A genetically encodable cell-type-specific protein synthesis inhibitor

Chemical inhibitors have revealed requirements for protein synthesis that drive cellular plasticity. We developed a genetically encodable protein synthesis inhibitor (gePSI) to achieve cell-type-specific temporal control of protein synthesis. Controlled expression of the gePSI in neurons or glia resulted in rapid, potent and reversible cell-autonomous inhibition of protein synthesis. Moreover, gePSI expression in a single neuron blocked the structural plasticity induced by single-synapse stimulation

The translatome of neuronal cell bodies, dendrites,and axons

To form synaptic connections and store information, neurons continuously remodel their proteomes. The impressive length of dendrites and axons imposes logistical challenges to maintain synaptic proteins at locations remote from the transcription source (the nucleus). The discovery of thousands of messenger RNAs (mRNAs) near synapses suggested that neurons overcome distance and gain autonomy by producing proteins locally. It is not generally known, however, if, how, and when localized mRNAs are translated into protein. To investigate the translational landscape in neuronal subregions, we performed simultaneous RNA sequencing (RNA-seq) and ribosome sequencing (Ribo-seq) from microdissected rodent brain slices to identify and quantify the transcriptome and translatome in cell bodies (somata) as well as dendrites and axons (neuropil). Thousands of transcripts were differentially translated between somatic and synaptic regions, with many scaffold and signaling molecules displaying increased translation levels in the neuropil. Most translational changes between compartments could be accounted for by differences in RNA abundance. Pervasive translational regulation was observed in both somata and neuropil influenced by specific mRNA features (e.g., untranslated region [UTR] length, RNA-binding protein [RBP] motifs, and upstream open reading frames [uORFs]). For over 800 mRNAs, the dominant source of translation was the neuropil. We constructed a searchable and interactive database for exploring mRNA transcripts and their translation levels in the somata and neuropil [MPI Brain Research, The mRNA translation landscape in the synaptic neuropil. https://public.brain.mpg.de/dashapps/localseq/ Accessed 5 October 2021]. Overall, our findings emphasize the substantial contribution of local translation to maintaining synaptic protein levels and indicate that on-site translational control is an important mechanism to control synaptic strength

Continuum Model for River Networks

The effects of erosion, avalanching and random precipitation are captured in a simple stochastic partial differential equation for modelling the evolution of river networks. Our model leads to a self-organized structured landscape and to abstraction and piracy of the smaller tributaries as the evolution proceeds. An algebraic distribution of the average basin areas and a power law relationship between the drainage basin area and the river length are found.Comment: 9 pages, Revtex 3.0, 7 figures in compressed format using uufiles command, to appear in Phys. Rev. Lett., for an hard copy or problems e-mail to [email protected]

Measuring the sales impact of improving inventory records: How improving the accuracy of inventory records can grow sales by 4-8%

There is a growing body of evidence to suggest that retailers’ inventory records are inaccurate to a significant extent. And it is reasonable to assume that the higher the inventory record inaccuracy (IRI), the higher the impact on sales. But what does this mean in real terms? This report describes the outcome of a 3-year project (conducted with the participation of 7 of Europe’s largest retailers) the aim of which is to quantify the IRI problem and demonstrate the sales lift resulting from fixing it. A structured test-control type experiment is used, according to which test stores are subjected to stock counts at some particular point in time, whereas control stores are not, allowing us to measure the effect of reconciling (or not) the stock records on sales. The analysis covers approximately 1 Million stock keeping units (SKUs) sold in about 100 stores; such data is of a different order of magnitude to anything previously attempted in the academic and practitioner literature, leading to important, reliable and trustworthy conclusions. We find that about 60% of the SKUs analysed are affected by inventory record inaccuracies. We also find that positive IRI is as prevalent as negative IRI, with the same detrimental effects though on sales. Very importantly, correcting inventory inaccuracies is found to lead to approximately 4% to 8% of increased sales in the participating retailers. Interestingly, this applies to all retailers including the particularly ‘accurate’ ones. The results demonstrate that the biggest opportunity for improvement comes from high-volume expensive items, and detailed analysis by product category shows which categories should attract most attention. Finally, we discuss and show results on how inventory accuracy deteriorates over time following a stock count. This has implications for deciding how often and when stocktakes should take place. Our findings should be of great value to retailers to: i) inform their decisions on the appropriate levels of resource and investment against improving inventory records accuracy; ii) prioritise investments per product category and class; iii) appreciate the behaviour of positive and negative discrepancies; iv) discuss counting as a sales increase strategy rather than a cost-intensive necessity

Enriching demand forecasts with managerial information to improve inventory replenishment decisions: exploiting judgment and fostering learning

This paper is concerned with analyzing and modelling the effects of judgmental adjustments to replenishment order quantities. Judgmentally adjusting replenishment quantities suggested by specialized (statistical) software packages is the norm in industry. Yet, to date, no studies have attempted to either analytically model this situation or practically characterize its implications in terms of ‘learning’. We consider a newsvendor setting where information available to managers is reflected in the form of a signal that may or may not be correct, and which may or may not be trusted. We show the analytical equivalence of adjusting an order quantity and deriving an entirely new one in light of a necessary update of the estimated demand distribution. Further, we assess the system’s behavior through a simulation experiment on theoretically generated data and we study how to foster learning to efficiently utilize managerial information. Judgmental adjustments are found to be beneficial even when the probability of a correct signal is not known. More generally, some interesting insights emerge into the practice of judgmentally adjusting order quantities

Why the idea of framework propositions cannot contribute to an understanding of delusions

One of the tasks that recent philosophy of psychiatry has taken upon itself is to extend the range of understanding to some of those aspects of psychopathology that Jaspers deemed beyond its limits. Given the fundamental difficulties of offering a literal interpretation of the contents of primary delusions, a number of alternative strategies have been put forward including regarding them as abnormal versions of framework propositions described by Wittgenstein in On Certainty. But although framework propositions share some of the apparent epistemic features of primary delusions, their role in partially constituting the sense of inquiry rules out their role in helping to understand delusions

Inventory - forecasting: mind the gap

We are concerned with the interaction and integration between demand forecasting and inventory control, in the context of supply chain operations. The majority of the literature is fragmented. Forecasting research more often than not assumes forecasting to be an end in itself, disregarding any subsequent stages of computation that are needed to transform forecasts into replenishment decisions. Conversely, most contributions in inventory theory assume that demand (and its parameters) are known, in effect disregarding any preceding stages of computation. Explicit recognition of these shortcomings is an important step towards more realistic theoretical developments, but still not particularly helpful unless they are somehow addressed. Even then, forecasts often constitute exogenous variables that serially feed into a stock control model. Finally, there is a small but growing stream of research that is explicitly built around jointly tackling the inventory forecasting question. We introduce a framework to define four levels of integration: from disregarding, to acknowledging, to partly addressing, to fully understanding the interactions. Focusing on the last two, we conduct a structured review of relevant (integrated) academic contributions in the area of forecasting and inventory control and argue for their classification with regard to integration. We show that the development from one level to another is in many cases chronological in order, but also associated with specific schools of thought. We also argue that although movement from one level to another adds realism, it also adds complexity in terms of actual implementations, and thus a trade-off exists. The article makes a contribution into an area that has always been fragmented despite the importance of bringing the forecasting and inventory communities together to solve problems of common interest. We close with an indicative agenda for further research and a call for more theoretical contributions, but also more work that would help to expand the empirical knowledge base in this area