bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using competition assays to quantitatively model cooperative binding by transcription factors and other ligands
Authors: Peacock Jacob , Jaynes James B. 
Published: August 2017

ABSTRACTBACKGROUNDThe affinities of DNA binding proteins for target sites can be used to model the regulation of gene expression. These proteins can bind to DNA cooperatively, strongly impacting their affinity and specificity. However, current methods for measuring cooperativity do not provide the means to accurately predict binding behavior over a wide range of concentrations.METHODSWe use standard computational and mathematical methods, and develop novel methods as described in Results.RESULTSWe explore some complexities of cooperative binding, and develop an improved method for relatingin vitromeasurements toin vivofunction, based on ternary complex formation. We derive expressions for the equilibria among the various complexes, and explore the limitations of binding experiments that model the system using a single parameter. We describe how to use single-ligand binding and ternary complex formation in tandem to determine parameters that have thermodynamic relevance. We develop an improved method for finding both single-ligand dissociation constants and concentrations simultaneously. We show how the cooperativity factor can be found when only one of the single-protein dissociation constants can be measured.CONCLUSIONSThe methods that we develop constitute an optimized approach to accurately model cooperative binding.GENERAL SIGNIFICANCEThe expressions and methods we develop for modeling and analyzing DNA binding and cooperativity are applicable to most cases where multiple ligands bind to distinct sites on a common substrate. The parameters determined using these methods can be fed into models of higher-order cooperativity to increase their predictive power.HIGHLIGHTSHill plots remain prominent in biology, but can mask cooperativityEffective modeling of binding by two ligands requires the use of 3 parametersWe develop novel ways to find these parameters for two cooperating ligandsWe show how they can be used to enhance the power of established methodsWe describe how this framework can be extended to multiple cooperating ligands
Identification of single pair of interneurons for bitter taste processing in theDrosophilabrain
Authors: Bohra Ali Asgar , Kallman Benjamin R , Reichert Heinrich , VijayRaghavan K. 
Published: August 2017

ABSTRACTDrosophilahas become an excellent model system for investigating the organization and function of the gustatory system due to the relatively simple neuroanatomical organization of its brain and the availability of powerful genetic and transgenic technology. Thus, at the molecular and cellular level, a great deal of insight into the peripheral detection and coding of gustatory information has already been attained. In contrast, much less is known about the central neural circuits that process this information and induce behaviorally appropriate motor output. Here we combine functional behavioral tests with targeted transgene expression through specific driver lines to identify a single bilaterally homologous pair of bitter sensitive interneurons that are located in the subesophageal zone of the brain. Anatomical and functional data indicate that these interneurons receive specific synaptic input from bitter sensitive gustatory receptor neurons. Targeted transgenic activation and inactivation experiments show that these bitter sensitive interneurons can largely suppress the proboscis extension reflex to appetitive stimuli such as sugar and water. These functional experiments together with calcium-imaging studies indicate that these first order local interneurons play an important role in the inhibition of the proboscis extension reflex that occurs in response to bitter tastants. Taken together, our studies present a cellular identification and functional characterization of a key gustatory interneuron in the bitter sensitive gustatory circuitry of the adult fly.
Lymphopenic community acquired pneumonia, an unnoticed phenotype associated to mortality in non immuno-suppressed patients: a retrospective cohort study
Authors: Bermejo-Martin Jesus F , Cilloniz Catia , Mendez Raul , Almansa Raquel , Gabarrus Albert , Ceccato Adrian , Torres Antoni , Menendez Rosario ,   for the NEUMONAC group
Published: August 2017

AbstractBackgroundThe role of neutrophil and lymphocyte counts as predictors of prognosis in Community Acquired Pneumonia (CAP) has not been appropriately studied.MethodsThis was a retrospective study to evaluate by multivariate regression analysis, the association between neutrophil and lymphocyte counts with mortality at 30-days post discharge in two large cohorts of hospitalized patients with CAP and no prior immunosupression: a multicentric with 1550 patients recruited at 14 hospitals in Spain and a unicentric with 2840 patients recruited at the Hospital Clinic-Barcelona.FindingsThe unicentric cohort accounted with a higher proportion of critically ill patients: 586 (20·6%) vs 131 (8·5%) and non survivors 245 (8·6%) vs 74 (4·8%). Lymphopenia (< 1000 lymphocytes/mm3) was present in the 52·8% of the patients in both cohorts. A sub-group of lymphopenic patients, those with lymphocyte counts below decil 3 (677 lymphocytes/mm3in the multicentric cohort and 651 lymphocytes/mm3in the unicentric one), showed > 2-fold increase in the risk of mortality, independently of the CURB-65 score, critical illness and receiving an appropriated antibiotic treatment: (OR [CI95%],p) (2·18 [1·21- 3·92], 0·009) and (2·33 [1·61-3·33], <0·001) respectively. Neutrophil counts were not associated with mortality risk.InterpretationLymphopenia is present in a half of the patients with CAP needing of hospitalization, in absence of antecendents of immunosupression. Lymphopenic CAP with lymphocyte counts < 664 lymphocytes/mm3constitutes a particular immunological phenotype of the disease which is associated to an increased risk of mortality.FundingCibeRes, 2009 Support to Research Groups of Catalonia 911, IDIBAPS, SEPAR, SVN
Refresh my memory: Episodic memory reinstatements intrude on working memory maintenance
Authors: Hoskin Abigail N. , Bornstein Aaron M. , Norman Kenneth A. , Cohen Jonathan D. 
Published: August 2017

AbstractA fundamental question in memory research is how different forms of memory interact. Previous research has shown that people rely on working memory (WM) in short-term recognition tasks; a common view is that episodic memory (EM) only influences performance on these tasks when WM maintenance is disrupted. However, retrieval of memories from EM has been widely observed during brief periods of quiescence, raising the possibility that EM retrievals during maintenance-critically, before a response can be prepared-might affect short-term recognition memory performance even in the absence of distraction. We hypothesized that this influence would be mediated by the lingering presence of reactivated EM content in WM. We obtained support for this hypothesis in three experiments, showing that delay-period EM reactivation introduces incidentally-associated information (context) into WM, and that these retrieved associations negatively impact subsequent recognition, leading to substitution errors (Experiment 1) and slowing of accurate responses (Experiment 2). fMRI pattern analysis showed that slowing is mediated by the content of EM reinstatement (Experiment 3). These results expose a previously hidden influence of EM on WM, raising new questions about the adaptive nature of their interaction.
Probe Efficient Feature Representation of Gapped K-mer Frequency Vectors from Sequences using Deep Neural Networks
Authors: Cao Zhen , Zhang Shihua 
Published: August 2017

AbstractHow to extract informative features from genome sequence is a challenging issue. Gapped k-mers frequency vectors (gkm-fv) has been presented as a new type of features in the last few years. Coupled with support vector machine (gkm-SVM), gkm-fvs have been used to achieve effective sequence-based predictions. However, the huge computation of a large kernel matrix prevents it from using large amount of data. And it is unclear how to combine gkm-fvs with other data sources in the context of string kernel. On the other hand, the high dimensionality, colinearity and sparsity of gkm-fvs hinder the use of many traditional machine learning methods without a kernel trick. Therefore, we proposed a flexible and scalable framework gkm-DNN to achieve feature representation from high-dimensional gkm-fvs using deep neural networks (DNN). We first proposed a more concise version of gkm-fvs which significantly reduce the dimension of gkm-fvs. Then we implemented an efficient method to calculate the gkm-fv of a given sequence at the first time. Finally, we adopted a DNN model with gkm-fvs as inputs to achieve efficient feature representation and a prediction task. Here, we took the transcription factor binding site prediction as an illustrative application. We applied gkm-DNN onto 467 small and 69 big human ENCODE ChIP-seq datasets to demonstrate its performance and compared it with the state-of-the-art method gkm-SVM. We demonstrated that gkm-DNN can not only improve the limitations of high dimensionality, colinearity and sparsity of gkm-fvs, but also make comparable overall performance compared with gkm-SVM using the same gkm-fvs. In addition, we used gkm-DNN to explore the representation power of gkm-fvs and provided more explanation on how gkm-fvs work.
Ch’ulel Mendoza, the spa with a difference: a case study of new product development in the wellness industry
Authors: Marano Gina , Henthorne Tony , George Babu 
Published: August 2017

Subject area
Hospitality and Tourism.

Study level/applicability
Senior undergraduate level and graduate level.

Case overview
This case study charts out the development of a business plan for Ch’ulel Mendoza, a hypothetical all-villa resort nestled against the Andes Mountains, where guests enjoy luxurious wine-infused spa treatments. The business plan has to be comprehensive because it should become the basis of a turnkey project for potential investors. Ch’ulel Mendoza is surrounded by the lush vineyards of some of the most famous wine estates in Argentina. The spa, facilities and services pay homage to the wine-growing heritage of the region, promoting wine to its guests as both pleasurable for consumption and conducive to healthy living. The architectural design speaks directly to the vines themselves: the earth-covered spa is where guests soak up the healing nutrients in the vinotherapy and water treatments, much like the roots are nourished by the elements and water in the soil; the resort area embraces the outdoors with decks, open patios and pools where guests can bask in the sun and enjoy other natural elements, just like the grape plants themselves. Once it becomes operational, Ch’ulel Mendoza will symbolize a blend of wellness, recreation and the charm of the Latin American culture.

Expected learning outcomes
Develop a comprehensive business plan for a new business, understand the business environment, prepare a strengths, weaknesses, opportunities and weaknesses analysis, develop functional (marketing, finance, human resources, operations, etc.) plans and understand the opportunities and challenges in the new product development process.

Subject code
CSS: 12: Tourism and Hospitality.
Role of heatlines on thermal management during Rayleigh-Bénard heating within enclosures with concave/convex horizontal walls
Authors: Biswal Pratibha , Basak Tanmay 
Published: August 2017

Purpose
This study aims to carry out the analysis of Rayleigh-Bénard convection within enclosures with curved isothermal walls, with the special implication on the heat flow visualization via the heatline approach.

Design/methodology/approach
The Galerkin finite element method has been used to obtain the numerical solutions in terms of the streamlines (ψ ), heatlines (Π), isotherms (θ), local and average Nusselt number (

Nut¯) for various Rayleigh numbers (103 ≤ Ra ≥ 105), Prandtl numbers (Pr = 0.015 and 7.2) and wall curvatures (concavity/convexity).

Findings
The presence of the larger fluid velocity within the curved cavities resulted in the larger heat transfer rates and thermal mixing compared to the square cavity. Case 3 (high concavity) exhibits the largest

Nut¯ at the low Ra for all Pr. At the high Ra,

Nut¯ is the largest for Case 3 (high concavity) at Pr = 0.015, whereas at Pr = 7.2,

Nut¯ is the largest for Case 1 (high concavity and convexity).

Practical implications
The results may be useful for the material processing applications.

Originality/value
The study of Rayleigh-Bénard convection in cavities with the curved isothermal walls is not carried out till date. The heatline approach is used for the heat flow visualization during Rayleigh-Benard convection within the curved walled enclosures for the first time. Also, the existence of the enhanced fluid and heat circulation cells within the curved walled cavities during Rayleigh-Benard heating is illustrated for the first time.
Making Washington Work: Legislative Entrepreneurship and the Personal Vote from the Gilded Age to the Great Depression
Authors: Finocchiaro Charles J. , MacKenzie Scott A. 
Published: August 2017

AbstractStudies of bill sponsorship in the modern Congress highlight the effects of constituency characteristics, seniority, and committee membership. These studies, however, are limited in their ability to assess the effects of institutions. We provide the first systematic study of bill sponsorship in the premodern House of Representatives. In doing so, we take advantage of this period's expansive legislative agenda and variation in electoral system rules. Using matching and event count models, we estimate the effects of institutions, electoral competition, and members’ institutional positions and political experiences on their sponsorship of different types of bills. We find that two reforms—the Australian ballot and nominating primary—increased sponsorship of bills designed to cultivate personal votes, thereby contributing to the growth in private legislation and bills aimed at local constituencies. Our results establish these reforms as a major event shaping lawmaking activity and, with it, the character of contemporary representation.
Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated mechanism
Authors: Brown B R , Lee E J , Snow P E , Vance E E , Iwakura Y , Ohno N , Miura N , Lin X , Brown G D , Wells C A , Smith J R , Caspi R R , Rosenzweig H L 
Published: August 2017

Summary
Uveitis (intraocular inflammation) is a leading cause of loss of vision. Although its aetiology is largely speculative, it is thought to arise from complex genetic–environmental interactions that break immune tolerance to generate eye-specific autoreactive T cells. Experimental autoimmune uveitis (EAU), induced by immunization with the ocular antigen, interphotoreceptor retinoid binding protein (IRBP), in combination with mycobacteria-containing complete Freund's adjuvant (CFA), has many clinical and histopathological features of human posterior uveitis. Studies in EAU have focused on defining pathogenic CD4+ T cell effector responses, such as those of T helper type 17 (Th17) cells, but the innate receptor pathways precipitating development of autoreactive, eye-specific T cells remain poorly defined. In this study, we found that fungal-derived antigens possess autoimmune uveitis-promoting function akin to CFA in conventional EAU. The capacity of commensal fungi such as Candida albicans or Saccharomyces cerevisae to promote IRBP-triggered EAU was mediated by Card9. Because Card9 is an essential signalling molecule of a subgroup of C-type lectin receptors (CLRs) important in host defence, we evaluated further the proximal Card9-activating CLRs. Using single receptor-deficient mice we identified Dectin-2, but not Mincle or Dectin-1, as a predominant mediator of fungal-promoted uveitis. Conversely, Dectin-2 activation by α-mannan reproduced the uveitic phenotype of EAU sufficiently, in a process mediated by the Card9-coupled signalling axis and interleukin (IL)-17 production. Taken together, this report relates the potential of the Dectin-2/Card9-coupled pathway in ocular autoimmunity. Not only does it contribute to understanding of how innate immune receptors orchestrate T cell-mediated autoimmunity, it also reveals a previously unappreciated ability of fungal-derived signals to promote autoimmunity.
Left‐Corner Parsing With Distributed Associative Memory Produces Surprisal and Locality Effects
Authors: Rasmussen Nathan E. , Schuler William 
Published: August 2017

AbstractThis article describes a left‐corner parser implemented within a cognitively and neurologically motivated distributed model of memory. This parser's approach to syntactic ambiguity points toward a tidy account both of surprisal effects and of locality effects, such as the parsing breakdowns caused by center embedding. The model provides an algorithmic‐level (Marr, 1982) account of these breakdowns: The structure of the parser's memory and the nature of incremental parsing produce a smooth degradation of processing accuracy for longer center embeddings, and a steeper degradation when they are nested, in line with recall observations by Miller and Isard (1964) and speed‐accuracy trade‐off observations by McElree et al. (2003). Modeling results show that this effect is distinct from the effects of ambiguity and exceeds the effect of mere sentence length.
Toward personalized and adaptive QoS assessments via context awareness
Authors: Barakat Lina , Taylor Phillip , Griffiths Nathan , Taweel Adel , Luck Michael , Miles Simon 
Published: August 2017

AbstractQuality of Service (QoS) properties play an important role in distinguishing between functionally equivalent services and accommodating the different expectations of users. However, the subjective nature of some properties and the dynamic and unreliable nature of service environments may result in cases where the quality values advertised by the service provider are either missing or untrustworthy. To tackle this, a number of QoS estimation approaches have been proposed, using the observation history available on a service to predict its performance. Although the context underlying such previous observations (and corresponding to both user and service related factors) could provide an important source of information for the QoS estimation process, it has only been used to a limited extent by existing approaches. In response, we propose a context‐aware quality learning model, realized via a learning‐enabled service agent, exploiting the contextual characteristics of the domain to provide more personalized, accurate, and relevant quality estimations for the situation at hand. The experiments conducted demonstrate the effectiveness of the proposed approach, showing promising results (in terms of prediction accuracy) in different types of changing service environments.
Visfatin mediates doxorubicin resistance in human non–small‐cell lung cancer via Akt‐mediated up‐regulation of ABCC1
Authors: Cao Zhili , Liang Naixin , Yang Huaxia , Li Shanqing 
Published: August 2017

AbstractObjectivesNon–small‐cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Increasing levels of visfatin are correlated with worse clinical prognosis of NSCLC. However, the effects of visfatin on drug resistant are still not well illustrated.Materials and methodsEffects of visfatin on drug resistant cells were checked by CCK‐8 kit. Gene and protein variations were measured by real‐time PCR and western blot analysis, respectively.ResultsOur present data confirmed that expression of visfatin was significantly increased in NSCLC cells and tissues. In addition, protein and mRNA expression of visfatin were significantly elevated in doxorubicin (Dox) resistance of NSCLC cells when compared with their corresponding sensitivity parental cells. Overexpression of visfatin can down‐regulate the Dox sensitivity of NSCLC cells and up‐regulate the mRNA and protein expression of ABCC1, while has no effect on ABCB1. Knockdown of visfatin can down‐regulate the expression of ABCC1 in Dox‐resistant NSCLC cells. Visfatin can increase the phosphorylation and nuclear localization of Akt in NSCLC cells. LY294002 can decrease the expression of multidrug resistance protein‐1 (MRP1) in NSCLC Dox‐resistant cells. Chromatin immunoprecipitation assays showed that overexpression of visfatin can significantly increase the binding of Akt with the promoter of ABCC1 in both A549 and H1793 cells.ConclusionsThese data showed that visfatin can decrease Dox sensitivity of NSCLC cells via activation of Akt/MRP1. It indicated that inhibition of visfatin signals might be a promising therapeutic strategy for the management of chemoresistance of NSCLC patients.
Drug‐related stigma and access to care among people who inject drugs in Vietnam
Authors: Lan Chiao‐Wen , Lin Chunqing , Thanh Duong Cong , Li Li 
Published: August 2017

AbstractIntroduction and AimsThere are considerable challenges faced by people with a history of injecting drug use (PWID) in Vietnam, including drug‐related stigma and lack of access to healthcare. Seeking and utilising healthcare, as well as harm reduction programs for PWID, are often hampered by drug‐related stigma. This study aimed to examine the impacts of drug‐related stigma on access to care and utilisation of harm reduction programs among PWID in Vietnam.Design and MethodsA cross‐sectional study was conducted in two provinces in Vietnam, Phú Thọ and Vinh Phúc. The study participants completed the survey by using Audio Computer‐Assisted Self‐Interview between late 2014 and early 2015. Linear multiple regression models and logistic regression models were used to assess the relationship among drug‐related stigma, access to care and utilisation of harm reduction programs, including methadone maintenance treatment (MMT) and needle exchange programs (NEP).ResultsA total of 900 PWID participated in this study. Drug‐related stigma was significantly associated with lower level of access to care, but not with utilisation of MMT or NEP. Older age was positively associated with higher levels of access to care. Levels of education were positively correlated with access to care, as well as utilisation of MMT and NEP.Discussion and ConclusionsThis study underscores the need for future interventions to reduce drug‐related stigma in society and in health‐care settings to improve PWID's utilisation of care services. Special attention should be paid to younger PWID and those with lower levels of education.
Leprosy – an overview of clinical features, diagnosis, and treatment
Authors: Fischer Marcellus 
Published: August 2017

SummaryLeprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely.The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO‐supported preventive measures and strategies play a key role in endemic areas.