Global strategies to overcome the spiral of decline in universal bank markets

Although there has been an increase in the overall financial services market, the profitability of banks world-wide has decreased from the early 1980s to the 1990s. This has been attributed to several factors: the decline of traditional banking activities (deposit taking and lending); poorly performing debts (arising from poor lending decisions); and, for domestic banks, depressed property prices and important local industrial sectors performing badly. However, the analyses of bank performance tend to be short-term and narrow in their outlook, and seldom attempt to explain the underlying trends and processes of change. In this paper it is argued that the broad competitive forces of information technology, globalisation and deregulation are destabilising the banking industry leading to irrevocable changes which allow new entrants, disintermediation, innovation and customer changes on a much greater scale than has occurred in the past. These concepts are illustrated using a range of different bank markets as examples. To compete in these new markets different approaches are needed, and a series of possible strategies for addressing new bank markets are outlined with reference to size and type of bank. The long-term outlook for banking is discussed with particular attention being focussed on the changing role of universal banks

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag−/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.National Institutes of Health (U.S.) (NIH grant R01-CA075576)National Institutes of Health (U.S.) (NIH grant R01-CA055042)National Institutes of Health (U.S.) (NIH grant R01-CA149261)National Institutes of Health (U.S.) (NIH grant P30-ES00002)National Institutes of Health (U.S.) (NIH grant P30-ES02109)National Center for Research Resources (U.S.) (grant number M01RR-01066)National Center for Research Resources (U.S.) (grant number UL1 RR025758, Harvard Clinical and Translational Science Center

Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

The effects of seasonal demand on depot location

Many of the cost functions associated with depot location algorithms assume an overall demand for a fixed period, usually one year. This paper describes an investigation into the effect of high seasonality within such demand figures on the optimal location of storage facilities. The preliminary results indicate that a more flexible approach for certain products could be worthwhile.

The use of formal inventory control models: A preliminary survey

Of the many papers and texts on the subject of inventory control, relatively few report the successful implementation of systems based on formal mathematical models developed with specific objectives in mind. This could be considered rather strange in the light of the relatively high number of papers reporting the development of models for dealing with a multitude of different hypothetical situations, and the widespread availability of computer systems capable of exploiting such models. Various reasons for this anomaly can be put forward. This paper reports the results of a preliminary survey designed to investigate this more deeply, and draws some necessarily tentative conclusions relating to factors contributing to the successful application of such systems.