Assessing the Economic Gains from Telecom Competition

This paper develops and simulates a dynamic model of strategic telecom competition. The goal is to understand how regulatory policy, particularly relative to lease charges for local network elements, affects telecom competition, investment, retail prices, and consumer welfare. The model assumes two products, local voice service and data (broadband), and three types of players the regional Bell operating companies, referred to as incumbent local exchange carriers (ILECs), cable companies (Cables), and competitive local exchange carriers (CLECs). The game begins with a) ILECs established in each county with respect to the provision of local voice and data services and b) Cables established in roughly half of the counties with respect to the provision of data.There are one-time fixed costs of entering a county, product- and period-specific costs of operating in a county, and marginal costs of supplying each product. Economies of scope reduce the fixed entry and operating costs of supplying both products in a given county at a given point in time. Finally, in supplying telecom services in a given county, CLECs may enter by leasing ILEC infrastructure at specified access rates. The requirement that ILECs allow CLECs to lease their local network facilities was established in the Telecommunications Act of 1996 as part of a quid pro quo that promised ILECs entry into the long distance market. But the ILECs continue to contest the quid. The ILECs support their position by suggesting that leased access reduces telecom investment and output and raises telecom prices. Our model considers the entire range of options available to each of the players, but it reaches the opposite conclusion. Indeed, we find thatif UNE-P rates were set at the Supreme Court-approved total element long-run incremental cost (TELRIC) levels, telecom investment and employment outlays would increase by over one fifth in counties containing the majority of the U.S. population and by over 30 percent in counties containing almost a third of the population. The present value of telecom outlays over the next 5 and 20 years would rise by $71 billion and$155 billion, respectively. On average, the switch from actual to TELRIC UNE rates would lower local phone rates across the country's 3108 counties by $57 per year, generating annual total savings to consumers of$15 billion. Almost two fifths of the population would experience reductions in local phone rates of 20 percent or more. Over one fifth would experience rate reductions of 30 percent or more. These findings of price reductions are based on a fairly conservative parameterization of our model with respect to the specification of true ILEC and CLEC incremental long-run production costs.

Getting More from Less in Defined Benefit Plans: Three Levers for a Low-Return World

As global interest rates hover near historic lows, defined benefit pension plan sponsors must grapple with the prospect of lower investment returns. This paper examines three levers that can enhance portfolio outcomes in a low-return world. The levers include: increased contributions; reduced investment costs; and increased portfolio risk. We use portfolio simulations based on a stochastic asset class forecasting model to evaluate each lever according to two criteria—its magnitude of impact and the certainty that this impact will be realized. Our analysis indicates that increased contributions have the greatest and most certain impact. Reduced costs have a more modest, but equally certain impact. Increased risk can deliver a significant impact, but with the least certainty

Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes

The adenosine monophosphate (AMP)–activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKα1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca2+ with Ca2+ ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca2+ stimulation of AMPK required the activity of Ca2+–calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca2+ signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it

Distinct conformations, aggregation and cellular internalization of different tau strains

The inter-cellular propagation of tau aggregates in several neurodegenerative diseases involves, in part, recurring cycles of extracellular tau uptake, initiation of endogenous tau aggregation, and extracellular release of at least part of this protein complex. However, human brain tau extracts from diverse tauopathies exhibit variant or “strain” specificity in inducing inter-cellular propagation in both cell and animal models. It is unclear if these distinctive properties are affected by disease-specific differences in aggregated tau conformation and structure. We have used a combined structural and cell biological approach to study if two frontotemporal dementia (FTD)-associated pathologic mutations, V337M and N279K, affect the aggregation, conformation and cellular internalization of the tau four-repeat domain (K18) fragment. In both heparin-induced and native-state aggregation experiments, each FTD variant formed soluble and fibrillar aggregates with remarkable morphological and immunological distinctions from the wild type (WT) aggregates. Exogenously-applied oligomers of the FTD tau-K18 variants (V337M and N279K) were significantly more efficiently taken up by SH-SY5Y neuroblastoma cells than WT tau-K18, suggesting mutation-induced changes in cellular internalization. However, shared internalization mechanisms were observed: endocytosed oligomers were distributed in the cytoplasm and nucleus of SH-SY5Y cells and the neurites and soma of human induced pluripotent stem cell-derived neurons where they co-localized with endogenous tau and the nuclear protein nucleolin. Altogether, evidence of conformational and aggregation differences between WT and disease-mutated tau K18 is demonstrated, which may explain their distinct cellular internalization potencies. These findings may account for critical aspects of the molecular pathogenesis of tauopathies involving WT and mutated tau

Analysis of the effect of Bacillus velezensis culture filtrate on the growth and proteome of Cladobotryum mycophilum

Cladobotryum mycophilum, the causative agent of cobweb disease on Agaricus bisporus results in significant crop losses for mushroom growers worldwide. Cobweb disease is treated through strict hygiene control methods and the application of chemical fungicides but an increase in fungicide resistant Cladobotryum strains has resulted in a need to develop alternative biocontrol treatment methods. The aim of the work presented here was to evaluate the response of C. mycophilum to a Bacillus velezensis isolate to assess its potential as a novel biocontrol agent. Exposure of 48 hr C. mycophilum cultures to 25% v/v 96 hr B. velezensis culture filtrate resulted in a 57% reduction in biomass (P < 0.0002), a disruption in hyphal structure and morphology, and the appearance of aurofusarin, a secondary metabolite which is a known indicator of oxidative stress, in culture medium. Proteomic analysis of B. velezensis culture filtrate revealed the presence of peptidase 8 (subtilisin), peptide deformylase and probable cytosol aminopeptidase which are known to induce catalytic activity. Characterisation of the proteomic response of C. mycophilum following exposure to B. velezensis culture filtrate revealed an increase in the abundance of a variety of proteins associated with stress response (ISWI chromatin-remodelling complex ATPase ISW2 (+24 fold), carboxypeptidase Y precursor (+3 fold) and calmodulin (+2 fold). There was also a decrease in the abundance of proteins associated with transcription (40 S ribosomal protein S30 (−26 fold), 40 S ribosomal protein S21 (−3 fold) and carbohydrate metabolism (l-xylulose reductase (−10 fold). The results presented here indicate that B. velezensis culture filtrate is capable of inhibiting the growth of C. mycophilum and inducing a stress response, thus indicating its potential to control this important pathogen of mushrooms

Characterising the proteomic response of mushroom pathogen Lecanicillium fungicola to Bacillus velezensis QST 713 and Kos biocontrol agent

The fungal pathogen Lecanicillium fungicola causes dry bubble disease in Agaricus bisporus cultivation and affected mushrooms significantly reduce the yield and revenue for mushroom growers. Biocontrol agents may represent an alternative and more environmentally friendly treatment option to help control dry bubble on mushroom farms. Serenade ® is a commercially available biocontrol product used for disease treatment in plant crops. In this work, the in vitro response of L. fungicola to the bacterial strain active in Serenade, Bacillus velezensis (QST 713) and a newly isolated B. velezensis strain (Kos) was assessed. B. velezensis (QST713 and Kos) both produced zones of inhibition on plate cultures of L. fungicola, reduced the mycelium growth in liquid cultures and damaged the morphology and structure of L. fungicola hyphae. The proteomic response of the pathogen against these biocontrol strains was also investigated. Proteins involved in growth and translation such as 60S ribosomal protein L21-A (−32- fold) and 40S ribosomal protein S30 (−17-fold) were reduced in abundance in B. velezensis QST 713 treated samples, while proteins involved in a stress response were increased (norsolorinic acid reductase B (47-fold), isocitrate lyase (11-fold) and isovaleryl-CoA dehydrogenase (8-fold). L. fungicola was found to have a similar proteomic response when exposed to B. velezensis (Kos). This work provides information on the response of L. fungicola to B. velezensis (QST 713) and indicates the potential of B. velezensis Kos as a novel biocontrol agent