6 resultados para Transcription-translation feedback loops

em Aston University Research Archive


Relevância:

100.00% 100.00%

Publicador:

Resumo:

The tendency of managers to focus on short-term results rather than on sustained company success is of particular importance to retail marketing managers, because marketing activities involve expenditures which may only pay off in the longer term. To address the issue of myopic management, our study shows how the complexity of the service profit chain (SPC) can cause managers to make suboptimal decisions. Hence, our paper departs from past research by recognizing that understanding the temporal interplay between operational investments, employee satisfaction, customer satisfaction, and operating profit is essential to achieving sustained success. In particular, we intend to improve understanding of the functioning of the SPC with respect to time lags and feedback loops. Results of our large-scale longitudinal study set in a multi-outlet retail chain reveal time-lag effects between operational investments and employee satisfaction, as well as between customer satisfaction and performance. These findings, along with evidence of a negative interaction effect of employee satisfaction on the relationship between current performance and future investments, show the substantial risk of mismanaging the SPC. We identify specific situations in which the dynamic approach leads to superior marketing investment decisions, when compared to the conventional static view of the SCP. These insights provide valuable managerial guidance for effectively managing the SPC over time. © 2012 New York University.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Saturation mutagenesis is a powerful tool in modern protein engineering. This can allow the analysis of potential new properties thus allowing key residues within a protein to be targeted and randomised. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK) has inherent redundancy and disparities in residue representation. In this we describe the combination of ProxiMAX randomisation and CIS display for the use of generating novel peptides. Unlike other methods ProxiMAX randomisation does not require any intricate chemistry but simply utilises synthetic DNA and molecular biology techniques. Designed ‘MAX’ oligonucleotides were ligated, amplified and digested in an iterative cycle. Results show that randomised ‘MAX’ codons can be added sequentially to the base sequence creating a series of randomised non-degenerate codons that can subsequently be inserted into a gene. CIS display (Isogencia, UK) is an in vitro DNA based screening method that creates a genotype to phenotype link between a peptide and the nucleic acid that encodes it. The use of straight forward in vitro transcription/translation and other molecular biology techniques permits ease of use along with flexibility making it a potent screening technique. Using ProxiMAX randomisation in combination with CIS display, the aim is to produce randomised anti-nerve growth factor (NGF) and calcitonin gene-related (CGRP) peptides to demonstrate the high-throughput nature of this combination.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Cells and organisms respond to nutrient deprivation by decreasing global rates of transcription, translation and DNA replication. To what extent such changes can be reversed is largely unknown. We examined the effect of maternal dietary restriction on RNA synthesis in the offspring. Low protein diet fed either throughout gestation or for the preimplantation period alone reduced cellular RNA content across fetal somatic tissues during challenge and increased it beyond controls in fetal and adult tissues after challenge release. Changes in transcription of ribosomal RNA, the major component of cellular RNA, were responsible for this phenotype as evidenced by matching alterations in RNA polymerase I density and DNA methylation at ribosomal DNA loci. Cellular levels of the ribosomal transcription factor Rrn3 mirrored the rRNA expression pattern. In cell culture experiments, Rrn3 overexpression reduced rDNA methylation and increased rRNA expression; the converse occurred after inhibition of Rrn3 activity. These observations define novel mechanism where poor nutrition before implantation irreversibly alters basal rates of rRNA transcription thereafter in a process mediated by rDNA methylation and Rrn3 factor.

Relevância:

40.00% 40.00%

Publicador:

Resumo:

In this talk I discuss some of the problems involved in the transcription and translation of poor quality and/or covertly made recordings. My focus is on how Speech Act Theory can help inform transcription practice. I argue that transcribers should have a good understanding of the pragmatic level of language communication; I illustrate with real case examples how the lack of this understanding can lead to flawed interpretations (and thus potentially miscarriages of justice). I also discuss the problems inherent in forensic translation, where, given the evidential status of the material being translated, the translator’s linguistic choices are often circumscribed by elements of the legal context s/he may not be familiar with.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Translation training in the university context needs to train students in the processes, in order to enhance and optimise the product as outcome of these processes. Evaluation of a target text as product has often been accused of being a subjective process, which does not easily lend itself to the type of feedback that could enable students to apply criteria more widely. For students, it often seems as though they make different inappropriate or incorrect choices every time they translate a new text, and the learning process appears unpredictable and haphazard. Within functionalist approaches to translation, with their focus on the target text in terms of functional adequacy to the intended purpose, as stipulated in the translation brief, there are guidelines for text production that can help to develop a more systematic approach not only to text production, but also to translation evaluation. In the context of a focus on user knowledge needs, target language conventions and acceptability, the use of corpora is an indispensable tool for the trainee translator. Evaluation can take place against the student's own reasoned selection process, based on hard evidence, against criteria which currently obtain in the TL and the TL culture. When trainee and evaluator work within the same guidelines, there is more scope for constructive learning and feedback.