Quantifying environmental and financial benefits of using porters and cycle couriers for last-mile parcel delivery

Parcel carriers face increasingly difficult operating conditions in busy metropolitan areas due to growing consumer demand for ever faster delivery services and having to cope with traffic congestion and city authority measures that may restrict or penalise access for certain types of vehicle. This paper evaluates the potential environmental and financial benefits of switching from traditional van-based deliveries to an alternative operating model, where porters or cycle couriers undertake deliveries supported by a substantially reduced van fleet. Results using a specially-developed algorithm to model operations of a real carrier in an area of central London, UK, suggested that the carrier could reduce CO2 emissions by 45%, NOx emissions by 33%, driving distance by 78% and curbside parking time by 45%. Overall cost savings to the carrier were estimated to be in the range 34–39%. Scaling up the modelled emissions savings to London’s Central Activities Zone, an area of approximately 30 km2 and with current total annual parcel delivery distance of around 15 million km, could see annual emissions savings in the region of 2 million kg CO2 and 1633 kg NOx if all carriers utilised porters or cycle couriers. The key operating challenges identified were related to sorting and consolidating items by weight and volume, parcel handover arrangements and how to deal with express items and failed deliveries

Understanding the Impact of E-commerce on Last-Mile Light Goods Vehicle Activity in Urban Areas: The Case of London

Growth in e-commerce has led to increasing use of light goods vehicles for parcel deliveries in urban areas. This paper provides an insight into the reasons behind this growth and the resulting effort required to meet the exacting delivery services offered by e-retailers which often lead to poor vehicle utilisation in the last-mile operation, as well as the duplication of delivery services in urban centres as competitors vie for business. A case study investigating current parcel delivery operations in central London identified the scale of the challenge facing the last-mile parcel delivery driver, highlighting the importance of walking which can account for 62% of the total vehicle round time and 40% of the total round distance in the operations studied. The characteristics of these operations are in direct conflict with the urban infrastructure which is being increasingly redesigned in favour of walking, cycling and public transport, reducing the kerbside accessibility for last-mile operations. The paper highlights other pressures on last-mile operators associated with managing seasonal peaks in demand; reduced lead times between customers placing orders and deliveries being made; meeting delivery time windows; first-time delivery failure rates and the need to manage high levels of product returns. It concludes by describing a range of initiatives that retailers and parcel carriers, sometimes in conjunction with city authorities, can implement to reduce the costs associated with last-mile delivery, without negatively impacting on customer service levels

Posttranscriptional regulation of angiotensin II type 1 receptor expression by glyceraldehyde 3-phosphate dehydrogenase

Regulation of angiotensin II type 1 receptor (AT1R) has a pathophysiological role in hypertension, atherosclerosis and heart failure. We started from an observation that the 3′-untranslated region (3′-UTR) of AT1R mRNA suppressed AT1R translation. Using affinity purification for the separation of 3′-UTR-binding proteins and mass spectrometry for their identification, we describe glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an AT1R 3′-UTR-binding protein. RNA electrophoretic mobility shift analysis with purified GAPDH further demonstrated a direct interaction with the 3′-UTR while GAPDH immunoprecipitation confirmed this interaction with endogenous AT1R mRNA. GAPDH-binding site was mapped to 1–100 of 3′-UTR. GAPDH-bound target mRNAs were identified by expression array hybridization. Analysis of secondary structures shared among GAPDH targets led to the identification of a RNA motif rich in adenines and uracils. Silencing of GAPDH increased the expression of both endogenous and transfected AT1R. Similarly, a decrease in GAPDH expression by H2O2 led to an increased level of AT1R expression. Consistent with GAPDH having a central role in H2O2-mediated AT1R regulation, both the deletion of GAPDH-binding site and GAPDH overexpression attenuated the effect of H2O2 on AT1R mRNA. Taken together, GAPDH is a translational suppressor of AT1R and mediates the effect of H2O2 on AT1R mRNA

The scope for pavement porters: addressing the challenges of last-mile parcel delivery in London

The UK parcel sector generated almost £9 billion in revenue in 2015, with growth expected to increase by 15.6% in 2019 and is characterized by many independent players competing in an ‘everyone-delivers-everywhere’ culture leading to much replication of vehicle activity. With road space in urban centers being increasingly reallocated to pavement widening, bus and cycle lanes, there is growing interest in alternative solutions to the last-mile delivery problem. We make three contributions in this paper: firstly, through empirical analysis using carrier operational datasets, we quantify the characteristics of last-mile parcel operations and demonstrate the reliance placed on walking which can make up over 60% of the round time; secondly we introduce the concept of ‘portering’ where vans rendezvous with porters who operate within specific ‘patches’ to service consignees on-foot, potentially saving 86% in driving distance on some rounds; finally, we highlight the wider practical issues and optimization challenges associated with operating driving and portering rounds in inner urban areas

The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

Parasites are one of the strongest selective agents in nature. They select for hosts that evolve counter‐adaptive strategies to cope with infection. Helminth parasites are special because they can modulate their hosts’ immune responses. This phenomenon is important in epidemiological contexts, where coinfections may be affected. How different types of hosts and helminths interact with each other is insufficiently investigated. We used the three‐spined stickleback (Gasterosteus aculeatus) – Schistocephalus solidus model to study mechanisms and temporal components of helminth immune modulation. Sticklebacks from two contrasting populations with either high resistance (HR) or low resistance (LR) against S. solidus, were individually exposed to S. solidus strains with characteristically high growth (HG) or low growth (LG) in G. aculeatus. We determined the susceptibility to another parasite, the eye fluke Diplostomum pseudospathaceum, and the expression of 23 key immune genes at three time points after S. solidus infection. D. pseudospathaceum infection rates and the gene expression responses depended on host and S. solidus type and changed over time. Whereas the effect of S. solidus type was not significant after three weeks, T regulatory responses and complement components were upregulated at later time points if hosts were infected with HG S. solidus. HR hosts showed a well orchestrated immune response, which was absent in LR hosts. Our results emphasize the role of regulatory T cells and the timing of specific immune responses during helminth infections. This study elucidates the importance to consider different coevolutionary trajectories and ecologies when studying host‐parasite interactions

Impaired Embryonic Development in Mice Overexpressing the RNA-Binding Protein TIAR

TIA-1-related (TIAR) protein is a shuttling RNA-binding protein involved in several steps of RNA metabolism. While in the nucleus TIAR participates to alternative splicing events, in the cytoplasm TIAR acts as a translational repressor on specific transcripts such as those containing AU-Rich Elements (AREs). Due to its ability to assemble abortive pre-initiation complexes coalescing into cytoplasmic granules called stress granules, TIAR is also involved in the general translational arrest observed in cells exposed to environmental stress. However, the in vivo role of this protein has not been studied so far mainly due to severe embryonic lethality upon tiar invalidation.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Different modes of interaction by TIAR and HuR with target RNA and DNA

TIAR and HuR are mRNA-binding proteins that play important roles in the regulation of translation. They both possess three RNA recognition motifs (RRMs) and bind to AU-rich elements (AREs), with seemingly overlapping specificity. Here we show using SPR that TIAR and HuR bind to both U-rich and AU-rich RNA in the nanomolar range, with higher overall affinity for U-rich RNA. However, the higher affinity for U–rich sequences is mainly due to faster association with U-rich RNA, which we propose is a reflection of the higher probability of association. Differences between TIAR and HuR are observed in their modes of binding to RNA. TIAR is able to bind deoxy-oligonucleotides with nanomolar affinity, whereas HuR affinity is reduced to a micromolar level. Studies with U-rich DNA reveal that TIAR binding depends less on the 2′-hydroxyl group of RNA than HuR binding. Finally we show that SAXS data, recorded for the first two domains of TIAR in complex with RNA, are more consistent with a flexible, elongated shape and not the compact shape that the first two domains of Hu proteins adopt upon binding to RNA. We thus propose that these triple-RRM proteins, which compete for the same binding sites in cells, interact with their targets in fundamentally different ways

iCLIP Predicts the Dual Splicing Effects of TIA-RNA Interactions

Transcriptome-wide analysis of protein-RNA interactions predicts the dual splicing effects of TIA proteins, showing that their local enhancing function is associated with diverse distal splicing silencing effects

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field