bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling of ORL1 receptor-ligand interactions
Authors: Senćanski Milan , Ivanović Milovan , Došen-Mićović Ljiljana 
Published: April 2014

AbstractAn opioid receptor like (ORL1) receptor is one of a family of G-protein-coupled receptors (GPCR); it represents a new pharmaceutical target with extensive therapeutic potential for the regulation of important biological functions such as nociception, mood disorders, drug abuse, learning or cardiovascular control. Although the crystal structure of the inactive form of the ORL1 receptor has been determined, little is known about its activation. By using X-ray structures of the β2-adrenegic receptor in its inactive (2RH1) and active (3P0G) states as templates, inactive and active homology models of the ORL1 receptor were constructed. Structurally diverse sets of strongly binding antagonists and agonists were docked with both ORL1 receptor forms. The major receptor-ligand interactions responsible for antagonist and agonist binding were identified. Although both sets of ligands, agonists and antagonists, bind to the same region of the receptor, they occupy partially different binding pockets. Agonists bind to the inactive receptor in a slightly different manner than antagonists. This difference is more pronounced in binding to the active ORL1 receptor model and points to the amino acids at the extracellular end of TM6, suggesting that this region is important for receptor-activation.
Characterization of Platelet–Monocyte Complexes in HIV-1–Infected Individuals: Possible Role in HIV-Associated Neuroinflammation
Authors: Singh Meera V. , Davidson Donna C. , Jackson Joseph W. , Singh Vir B. , Silva Jharon , Ramirez Servio H. , Maggirwar Sanjay B. 
Published: April 2014

AbstractHIV-1–associated neuroinflammation persists even with effective combined antiretroviral therapy, and it is associated with the presence of activated monocytes/macrophages within the CNS. To infiltrate the CNS, monocytes transmigrate across the selectively permeable blood–brain barrier, which is compromised during HIV-1 infection. Interestingly, platelet-derived excess soluble CD40 ligand found in the plasma and cerebrospinal fluid of HIV-1–infected individuals with cognitive impairment has previously been implicated in increased blood–brain barrier permeability. In this study we show that soluble CD40 ligand also promotes the formation of complexes between inflammatory monocytes and activated platelets (PMCs), which are detected by flow cytometry as monocytes that express excess of CD61, a platelet marker, and that these complexes are increased in individuals with HIV-1 infection. PMCs exhibit an enhanced ability to adhere to human brain microvascular endothelial cells as compared with monocytes alone, and they migrate across the transendothelial barrier. These complexes can be found marginalized in the lumen of postcapillary venules in postmortem brain tissue derived from cases of HIV-1–associated encephalitis. The extravasation of monocytes across the brain endothelium may exacerbate neuroinflammation, indicating that enhancing this event via platelet interaction may be a contributing factor in the development of cognitive impairment. Thus, dampening platelet activation, and in turn PMC formation, with antiplatelet agents may prove beneficial in developing adjunctive therapies for use in combination with combined antiretroviral therapy in an effort to reduce HIV-1–associated neurologic deficit.
ATM Increases Activation-Induced Cytidine Deaminase Activity at Downstream S Regions during Class-Switch Recombination
Authors: Khair Lyne , Guikema Jeroen E. J. , Linehan Erin K. , Ucher Anna J. , Leus Niek G. J. , Ogilvie Colin , Lou Zhenkun , Schrader Carol E. , Stavnezer Janet 
Published: April 2014

Abstract
Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm−/− cells Sμ DSBs are increased, whereas DSBs in downstream Sγ regions are decreased. We also find that mutations in the unrearranged Sγ3 segment are reduced in atm−/− cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm−/− cells Sμ DSBs accumulate as they lack a recombination partner.
Economic Evaluation of an Eye Hospital in Terms of Net Present Value and Profitability Index
Authors: John Shibu , Dabas Komal , Naseem Iffat 
Published: April 2014

ABSTRACT

Introduction
Hospital projects are highly cost intensive and therefore, it takes few years to become a profit oriented entity. The success of these hospital projects can be measured through various economic evaluation methods. Economic evaluation can also be called as an effort to analyze inputs and outputs together and logically help decision makers evaluate whether a certain level of output is worth the amount of resources expended to produce it.

Method of the study
The present study was planned to do the economic evaluation of an Eye hospital, in Haryana state. Two parameters were considered for evaluating the project, i.e. Net Present Value (NPV) and Profitability Index (PI). The data used in the study was from 2010-2011 to 2016-2017. This includes actual and projected data.

Result and conclusion
A positive NPV explain the project is worthwhile and making profits, with current cost and revenue projections. PI for this center is found out to be 3.47 which also emphasize that the project is a value for money proposition.

How to cite this article
John S, Dabas K, Naseem I. Economic Evaluation of an Eye Hospital in Terms of Net Present Value and Profitability Index. Int J Res Foundation Hosp Healthc Adm 2014;2(1):36-40.
Sexual Harassment: A Growing Concern for Women in Indian Healthcare Industry
Authors: Singh Madhav Madhusudan , Patnaik Saroj Kumar , Prabhakaran Deepak , Srivastva Pradeep , Choudhary Pranav K 
Published: April 2014

ABSTRACT
Centuries of development in the field of medicine, has been one among the many indispensable major factors behind India's sky-high growth and overall prosperity. Medicine has evolved itself from being just a subject of applied sciences at clinical level to become an industry occupied in constantly increasing the life-expectancy of the man kind. The Indian healthcare industry has been making an immense contribution in improving the quality of healthcare and ancillary services to the second largest populous country in the world, which shall continue only if every employee is secured from work-place crimes like sexual harassment. An employee is considered to be a victim of sexual harassment when he or she is mentally or/and physically pressurized against his or her will to get sexually exploited by a co-employee or a superior at his or her work-place. The Indian Penal Code along with several legislations governing the Indian healthcare industry have recognized the seriousness of ‘sexual harassment at work-place’, calling for an immediate attention from both legal and medical fraternity.

How to cite this article
Singh MM, Patnaik SK, Prabhakaran D, Srivastva P, Choudhary PK. Sexual Harassment: A Growing Concern for Women in Indian Healthcare Industry. Int J Res Foundation Hosp Healthc Adm 2014;2(1):41-49.
Clustering mesoscale convective systems with laser‐based water vapor δ18O monitoring in Niamey (Niger)
Authors: Tremoy Guillaume , Vimeux Françoise , Soumana Salifou , Souley Ide , Risi Camille , Favreau Guillaume , Oï Monique 
Published: April 2014

AbstractThe isotopic composition of surface water vapor (δv) has been measured continuously in Niamey along with the isotopic composition of event‐based precipitation (δp) since 2010. We investigate the evolution of water vapor and precipitation isotope ratios during rain events of the 2010, 2011, and 2012 monsoon periods. We establish a classification of rain systems into three types based on the δv temporal evolution. We find that 51% of rain events (class A) exhibit a sharp decrease in δ18Ov in phase with the surface air temperature drop, leading to a depletion of water vapor by −1.9‰ on average during rainfall. Twenty‐nine percent of rain events (class B) show a similar decrease in δ18Ov in phase with the temperature drop but are characterized by a progressive enrichment of the vapor in the stratiform region, resulting in a depletion of water vapor by −1.2‰ on average during rainfall. The last 20% of the rain events (class C) are associated with a progressive increase in δ18Ov during rainfall (+0.8‰). We also examine the temporal evolution of water vapor deuterium excess (dv) which shows a sharp increase as δ18Ov decreases, followed by a progressive decrease in the stratiform part for classes A and B. Using a basic box model, we examine for each class the respective roles that mesoscale subsidence and rain evaporation play on the evolution of δ18Ov. We show that those two processes are dominant for class A, whereas other processes may exert a major role on δ18Ov for classes B and C.
Low concentration structural dynamics of lanreotide and somatostatin‐14
Authors: Hernández Belén , Coïc Yves‐Marie , Baron Bruno , Kruglik Sergei G. , Pflüger Fernando , Cohen Régis , Carelli Claude , Ghomi Mahmoud 
Published: April 2014

ABSTRACTLanreotide, a synthetic cyclic octapeptide, analogue of the peptide hormone somatostatin‐14 (SST‐14), is routinely used as a long‐acting medication in the management of neuroendocrine tumors. Despite its therapeutic importance, low concentration structural data is still lacking for lanreotide. In fact, the major part of the previous structural investigations were focused on the remarkable aggregation properties of this peptide, appearing at high concentrations (>5 mM). Here, we have applied three optical spectroscopic techniques, i.e. fluorescence, circular dichroism and Raman scattering, for analyzing the structural dynamics at the concentrations below 5 mM, where lanreotide exists either in a monomer state or at the first stages of aggregation. The obtained data from lanreotide were discussed through their comparison with those collected from SST‐14, leading us to the following conclusions: (i) The central D‐Trp residue, forming with its adjacent Lys the main receptor interacting part of lanreotide, keeps a constant high rotational freedom whatever the environment (water, water/methanol, methanol). (ii) A solvent‐dependent tight β‐turn, belonging to the type‐II' family, is revealed in lanreotide. (iii) Raman data analyzed by band decomposition in the amide (I and III) regions allowed estimation of different secondary structural elements within the millimolar range. Interestingly, the applied protocol shows a perfect agreement between the structural features provided by the amide I and amide III Raman markers. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 1019–1028, 2014.
Identification of novel biomass‐degrading enzymes from genomic dark matter: Populating genomic sequence space with functional annotation
Authors: Piao Hailan , Froula Jeff , Du Changbin , Kim Tae‐Wan , Hawley Erik R. , Bauer Stefan , Wang Zhong , Ivanova Nathalia , Clark Douglas S. , Klenk Hans‐Peter , Hess Matthias 
Published: April 2014

ABSTRACTAlthough recent nucleotide sequencing technologies have significantly enhanced our understanding of microbial genomes, the function of ∼35% of genes identified in a genome currently remains unknown. To improve the understanding of microbial genomes and consequently of microbial processes it will be crucial to assign a function to this “genomic dark matter.” Due to the urgent need for additional carbohydrate‐active enzymes for improved production of transportation fuels from lignocellulosic biomass, we screened the genomes of more than 5,500 microorganisms for hypothetical proteins that are located in the proximity of already known cellulases. We identified, synthesized and expressed a total of 17 putative cellulase genes with insufficient sequence similarity to currently known cellulases to be identified as such using traditional sequence annotation techniques that rely on significant sequence similarity. The recombinant proteins of the newly identified putative cellulases were subjected to enzymatic activity assays to verify their hydrolytic activity towards cellulose and lignocellulosic biomass. Eleven (65%) of the tested enzymes had significant activity towards at least one of the substrates. This high success rate highlights that a gene context‐based approach can be used to assign function to genes that are otherwise categorized as “genomic dark matter” and to identify biomass‐degrading enzymes that have little sequence similarity to already known cellulases. The ability to assign function to genes that have no related sequence representatives with functional annotation will be important to enhance our understanding of microbial processes and to identify microbial proteins for a wide range of applications. Biotechnol. Bioeng. 2014;111: 1550–1565. © 2014 Wiley Periodicals, Inc.
Identification of manipulated variables for a glycosylation control strategy
Authors: St. Amand Melissa M. , Radhakrishnan Devesh , Robinson Anne S. , Ogunnaike Babatunde A. 
Published: April 2014

ABSTRACTN‐linked glycan distribution affects important end‐use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. Yet, obtaining desired glycan distributions consistently during batch‐to‐batch production can be challenging for biopharmaceutical manufacturers. While an appropriately implemented on‐line glycosylation control strategy during production can help to ensure a consistent glycan distribution, to date no such strategies have been reported. Our goal is to develop and validate a comprehensive strategy for effective on‐line control of glycosylation, the successful achievement of which requires first identifying appropriate manipulated variables that can be used to direct the glycan distribution to a desired state. While various culture conditions such as bioreactor process variables, media type, and media supplements have been shown to affect the glycan distribution, in this study we focus on the latter. Specifically, we implemented a statistically designed series of experiments to determine the significant main effects (as well as interaction effects) of media supplementation with manganese, galactose, ammonia and found that each had significant effects on certain glycans. We also include data indicating the glycosylation enzyme gene transcript levels as well as the intracellular nucleotide sugar concentrations in the presence of the media supplements to provide insight into the intracellular conditions that may be contributing to the changes in glycan distribution. The acquired experimental data sets were then used to identify which glycans can be controlled by the media supplements and to what degree. We determined that MnCl2 can be used as a manipulated variable to increase the relative abundance of M51 and decrease FA2 simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. Biotechnol. Bioeng. 2014;111: 1957–1970. © 2014 Wiley Periodicals, Inc.
Reference and counter electrode positions affect electrochemical characterization of bioanodes in different bioelectrochemical systems
Authors: Zhang Fang , Liu Jia , Ivanov Ivan , Hatzell Marta C. , Yang Wulin , Ahn Yongtae , Logan Bruce E. 
Published: April 2014

ABSTRACTThe placement of the reference electrode (RE) in various bioelectrochemical systems is often varied to accommodate different reactor configurations. While the effect of the RE placement is well understood from a strictly electrochemistry perspective, there are impacts on exoelectrogenic biofilms in engineered systems that have not been adequately addressed. Varying distances between the working electrode (WE) and the RE, or the RE and the counter electrode (CE) in microbial fuel cells (MFCs) can alter bioanode characteristics. With well‐spaced anode and cathode distances in an MFC, increasing the distance between the RE and anode (WE) altered bioanode cyclic voltammograms (CVs) due to the uncompensated ohmic drop. Electrochemical impedance spectra (EIS) also changed with RE distances, resulting in a calculated increase in anode resistance that varied between 17 and 31 Ω (−0.2 V). While WE potentials could be corrected with ohmic drop compensation during the CV tests, they could not be automatically corrected by the potentiostat in the EIS tests. The electrochemical characteristics of bioanodes were altered by their acclimation to different anode potentials that resulted from varying the distance between the RE and the CE (cathode). These differences were true changes in biofilm characteristics because the CVs were electrochemically independent of conditions resulting from changing CE to RE distances. Placing the RE outside of the current path enabled accurate bioanode characterization using CVs and EIS due to negligible ohmic resistances (0.4 Ω). It is therefore concluded for bioelectrochemical systems that when possible, the RE should be placed outside the current path and near the WE, as this will result in more accurate representation of bioanode characteristics. Biotechnol. Bioeng. 2014;111: 1931–1939. © 2014 Wiley Periodicals, Inc.
Outcome of sleeve gastrectomy as a primary bariatric procedure
Authors: van Rutte P W J , Smulders J F , de Zoete J P , Nienhuijs S W 
Published: April 2014

Abstract

Background
Sleeve gastrectomy is being performed increasingly in Europe. Data on long-term outcome would be helpful in defining the role of sleeve gastrectomy. The aim of this study was to evaluate the outcome of sleeve gastrectomy as a primary bariatric procedure.

Methods
Medical charts of all patients who underwent a primary sleeve gastrectomy at the authors' institution between August 2006 and December 2012 were reviewed retrospectively using a prospective online data registry. For evolution of weight loss and co-morbidity, only patients with follow-up of at least 1 year were included. A subgroup analysis was done to compare patients with an intended stand-alone procedure and those with an intended two-stage procedure.

Results
A total of 1041 primary sleeve gastrectomies were performed in the study period. Median duration of surgery was 47 min, and median hospital stay was 2 days. Intra-abdominal bleeding occurred in 27 patients (2·6 per cent) and staple-line leakage in 24 (2·3 per cent). Some 866 patients had at least 1 year of follow-up. Mean excess weight loss was 68·4 per cent after 1 year (P &lt; 0·001) and 67·4 per cent after 2 years. Smaller groups of patients achieved a mean excess weight loss of 69·3 per cent (163 patients), 70·5 per cent (62) and 58·3 per cent (19) after 3, 4 and 5 years respectively. No difference in postoperative complications was found between the subgroups. Seventy-one (8·2 per cent) of 866 patients had a revision of the sleeve gastrectomy; reflux or dysphagia was the indication in 34 (48 per cent) of these patients.

Conclusion
Sleeve gastrectomy is a safe and effective bariatric procedure. Maximum weight loss was achieved after 4 years. Long-term results regarding weight loss and co-morbidities were satisfactory.
Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR
Authors: Tippin Brigette L. , Kwong Alan M. , Inadomi Michael J. , Lee Oliver J. , Park Jae Man , Materi Alicia M. , Buslon Virgilio S. , Lin Amy M. , Kudo Lili C. , Karsten Stanislav L. , French Samuel W. , Narumiya Shuh , Urade Yoshihiro , Salido Eduardo , Lin Henry J. 
Published: April 2014

AbstractOur earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in ApcMin/+ mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator‐activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced ApcMin/+ mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced ApcMin/+ mice expressing transgenic lipocalin‐type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30–40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in ApcMin/+ mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. ApcMin/+ mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v‐myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor‐suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.
Effects of correlated color temperature on focused and sustained attention under white LED desk lighting
Authors: Huang Rong‐Hwa , Lee Leemen , Chiu Yi‐An , Sun Yi 
Published: April 2014

AbstractSince the Kruithof's work on general illumination, the relationships between correlated color temperatures (CCTs) and human behavior are well documented. In the recent years, because of the high growth of light‐emitting diode (LED) lighting products, studies on the effects of LED lighting on human behavior have emerged. This study examines the effects of CCTs on focused and sustained attention under white LED desk lighting. Three CCT conditions (2700, 4300, and 6500 K) are examined, and the Chu Attention Test was used to measure focused and sustained attention. Results show that CCTs affect attention. In specific, the 4300 K condition resulted in a significantly better focused and sustained attention. Comfortableness and clarity are rated by the subjects. The self‐reported comfort shows no significant differences among the three conditions, but clarity shows significant differences. Gender differences are also discussed. It is found that the self‐reported clarity by males show no significant differences among the three lighting conditions, whereas the self‐reported clarity by females is significantly lower when CCT is 2700 K. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 281–286, 2015