bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective drug–protein interaction between mexiletine and plasma protein
Authors: Yu Lushan , Hong Yanjun , Li Li , Jin Yingxiu , Zheng Mingyue , Jiang Hualiang , Zeng Su 
Published: March 2012

Abstract

Objectives
This study examined the interaction of mexiletine enantiomers with human plasma, human serum albumin (HSA), and human α1-acid glycoprotein (hAGP), and characterized the binding modes of mexiletine enantiomers with hAGP in the molecular level.

Methods
Enantiomer separation of mexiletine was performed using precolumn derivatization chiral HPLC. The ultrafiltration technique was used to separate the free mexiletine in plasma matrix. Molecular dynamics simulations and free energy calculations were assessed using molecular mechanics and the generalized Born surface area method.

Key findings
Significant differences in enantioselective binding to human plasma were observed (R &gt; S). The hAGP–mexiletine binding profile exhibited similar enantioselectivity (R &gt; S) to that in human plasma, whereas HSA–mexiletine interaction was S &gt; R at pH 7.4. Moreover, the results of comparative studies indicated that mexiletine had the highest binding affinity for F1-S, a variant of hAGP. Based on the computational studies, residues such as Arg90, Leu79, Ser89 and Phe89 showed an energy difference of more than −0.35 kcal/mol between the enantiomers.

Conclusions
hAGP may be one of the key proteins leading to the enantioselective protein bindings of mexiletine in human plasma (R &gt; S). The residues Arg90, Leu79, Ser89 and Phe89 of hAGP may have important roles in the observed enantioselectivity.
Influenza Viruses Expressing Chimeric Hemagglutinins: Globular Head and Stalk Domains Derived from Different Subtypes
Authors: Hai Rong , Krammer Florian , Tan Gene S. , Pica Natalie , Eggink Dirk , Maamary Jad , Margine Irina , Albrecht Randy A. , Palese Peter 
Published: March 2012

ABSTRACT
The influenza virus hemagglutinin molecule possesses a globular head domain that mediates receptor binding and a stalk domain at the membrane-proximal region. We generated functional influenza viruses expressing chimeric hemagglutinins encompassing a variety of globular head and stalk combinations, not only from different hemagglutinin subtypes but also from different hemagglutinin phylogenetic groups. These chimeric recombinant viruses possess growth properties similar to those of wild-type influenza viruses and can be used as reagents to measure domain-specific antibodies in virological and immunological assays.
Superinfection Exclusion Is an Active Virus-Controlled Function That Requires a Specific Viral Protein
Authors: Folimonova Svetlana Y. 
Published: March 2012

ABSTRACT

Superinfection exclusion, a phenomenon in which a preexisting viral infection prevents a secondary infection with the same or a closely related virus, has been described for various viruses, including important pathogens of humans, animals, and plants. The phenomenon was initially used to test the relatedness of plant viruses. Subsequently, purposeful infection with a mild isolate has been implemented as a protective measure against virus isolates that cause severe disease. In the medical and veterinary fields, superinfection exclusion was found to interfere with repeated applications of virus-based vaccines to individuals with persistent infections and with the introduction of multicomponent vaccines. In spite of its significance, our understanding of this phenomenon is surprisingly incomplete. Recently, it was demonstrated that superinfection exclusion of
Citrus tristeza virus
(CTV), a positive-sense RNA closterovirus, occurs only between isolates of the same strain, but not between isolates of different strains of the virus. In this study, I show that superinfection exclusion by CTV requires production of a specific viral protein, the p33 protein. Lack of the functional p33 protein completely eliminated the ability of the virus to exclude superinfection by the same or a closely related virus. Remarkably, the protein appeared to function only in a homology-dependent manner. A cognate protein from a heterologous strain failed to confer the exclusion, suggesting the existence of precise interactions of the p33 protein with other factors involved in this complex phenomenon.
Plasticity and Virus Specificity of the Airway Epithelial Cell Immune Response during Respiratory Virus Infection
Authors: Ioannidis Ioannis , McNally Beth , Willette Meredith , Peeples Mark E. , Chaussabel Damien , Durbin Joan E. , Ramilo Octavio , Mejias Asuncion , Flaño Emilio 
Published: March 2012

ABSTRACT
Airway epithelial cells (AECs) provide the first line of defense in the respiratory tract and are the main target of respiratory viruses. Here, using oligonucleotide and protein arrays, we analyze the infection of primary polarized human AEC cultures with influenza virus and respiratory syncytial virus (RSV), and we show that the immune response of AECs is quantitatively and qualitatively virus specific. Differentially expressed genes (DEGs) specifically induced by influenza virus and not by RSV included those encoding interferon B1 (IFN-B1), type III interferons (interleukin 28A [IL-28A], IL-28B, and IL-29), interleukins (IL-6, IL-1A, IL-1B, IL-23A, IL-17C, and IL-32), and chemokines (CCL2, CCL8, and CXCL5). Lack of type I interferon or STAT1 signaling decreased the expression and secretion of cytokines and chemokines by the airway epithelium. We also observed strong basolateral polarization of the secretion of cytokines and chemokines by human and murine AECs during infection. Importantly, the antiviral response of human AECs to influenza virus or to RSV correlated with the infection signature obtained from peripheral blood mononuclear cells (PBMCs) isolated from patients with acute influenza or RSV bronchiolitis, respectively. IFI27 (also known as ISG12) was identified as a biomarker of respiratory virus infection in both AECs and PBMCs. In addition, the extent of the transcriptional perturbation in PBMCs correlated with the clinical disease severity. Our results demonstrate that the human airway epithelium mounts virus-specific immune responses that are likely to determine the subsequent systemic immune responses and suggest that the absence of epithelial immune mediators after RSV infection may contribute to explaining the inadequacy of systemic immunity to the virus.
Development of an Insect Vector Cell Culture and RNA Interference System To Investigate the Functional Role of Fijivirus Replication Protein
Authors: Jia Dongsheng , Chen Hongyan , Zheng Ailing , Chen Qian , Liu Qifei , Xie Lianhui , Wu Zujian , Wei Taiyun 
Published: March 2012

ABSTRACT

An
in vitro
culture system of primary cells from white-backed planthopper, an insect vector of Southern rice black-streaked dwarf virus (SRBSDV), a fijivirus, was established to study replication of the virus. Viroplasms, putative sites of viral replication, contained the nonstructural viral protein P9-1, viral RNA, outer-capsid proteins, and viral particles in virus-infected cultured insect vector cells, as revealed by transmission electron and confocal microscopy. Formation of viroplasm-like structures in non-host insect cells upon expression of P9-1 suggested that the matrix of viroplasms observed in virus-infected cells was composed basically of P9-1. In cultured insect vector cells, knockdown of P9-1 expression due to RNA interference (RNAi) induced by synthesized double-stranded RNA (dsRNA) from the
P9-1
gene strongly inhibited viroplasm formation and viral infection. RNAi induced by ingestion of dsRNA strongly abolished viroplasm formation, preventing efficient viral spread in the body of intact vector insects. All these results demonstrated that P9-1 was essential for viroplasm formation and viral replication. This system, combining insect vector cell culture and RNA interference, can further advance our understanding of the biological activities of fijivirus replication proteins.
Drug-induced movement disorders in children at paediatric emergency department: ‘dystonia’
Authors: Derinoz Oksan , Caglar Ayla Akca 
Published: March 2012

AimTo examine cases with drug-induced dystonic reactions (DIDRs), to identify the complaints of the application, to classify the drugs causing those dystonic reactions (DRs) and to determine the treatment options and protective measures to prevent DIDRs.MethodThe authors retrospectively analysed 55 cases with DIDRs at paediatric emergency department (PED) in a 5-year period.ResultsThe mean age of the patients was 145.07±56.30 months, and of the 55 cases, 28 cases (50.9%) were boys. Antiemetics and antipsychotics were the most common causes of DIDRs. 35 (70%) patients developed DIDRs at therapeutic doses. Treatment side effect was the most common cause of the DIDRs (78.2%). The most common DIDRs were abnormal postures of the head and neck (56.6%). Laryngospasm was observed only in four cases (7.3%) that used either antipsychotics or psychostimulants. 51 (92.7%) children were treated with parenteral diphenhydramine successfully.ConclusionDystonia is a common side effect of certain drugs, even when therapeutic doses are administered. Although the most common DIDRs were abnormal postures of the head and neck, rare life-threatening conditions, may develop particularly due to use of antipsychotics. In treatment, diphenhydramine could effectively be used through parenteral way to eliminate the cholinergic effects of those drugs. However, the easiest and the safest way to prevent the development of DRs is to avoid unnecessary drug usage. In conclusion, physicians should be aware that antiemetic and antipsychotic drugs are associated with DRs in normal doses and that those drugs should be prescribed with a correct indication.
Disneyland in Hong Kong — Green Challenge (A)
Authors: Tsai Terence , Liu Shubo Philip 
Published: March 2012

In mid-1999, the Walt Disney Company and the Hong Kong Government were involved in intense discussions about the possibility of building the Hong Kong Disneyland theme park on Lantau Island. This case presented detailed information about the proposed theme park and the associated decision making process with a particular emphasis on sustainable development. It also lays out the characteristics of the Hong Kong Government and Hong Kong people that might have played a role in decision making. The case includes A and B parts concerning corporate and government decision making. It firstly summarizes the negotiation process between Disney and the Hong Kong Government, and considered the environmental impact on Hong Kong. The difficulties faced by governments in making decisions about this highly visible large-scale project are described. It then explains the rationale of the government decision, which illustrates how governmental structure and culture affect the decision making process. In the end, it showed improvements in Hong Kong Disneyland with respect to sustainable management and development.
Leadership Development and Succession Planning at ICICI Bank
Authors: Kang Lakhwinder Singh , Sidhu Harpreet 
Published: March 2012

On 19 December 2008, ICICI bank named joint managing director Chanda Kochhar as its new CEO from May 2009 to lead India's second-largest lender at a time of declining market share, soaring bad debts and a tough global environment. She would be the successor of the 61-year-old visionary banker K. V. Kamath, MD and CEO of ICICI Bank who was to retire on 30 April 2009 after completing his successful tenure of 11 years. ICICI bank with a network of 1,456 branches and 4,721 ATMs in India and presence in 18 countries, is India's second-largest bank with total assets of Rs. 3,793.01 billion (US$75 billion) and profit after tax of Rs. 37.58 billion for the year ending March 31, 2009. It offers a wide range of banking products and financial services to corporate and retail customers. The need for succession planning arose at ICICI as the term of one top level executive ended, one other retired and two left the company. This case has been developed to provide understanding on how leaders are identified, nurtured and developed at ICICI bank, the strengths and weaknesses of CEO centric model of leadership development being followed by Kamath and the new institutionalized process of leadership development. It also provides the scope for discussion about the strengths and weaknesses of hiring an insider or outsider for the position of a CEO and the role of outgoing CEO in the development and selection of his/her successor.
GROWING HEARTS IN ASSOCIATIVE SYSTEMS
Authors: ANQUELA JOSÉ A. , CORTÉS TERESA 
Published: March 2012

We show that associative systems with a sufficiently good module structure imbed in a primitive system with simple primitive heart, spanned by the original system and the heart, so extending the results of J. Pure Appl. Algebra 181 (2003) 131–139 to systems over more general rings of scalars. We also study associative systems with involution.
LIE SUPERALGEBRAS WITH SOME HOMOGENEOUS STRUCTURES
Authors: AYADI IMEN , BENAMOR HEDI , BENAYADI SAÏD 
Published: March 2012

We generalize to the case of Lie superalgebras the classical symplectic double extension of symplectic Lie algebras introduced in [A. Aubert, Structures affines et pseudo-métriques invariantes à gauche sur des groupes de Lie, Thèse, Université Montpellier II (1996)]. We use this concept to give an inductive description of nilpotent homogeneous-symplectic Lie superalgebras. Several examples are included to show the existence of homogeneous quadratic symplectic Lie superalgebras other than even-quadratic even-symplectic considered in [E. Barreiro and S. Benayadi, Quadratic symplectic Lie superalgebras and Lie bi-superalgebras, J. Algebra 321(2) (2009) 582–608]. We study the structures of even (respectively, odd)-quadratic odd (respectively, even)-symplectic Lie superalgebras and odd-quadratic odd-symplectic Lie superalgebras and we give its inductive descriptions in terms of quadratic generalized double extensions and odd quadratic generalized double extensions. This study complete the inductive descriptions of homogeneous quadratic symplectic Lie superalgebras started in [E. Barreiro and S. Benayadi, Quadratic symplectic Lie superalgebras and Lie bi-superalgebras, J. Algebra 321(2) (2009) 582–608]. Finally, we generalize to the case of homogeneous quadratic symplectic Lie superalgebras some relations between even-quadratic even-symplectic Lie superalgebras and Manin superalgebras established in [E. Barreiro and S. Benayadi, Quadratic symplectic Lie superalgebras and Lie bi-superalgebras, J. Algebra 321(2) (2009) 582–608].
Loss of Transforming Growth Factor Beta Type II Receptor Increases Aggressive Tumor Behavior and Reduces Survival in Lung Adenocarcinoma and Squamous Cell Carcinoma
Authors: Malkoski Stephen P. , Haeger Sarah M. , Cleaver Timothy G. , Rodriguez Karen J. , Li Howard , Lu Shi-Long , Feser William J. , Barón Anna E. , Merrick Daniel , Lighthall Jessyka G. , Ijichi Hideaki , Franklin Wilbur , Wang Xiao-Jing 
Published: March 2012

Abstract
Purpose: Lung adenocarcinoma and lung squamous cell carcinoma (SCC) are the most common non–small cell lung cancer (NSCLC) subtypes. This study was designed to determine whether reduced expression of TGFβ type II receptor (TGFβRII) promotes lung adenocarcinoma and SCC carcinogenesis.
Experimental Design: We examined TGFβRII expression at the protein and mRNA levels in human NSCLC samples and assessed the relationship between TGFβRII expression and clinicopathologic parameters. To determine whether sporadic TGFβRII deletion in airway epithelial cells induces NSCLC formation, we targeted TGFβRII deletion alone and in combination with oncogenic KrasG12D to murine airways using a keratin 5 (K5) promoter and inducible Cre recombinase.
Results: Reduced TGFβRII expression in human NSCLC is associated with male gender, smoking, SCC histology, reduced differentiation, increased tumor stage, increased nodal metastasis, and reduced survival. Homozygous or heterozygous TGFβRII deletion in mouse airway epithelia increases the size and number of KrasG12D-initiated adenocarcinoma and SCC. TGFβRII deletion increases proliferation, local inflammation, and TGFβ ligand elaboration; TGFβRII knockdown in airway epithelial cells increases migration and invasion.
Conclusions: Reduced TGFβRII expression in human NSCLC is associated with more aggressive tumor behavior and inflammation that is, at least partially, mediated by increased TGFβ1 expression. TGFβRII deletion in mouse airway epithelial cells promotes adenocarcinoma and SCC formation, indicating that TGFβRII loss plays a causal role in lung carcinogenesis. That TGFβRII shows haploid insufficiency suggests that a 50% TGFβRII protein reduction would negatively impact lung cancer prognosis. Clin Cancer Res; 18(8); 2173–83. ©2012 AACR.
Focal Brain Lesions to Critical Locations Cause Widespread Disruption of the Modular Organization of the Brain
Authors: Gratton Caterina , Nomura Emi M. , Pérez Fernando , D'Esposito Mark 
Published: March 2012

AbstractAlthough it is generally assumed that brain damage predominantly affects only the function of the damaged region, here we show that focal damage to critical locations causes disruption of network organization throughout the brain. Using resting state fMRI, we assessed whole-brain network structure in patients with focal brain lesions. Only damage to those brain regions important for communication between subnetworks (e.g., “connectors”)—but not to those brain regions important for communication within sub-networks (e.g., “hubs”)—led to decreases in modularity, a measure of the integrity of network organization. Critically, this network dysfunction extended into the structurally intact hemisphere. Thus, focal brain damage can have a widespread, nonlocal impact on brain network organization when there is damage to regions important for the communication between networks. These findings fundamentally revise our understanding of the remote effects of focal brain damage and may explain numerous puzzling cases of functional deficits that are observed following brain injury.
Evaluation of WRF Mean and Extreme Precipitation over Spain: Present Climate (1970–99)
Authors: Argüeso Daniel , Hidalgo-Muñoz José Manuel , Gámiz-Fortis Sonia Raquel , Esteban-Parra María Jesús , Castro-Díez Yolanda 
Published: March 2012

Abstract
The ability of the Weather Research and Forecasting model (WRF) to simulate precipitation over Spain is evaluated from a climatological point of view. The complex topography and the large rainfall variability make the Iberian Peninsula a particularly interesting region and permit assessment of model performance under very demanding conditions.
Three high-resolution (10 km) simulations over the Iberian Peninsula have been completed spanning a 30-yr period (1970–99) and driven by different datasets: the 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) as “perfect boundary conditions” and two general circulation models (GCMs), the Max Planck Institute ECHAM5 model (ECHAM5/MPI) and the NCAR Community Climate System Model, version 3 (CCSM3). The daily precipitation observational grid Spain02 is employed to evaluate the model at varying time scales. Not only are the long-term means (annual, seasonal, and monthly) examined but also the high-order statistics (extreme events).
The WRF provides valuable information on precipitation at high resolution and enhances local spatial distribution due to orographic features. Although substantial errors are still observed in terms of monthly precipitation, especially during the spring, the model is largely able to capture the various precipitation regimes. The major benefits of using WRF are related to the spatial distribution of rainfall and the simulation of extreme events, two facets of climate that can be barely explored with GCMs.
This study shows that WRF can be a useful tool for generating high-resolution climate information for Spanish precipitation at spatial and temporal scales that are crucial for both the environment and human life.
Predicting the Snow-to-Liquid Ratio of Surface Precipitation Using a Bulk Microphysics Scheme
Authors: Milbrandt J. A. , Glazer A. , Jacob D. 
Published: March 2012

Abstract
Bulk microphysics parameterizations play an increasingly important role for quantitative precipitation forecasting (QPF) in operational numerical weather prediction (NWP). For wintertime, numerical prediction of snowfall amounts is done by applying an estimated snow-to-liquid ratio to the liquid-equivalent QPF from the NWP model. A method has been developed to use prognostic fields from a detailed bulk scheme to predict the instantaneous snow-to-liquid ratio of precipitating snow. By exploiting aspects of the parameterization of the large crystal/aggregate (snow) category, which allow for a prediction of the mean particle size and a corresponding realistic bulk density, combined with pristine ice and graupel fields, the total volume flux of ice-phase precipitation (excluding hail) is computed, independently from the computation of the total solid mass flux. Ultimately, the accumulated unmelted solid precipitation quantity is thus predicted without having to estimate the average snow-to-liquid ratio for a given event, as is typically done for wintertime QPF.
The new technique has been implemented into the two-moment version of the Milbrandt–Yau microphysics scheme, which was used in a high-resolution (2.5 and 1 km) NWP modeling system over the Vancouver–Whistler region of Canada in support of forecasting for the Vancouver 2010 Olympic and Paralympic Games. Experimental fields were produced including the instantaneous snow-to-liquid ratio and the snowfall accumulation predicted directly from the scheme using the new approach. Subjective evaluation indicates that the model can discriminate between low-density and high-density snow for instantaneous precipitation. Comparison of the predicted snow-to-liquid ratio to observed climatologies indicates that the scheme produces a realistic probability distribution.
Resident Confidence Addressing Social History
Authors: O’Toole Jennifer K. , Burkhardt Mary Carol , Solan Lauren G. , Vaughn Lisa , Klein Melissa D. 
Published: March 2012

Background Pediatric residency clinics caring for underserved populations are often staffed with varying levels of social and legal resources, though their effects on residents’ knowledge and practice have not been studied. Aim To examine the effects of clinic-based social and legal resources on resident knowledge and screening patterns for social determinants of health. Methods A cross-sectional study of residents from 3 continuity clinics with different social and legal resources was performed. Resident surveys assessing their knowledge and screening practices, and direct observation of social history taking was compared. Results Forty resident surveys revealed that those from clinics with more social and legal resources had greater confidence in their knowledge, screened more frequently, and spent more time taking social histories as assessed on direct observation. Conclusions Residents who practiced in continuity clinics with increased social and legal resources were more confident in their knowledge and screened for social determinants of health more frequently.