of sufficient conditions which guarantee the system global attractivity are obtained. If the coefficients are almost periodic, there exists an almost periodic solution and the almost periodic solution is globally attractive.
Protective Effect ofCalculus Bovis Sativuson Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice
Authors: Li Xiping , Xu Yanjiao , Zhang Chengliang , Deng Li , Chang Mujun , Yu Zaoqin , Liu Dong
Published: October 2015

Calculus Bovis Sativus(CBS) is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS-) induced ulcerative colitis (UC) in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI), colon length, colonic myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α(TNF-α), interleukin- (IL-) 1βand IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities.
Climate Change and Sugarcane Production: Potential Impact and Mitigation Strategies
Authors: Zhao Duli , Li Yang-Rui
Published: October 2015

Sugarcane (Saccharum officinarumL.) is an important crop for sugar and bioenergy worldwide. The increasing greenhouse gas emission and global warming during climate change result in the increased frequency and intensity of extreme weather events. Climate change is expected to have important consequences for sugarcane production in the world, especially in the developing countries because of relatively low adaptive capacity, high vulnerability to natural hazards, and poor forecasting systems and mitigating strategies. Sugarcane production may have been negatively affected and will continue to be considerably affected by increases in the frequency and intensity of extreme environmental conditions due to climate change. The degree of climate change impact on sugarcane is associated with geographic location and adaptive capacity. In this paper, we briefly reviewed sugarcane response to climate change events, sugarcane production in several different countries, and challenges for sugarcane production in climate change in order for us to better understand effects of climate change on sugarcane production and to propose strategies for mitigating the negative impacts of climate change and improving sugarcane production sustainability and profitability.
Clinicopathologic and Prognostic Value of Serum Carbohydrate Antigen 19-9 in Gastric Cancer: A Meta-Analysis
Authors: Song Yong-xi , Huang Xuan-zhang , Gao Peng , Sun Jing-xu , Chen Xiao-wan , Yang Yu-chong , Zhang Cong , Liu Hong-peng , Wang Hong-chi , Wang Zhen-ning
Published: October 2015

Background.The clinical value of carbohydrate antigen (CA) 19-9 in gastric cancer is controversial. We evaluated the clinicopathologic and prognostic value of CA 19-9 in gastric cancer.Methods.A literature search was conducted in PubMed and Embase databases. Odds ratios (ORs), risk ratios (RR), hazard ratios (HRs), and 95% confidence intervals (CIs) were used as effect measures.Results. Thirty-eight studies were included. Results showed that there were significant differences in the incidence of high CA 19-9 levels between stages III/IV and I/II groups (OR = 3.36; 95% CI = 2.34–4.84), the pT3/T4 and pT1/T2 groups (OR = 2.40; 95% CI = 1.60–3.59), the lymph node-positive and node-negative groups (OR = 2.91; 95% CI = 2.21–3.84), the metastasis-positive and metastasis-negative groups (OR = 2.76; 95% CI = 1.12–6.82), and vessel invasion-positive and invasion-negative groups (OR = 1.66; 95% CI = 1.11–2.48). Moreover, CA 19-9 was significantly associated with poor overall survival (HR = 1.83; 95% CI = 1.56–2.15), disease-free survival (HR = 1.85; 95% CI = 1.16–2.95), and disease-specific survival (HR = 1.33; 95% CI = 1.10–1.60) in gastric cancer.Conclusions. Our meta-analysis showed that CA 19-9 indicates clinicopathologic characteristics of gastric cancer and is associated with a poor prognosis.
Tunable Plasmon Resonance in Ag‐Au Split‐Ring Resonator with Inner Metallic Cross Heterogeneous Dimer Array
Authors: Zhou Xin , Wen Shuangchun , Tang Bin , Yang Diwu , He Jun
Published: October 2015

The plasmon resonance behavior in Ag‐Au split‐ring resonator (SRR) heterogeneous dimer array has been investigated numerically by using the finite difference time domain (FDTD) method. The resonance dips were tuned with the metallic SRR dimer arrays constituted by different metals. For the Ag‐Au heterogeneous SRRs dimer array, with the arms of metallic cross lengths increasing, the resonance dips in the visible region red shifted but the locations of resonance modes in the near‐infrared region kept immovability. On the contrary, the locations of resonance dips in the visible region kept immovability but the resonance modes in the near‐infrared region red shifted obviously with the air cuts widths decreasing. The whole resonance dips exhibited a red‐shift as the environmental dielectric constants increase. The electric and magnetic field distributions of certain resonance wavelengths were also investigated.
Research on Improved Adaptive Control for Static Synchronous Compensator in Power System
Authors: Zhang Chao , Zhang Aimin , Zhang Hang , Geng Yingsan , Bai Yunfei
Published: October 2015

This paper deals with the problems of “explosion of term,” uncertain parameter in static synchronous compensator (STATCOM) system with nonlinear time-delay. An improved adaptive controller is proposed to enhance the transient stability of system states and reduce computational complexity of STATCOM control system. In contrast to backstepping control scheme in high order systems, the problem of “explosion of term” is avoided by designing dynamic surface controller. The low pass filter is included to allow a design where the model is not differentiated and thus has prevented the mathematical complexities effectively. In addition, unlike the traditional adaptive control schemes, the certainty equivalence principle is not required for estimating the uncertain parameter by system immersion and manifold invariant (I&I) adaptive control. A smooth function is added to ensure that the estimation error converges to zero in finite time. The effectiveness of the proposed controller is verified by the simulations. Compared with adaptive backstepping and proportion integration differentiation (PID), the oscillation amplitudes of transient response are reduced by nearly half, and the time of reaching steady state is shortened by at least 11%.
Repeated Game for Distributed Estimation in Autonomous Clustered Wireless Sensor Networks
Authors: Liu Guiyun , Liu Yonggui , Yao Jing , Chen Hongbin , Tang Dong
Published: October 2015

A commonly encountered problem in wireless sensor networks (WSNs) applications is to reconstruct the state of nature, that is, distributed estimation of a parameter of interest through WSNs’ observations. However, the distributed estimation in autonomous clustered WSNs faces a vital problem of sensors’ selfishness. Each sensor autonomously decides whether or not to transmit its observations to the fusion center (FC) and not be controlled by the fusion center (FC) any more. Thus, to encourage cooperation within selfish sensors, infinitely and finitely repeated games are firstly modeled to depict sensors’ behaviors. Then, the existences of Nash equilibriums for infinitely and finitely repeated games are discussed. Finally, simulation results show that the proposed Nash equilibrium strategies are effective.
Analysis of mTOR Gene Aberrations in Melanoma Patients and Evaluation of Their Sensitivity to PI3K–AKT–mTOR Pathway Inhibitors
Authors: Kong Yan , Si Lu , Li Yiqian , Wu Xiaowen , Xu Xiaowei , Dai Jie , Tang Huan , Ma Meng , Chi Zhihong , Sheng Xinan , Cui Chuanliang , Guo Jun
Published: October 2015

Purpose: mTOR is a validated target in cancer. It remains to be determined whether melanoma patients bearing mTOR mutation could be selected for treatment with PI3K–AKT–mTOR pathway inhibitors.

Experimental Design: A total of 412 melanoma samples were included. Gene aberrations in all exons of mTOR were detected by Sanger sequencing and confirmed by using Agilent's SureSelect Target Enrichment System. HEK293T cells stably expressing mTOR mutants were constructed by using transcription activator-like effector nucleases technique. Function of mTOR mutants and in vitro sensitivity of gain-of-function mTOR mutations to PI3K–AKT–mTOR pathway inhibitors were analyzed.

Results: The overall incidence of somatic nonsynonymous mutations of mTOR was 10.4% (43/412). mTOR nonsynonymous mutations were relatively more frequent in acral (11.0%) and mucosal (14.3%) melanomas than in chronic sun-induced damage (CSD; 6.7%) and non-CSD (3.4%) melanomas. Of the 43 cases with mTOR mutations, 41 different mutations were detected, affecting 25 different exons. The median survival time for melanoma patients with mTOR nonsynonymous mutation was significantly shorter than that for patients without mTOR nonsynonymous mutation (P = 0.028). Transient expression of mTOR mutants in HEK293T cells strongly activated the mTOR–p70S6K pathway. In HEK293T cells with stable expression of H1968Y or P2213S mTOR mutants, LY294002 and AZD5363 showed higher potency than temsirolimus or BYL719 in inhibiting the PI3K–AKT–mTOR pathway and cell proliferation.

Conclusions: mTOR nonsynonymous mutations are frequent in melanoma patients. mTOR nonsynonymous mutation may predict a worse prognosis of melanoma. Clinical trials with PI3K–AKT–mTOR pathway inhibitors may be beneficial for melanoma patients with specific mTOR mutations. Clin Cancer Res; 22(4); 1018–27. ©2015 AACR.
A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
Authors: Papadopoulos Kyriakos P. , Kelley Robin Kate , Tolcher Anthony W. , Razak Albiruni R. Abdul , Van Loon Katherine , Patnaik Amita , Bedard Philippe L. , Alfaro Ariceli A. , Beeram Muralidhar , Adriaens Lieve , Brownstein Carrie M. , Lowy Israel , Kostic Ana , Trail Pamela A. , Gao Bo , DiCioccio A. Thomas , Siu Lillian L.
Published: October 2015

Purpose: Nesvacumab (REGN910) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds and inactivates the Tie2 receptor ligand Ang2 with high affinity, but shows no binding to Ang1. The main objectives of this trial were to determine the safety, tolerability, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D) of nesvacumab.

Experimental Design: Nesvacumab was administered intravenously every two weeks with dose escalations from 1 to 20 mg/kg in patients with advanced solid tumors.

Results: A total of 47 patients were treated with nesvacumab. No patients in the dose escalation phase experienced DLTs, therefore a maximum tolerated dose (MTD) was not reached. The most common nesvacumab-related adverse events were fatigue (23.4%), peripheral edema (21.3%), decreased appetite, and diarrhea (each 10.6%; all grade ≤ 2). Nesvacumab was characterized by linear kinetics and had a terminal half-life of 6.35 to 9.66 days in a dose-independent manner. Best response by RECIST 1.1 in 43 evaluable patients included 1 partial response (adrenocortical carcinoma) of 24 weeks duration. Two patients with hepatocellular carcinoma had stable disease (SD) > 16 weeks, with tumor regression and >50% decrease in α-fetoprotein. Analyses of putative angiogenesis biomarkers in serum and tumor biopsies were uninformative for treatment duration.

Conclusions: Nesvacumab safety profile was acceptable at all dose levels tested. Preliminary antitumor activity was observed in patients with treatment-refractory advanced solid tumors. On the basis of cumulative safety, antitumor activity, pharmacokinetic and pharmacodynamic data, the 20 mg/kg dose was determined to be the RP2D. Clin Cancer Res; 22(6); 1348–55. ©2015 AACR.
Skeptical Effectiveness: A Reply to Buford and Brueckner
Authors: Murphy Peter
Published: October 2015

In an earlier paper, I presented a novel objection to closure-based skeptical arguments. There I argued that the best account of what makes skeptical scenarios effective cripples the closure-based skeptical arguments that use those scenarios. On behalf of the skeptic, Christopher Buford and Anthony Brueckner have replied to my objection. Here I review my original argument, criticize their replies, and highlight two important issues for further investigation.
A new species of Geodiscelis Michener & Rozen (Hymenoptera: Colletidae: Xeromelissinae) from Peru
Authors: FERRARI RAFAEL R.
Published: October 2015

A new species of the bee genus Geodiscelis Michener & Rozen, 1999, G. antiminera sp. nov., is here described and illustrated. This is the sixth species of the genus, and the second recorded from Peru. The combination of malar area ~1.5x longer than wide, wing veins dark-brown, metepisternum nearly glabrous, and medioventral process on gonocoxa conical and well-developed, separates G. antiminera sp. nov. from all other Geodiscelis species. An updated identification key for all known species is provided. Phylogenetic analyses show that G. antiminera sp. nov. belongs to the subgenus Nazcoediscelis Packer & Dumesh, 2014 and is sister to the other three species in the subgenus.
Strongylovelia lillyae sp. nov. (Hemiptera: Gerromorpha: Veliidae) from Tamil Nadu, India: the first species of the genus described from the Indian subcontinent
Authors: JEHAMALAR E. EYARIN
Published: October 2015

Strongylovelia lillyae sp. nov. is described from Kanyakumari district, Tamil Nadu, India and constitutes the first species of the genus from Indian subcontinent. The new species is closely related to Strongylovelia setosa Zettel & Tran and S. vasarhelyii Zettel & Tran from Vietnam. A distribution map and photographs of S. lillyae sp. nov. are presented here.