scholarly journals LINCS Data Portal 2.0: next generation access point for perturbation-response signatures

2019 ◽  
Vol 48 (D1) ◽  
pp. D431-D439 ◽  
Author(s):  
Vasileios Stathias ◽  
John Turner ◽  
Amar Koleti ◽  
Dusica Vidovic ◽  
Daniel Cooper ◽  
...  
Keyword(s):  
Large Scale ◽  
Access Point ◽  
Model Systems ◽  
Query Interface ◽  
Integrated Network ◽  
Data Architecture ◽  
Data Portal ◽  
The Individual ◽  
High Level ◽  
Point Level

Abstract The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program with the goal of generating a large-scale and comprehensive catalogue of perturbation-response signatures by utilizing a diverse collection of perturbations across many model systems and assay types. The LINCS Data Portal (LDP) has been the primary access point for the compendium of LINCS data and has been widely utilized. Here, we report the first major update of LDP (http://lincsportal.ccs.miami.edu/signatures) with substantial changes in the data architecture and APIs, a completely redesigned user interface, and enhanced curated metadata annotations to support more advanced, intuitive and deeper querying, exploration and analysis capabilities. The cornerstone of this update has been the decision to reprocess all high-level LINCS datasets and make them accessible at the data point level enabling users to directly access and download any subset of signatures across the entire library independent from the originating source, project or assay. Access to the individual signatures also enables the newly implemented signature search functionality, which utilizes the iLINCS platform to identify conditions that mimic or reverse gene set queries. A newly designed query interface enables global metadata search with autosuggest across all annotations associated with perturbations, model systems, and signatures.

Bribery and Corruption

2015 ◽  
pp. 196-210
Keyword(s):  
Large Scale ◽  
White Collar Crime ◽  
Public Officials ◽  
Government Officials ◽  
Decision Making Processes ◽  
Oil Contracts ◽  
The Individual ◽  
High Level ◽  
Personal Welfare ◽  
Political Economic

Bribes are mainly directed at government officials, although they could be directed at the employees and managers of business firms. However, bribery appears to be a self-defined crime. Bribery of small public sector employees is a white-collar crime. However, bribery also exists in high-level decision-making processes, whether political, economic, or corporate situations. These are large-scale bribes, consisting of millions and/or billions of dollars, paid out to executives and public officials in return for construction contracts, oil contracts, telecommunication contracts, etc. Although punishments exist and are implemented, it is up to the individual alone to make the final decision and choose between personal moral value system and personal welfare in opposition to serving the public welfare. This chapter explores bribery.

scholarly journals Detailed insight into the dynamics of the initial phases of de novo RNA-directed DNA methylation in plant cells

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Adéla Přibylová ◽  
Vojtěch Čermák ◽  
Dimitrij Tyč ◽  
Lukáš Fischer
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Model Systems ◽  
Transcriptional Gene Silencing ◽  
Epigenetic Mark ◽  
Gfp Reporter ◽  
Evolutionarily Conserved ◽  
The Individual ◽  
High Level ◽  
Rna Hairpin

Abstract Background Methylation of cytosines is an evolutionarily conserved epigenetic mark that is essential for the control of chromatin activity in many taxa. It acts mainly repressively, causing transcriptional gene silencing. In plants, de novo DNA methylation is established mainly by RNA-directed DNA-methylation pathway. Even though the protein machinery involved is relatively well-described, the course of the initial phases remains covert. Results We show the first detailed description of de novo DNA-methylation dynamics. Since prevalent plant model systems do not provide the possibility to collect homogenously responding material in time series with short intervals, we developed a convenient system based on tobacco BY-2 cell lines with inducible production of siRNAs (from an RNA hairpin) guiding the methylation machinery to the CaMV 35S promoter controlling GFP reporter. These lines responded very synchronously, and a high level of promoter-specific siRNAs triggered rapid promoter methylation with the first increase observed already 12 h after the induction. The previous presence of CG methylation in the promoter did not affect the methylation dynamics. The individual cytosine contexts reacted differently. CHH methylation peaked at about 80% in 2 days and then declined, whereas CG and CHG methylation needed more time with CHG reaching practically 100% after 10 days. Spreading of methylation was only minimal outside the target region in accordance with the absence of transitive siRNAs. The low and stable proportion of 24-nt siRNAs suggested that Pol IV was not involved in the initial phases. Conclusions Our results show that de novo DNA methylation is a rapid process initiated practically immediately with the appearance of promoter-specific siRNAs and independently of the prior presence of methylcytosines at the target locus. The methylation was precisely targeted, and its dynamics varied depending on the cytosine sequence context. The progressively increasing methylation resulted in a smooth, gradual inhibition of the promoter activity, which was entirely suppressed in 2 days.

Political Responsiveness in a Patronage Democracy

2019 ◽  
pp. 38-70
Author(s):  
Jennifer Bussell
Keyword(s):  
Large Scale ◽  
Local Level ◽  
Preliminary Evidence ◽  
Goods And Services ◽  
Local Politicians ◽  
Village Council ◽  
Primary Focus ◽  
Citizen Interactions ◽  
The Individual ◽  
High Level

This chapter draws on accounts from sustained, in-depth shadowing of Indian politicians, as well as large-scale politician surveys, to characterize the nature of politicians’ engagement with their constituents. It highlights the importance these politicians place on making time for citizen interactions and responding to requests—to the extent that high-level politicians spend, on average, a quarter of their time interacting with individual citizens. Critically, the primary focus of these contacts is requests for assistance with the same types of goods and services that are typically also requested of local politicians such as village council presidents, providing preliminary evidence that demands may at least partially originate from individuals’ failure to acquire these benefits at the local level—a topic to which the book later turns. Chapter 2 also shows that the individual benefits directly provided to citizens by high-level politicians are substantial.

scholarly journals Cereal resistance to Fusarium head blight and possibilities of its improvement through breeding

2009 ◽  
Vol 45 (No. 3) ◽  
pp. 87-105 ◽  
Author(s):  
K. Kosová ◽  
J. Chrpová ◽  
V. Šíp
Keyword(s):  
Fusarium Head Blight ◽  
Large Scale ◽  
Phenotypic Selection ◽  
Resistance Mechanisms ◽  
Head Blight ◽  
Cereal Breeding ◽  
Fhb Resistance ◽  
The Individual ◽  
Different Response ◽  
High Level

The aim of this review is to summarize recent information on Fusarium head blight (FHB) in small grain cereals, especially in wheat and barley. Basic information on FHB epidemiology, types of resistance and plant resistance mechanisms is included. Standard methods for the evaluation of the individual types of FHB resistance and the extent of infection are briefly described. Special attention is paid to the sources of FHB resistance of different origin and possibility of their exploitation in cereal breeding. Unfortunately, a high level of FHB resistance was detected in non-adapted germplasm or distant relatives, which is a serious impediment to breeding progress in this field. The present state of breeding for FHB resistance in wheat, barley, rye, triticale and oats was analyzed. It was shown that large-scale QTL detections provide new opportunities for increasing the resistance; however, multi-step phenotypic selection still remains to be the most effective tool. Pedigree analyses indicated that the latest progress reached in this field was obtained through the cumulation of resistance genes coming from heterogeneous sources with different response to FHB.

scholarly journals Data Portal for the Library of Integrated Network-based Cellular Signatures (LINCS) program: integrated access to diverse large-scale cellular perturbation response data

2017 ◽  
Vol 46 (D1) ◽  
pp. D558-D566 ◽  
Author(s):  
Amar Koleti ◽  
Raymond Terryn ◽  
Vasileios Stathias ◽  
Caty Chung ◽  
Daniel J Cooper ◽  
...  
Keyword(s):  
Large Scale ◽  
Integrated Network ◽  
Response Data ◽  
Data Portal

Bribery and Corruption

2015 ◽  
pp. 144-158
Author(s):  
Philippe W. Zgheib
Keyword(s):  
Large Scale ◽  
White Collar Crime ◽  
Public Officials ◽  
Government Officials ◽  
Decision Making Processes ◽  
Oil Contracts ◽  
The Individual ◽  
High Level ◽  
Personal Welfare ◽  
Political Economic

Bribes are mainly directed at government officials, although they could be directed at the employees and managers of business firms. However, bribery appears to be a self-defined crime. Bribery of small public sector employees is a white-collar crime. However, bribery also exists in high-level decision-making processes, whether political, economic, or corporate situations. These are large-scale bribes, consisting of millions and/or billions of dollars, paid out to executives and public officials in return for construction contracts, oil contracts, telecommunication contracts, etc. Although punishments exist and are implemented, it is up to the individual alone to make the final decision and choose between personal moral value system and personal welfare in opposition to serving the public welfare. This chapter explores bribery.

Czech Physical Planning at the Crossroads: Towards the Regulation of Large-Scale Retail Developments?

2010 ◽  
Vol 28 (2) ◽  
pp. 290-303 ◽  
Author(s):  
Jana Spilková ◽  
Radim Perlín
Keyword(s):  
Large Scale ◽  
Negotiation Process ◽  
Practical Application ◽  
Large Area ◽  
The Czech Republic ◽  
The Will ◽  
The Individual ◽  
High Level ◽  
Massive Development

The second half of the 1990s saw a dynamic development of Czech retailing and its spatial structure. Recent massive development of large-area commercial outlets in particular has revealed some problematic aspects and has also raised the question of whether their construction needs to be regulated. The role of local government in the decision processes concerning such developments is extremely weak and these processes are also complicated by a notably high level of bureaucracy. Although legislative documents proclaim the concept of sustainability as a key principle of future spatial development, its practical application will always depend on the will of the individual participants in the negotiation process. The authors argue that if a regulative approach to planning is chosen in the Czech Republic, planning offices must be respected bodies with enforceable rights and bound to act as strong authorities and effective agents of spatial plnning.

Social inequality in the evolution of human societies

2019 ◽  
pp. 98-120
Author(s):  
Georgi Derluguian
Keyword(s):  
Social Inequality ◽  
Large Scale ◽  
Human Beings ◽  
Mass Violence ◽  
Public And Private ◽  
Tangible Assets ◽  
Transition To Agriculture ◽  
New Institutions ◽  
High Level ◽  
Political Economic

The author develops ideas about the origin of social inequality during the evolution of human societies and reflects on the possibilities of its overcoming. What makes human beings different from other primates is a high level of egalitarianism and altruism, which contributed to more successful adaptability of human collectives at early stages of the development of society. The transition to agriculture, coupled with substantially increasing population density, was marked by the emergence and institutionalisation of social inequality based on the inequality of tangible assets and symbolic wealth. Then, new institutions of warfare came into existence, and they were aimed at conquering and enslaving the neighbours engaged in productive labour. While exercising control over nature, people also established and strengthened their power over other people. Chiefdom as a new type of polity came into being. Elementary forms of power (political, economic and ideological) served as a basis for the formation of early states. The societies in those states were characterised by social inequality and cruelties, including slavery, mass violence and numerous victims. Nowadays, the old elementary forms of power that are inherent in personalistic chiefdom are still functioning along with modern institutions of public and private bureaucracy. This constitutes the key contradiction of our time, which is the juxtaposition of individual despotic power and public infrastructural one. However, society is evolving towards an ever more efficient combination of social initiatives with the sustainability and viability of large-scale organisations.

Models, Practices and Methods of Reading: Evolution in Time and Space

2009 ◽  
pp. 59-64
Author(s):  
Yulia P. Melentyeva
Keyword(s):  
Large Scale ◽  
Social Groups ◽  
National Program ◽  
Time And Space ◽  
Lack Of Information ◽  
The Individual

In recent years as public in general and specialist have been showing big interest to the matters of reading. According to discussion and launch of the “Support and Development of Reading National Program”, many Russian libraries are organizing the large-scale events like marathons, lecture cycles, bibliographic trainings etc. which should draw attention of different social groups to reading. The individual forms of attraction to reading are used much rare. To author’s mind the main reason of such an issue has to be the lack of information about forms and methods of attraction to reading.

Excitonic Coupled-cluster Theory: Part I, General Formalism

2017 ◽  
Author(s):  
Yuhong Liu ◽  
Anthony Dutoi
Keyword(s):  
Electron Correlation ◽  
Degrees Of Freedom ◽  
Model Systems ◽  
Coupled Cluster ◽  
Effective Hamiltonian ◽  
Coupled Cluster Theory ◽  
Cluster Theory ◽  
Companion Article ◽  
High Level ◽  
Fragment Interaction

<div> <div>A shortcoming of presently available fragment-based methods is that electron correlation (if included) is described at the level of individual electrons, resulting in many redundant evaluations of the electronic relaxations associated with any given fluctuation. A generalized variant of coupled-cluster (CC) theory is described, wherein the degrees of freedom are fluctuations of fragments between internally correlated states. The effects of intra-fragment correlation on the inter-fragment interaction is pre-computed and permanently folded into the effective Hamiltonian. This article provides a high-level description of the CC variant, establishing some useful notation, and it demonstrates the advantage of the proposed paradigm numerically on model systems. A companion article shows that the electronic Hamiltonian of real systems may always be cast in the form demanded. This framework opens a promising path to build finely tunable systematically improvable methods to capture precise properties of systems interacting with a large number of other systems. </div> </div>

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