Characterizing the Role of DNA Repair Proteins in Telomere Length Regulation and Maintenance: Fanconi Anemia Complementation Group C Protein and 8-Oxoguanine DNA Glycosylase

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what extent. Telomere shortening has been linked to rare human disorders that present with bone marrow failure including Fanconi anemia (FA). FANCC is one of the most commonly mutated FA genes in FA patients and the FANCC subtype tends to have a relatively early onset of bone marrow failure and hematologic malignancies. Here, we studied the role of Fancc in telomere length regulation in mice. We demonstrated that deletion of Fancc did not affect telomerase activity, telomere length or telomeric end-capping in mice with long telomeres. We also showed that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and promotes telomere recombination initiated by short telomeres. Telomere shortening has also been linked to human aging and cancer development, with oxidative stress as a major contributing factor. 8-oxo-7, 8-dihydroguanine is among the most common oxidative DNA lesions, and is substrates for OGG1-initiated DNA base excision repair. Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity. We demonstrated that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. We also examined if telomeric DNA is particularly susceptible to oxidative guanine damage and if telomere specific factors affect the incision of oxidized guanines by OGG1. We showed that the GGG sequence context of telomere repeats and certain telomere configurations may contribute to telomere vulnerability to oxidative DNA damage processing

The Inter-Store Mobility of Supermarket Shoppers

The allegiance of a particular customer, and the distribution across customers of strength of affiliation to a store are important indicators of store health. It is therefore important to understand the extent and determinants of shopper mobility among competing retailers. While shoppers often patronize many stores, they typically have a primary affiliation to a “main store” that captures the majority of their purchases. We examine, in detail, the tendencies of shoppers to transition away from the current main store and adopt another in its place. That is, rather than study all types of store switching behavior, we focus on the decision to change primary allegiance. The model is established in a discrete time hazard framework and estimated as random-effects probit. Data from 548 households taking 88,945 shopping trips among five stores are used to calibrate the model. We find that state dependence is prevalent with nearly three quarters of the shoppers showing progressive attachment to their current main store. Interestingly, this finding is not simply driven by location (i.e., because shoppers are captive to a single store based on geographical distance). More likely, shoppers are unwilling to give up the benefits of store-specific knowledge of assortment, layout and prices. Second, the decision to transition from a current main store is not influenced by temporary price promotions on a common basket of items: Shoppers will cherry-pick, but this alone does not cause them to change primary allegiance. The majority of transitions occur across competing stores of the same price format, which suggests “format loyalty” is an important aspect of shopper behavior. After controlling for unobserved heterogeneity, we find little relationship between observable demographics and the transition probability. We do, however, find that shoppers who spend more per trip are less likely to change main stores, as are less frequent shoppers. Implications for retail management strategy are discussed

Reduced Fine-Tuning in Supersymmetry with R-parity violation

Both electroweak precision measurements and simple supersymmetric extensions of the standard model prefer a mass of the Higgs boson less than the experimental lower limit of 114 GeV. We show that supersymmetric models with R parity violation and baryon number violation have a significant range of parameter space in which the Higgs dominantly decays to six jets. These decays are much more weakly constrained by current LEP analyses and would allow for a Higgs mass near that of the $Z$. In general, lighter scalar quark and other superpartner masses are allowed and the fine-tuning typically required to generate the measured scale of electroweak symmetry breaking is ameliorated. The Higgs would potentially be discovered at hadron colliders via the appearance of new displaced vertices. The lightest neutralino could be discovered by a scan of vertex-less events LEP I data.Comment: 5 pages, 2 figures. Significant detail added to the arguments regarding LEP limits - made more quantitative. Better figures used, plotting more physical quantities. Typos corrected and references updated. Conclusions unchange

USAGE OF NFT AS AN INSTRUMENT OF STORED VALUE AT A PRODUCT LEVEL AND AS PAYMENT MEANS

The present disclosure relates to (1) a system and a method of using NFTs as an instrument of stored value at a product level, (2) a system and a method of processing of payments by a POS from an NFT-enabled multichannel wallet, and (3) a system and a method of processing of payments by the POS in a processing order set by a consumer in an NFT-enabled multichannel wallet. The first method discloses a consumer purchasing product values from a merchant. Upon purchasing, the merchant sends the NFTs to the consumer. In response to receiving the NFTs from the merchant, the consumer stores the NFTs in a web enabled payment wallet for future use. While shopping for goods, the consumer may purchase one or more goods at the merchant and may add it to a shopping basket. Among the one or more goods added to the shopping basket, some goods may qualify for NFT credit. At checkout, the merchant scans all relevant NFTs and reduces basket price and marks the NFTs as “redeemed” or may pay with an NFT-enabled wallet that may automatically deduct items having a valid NFT and marks the NFTs as “redeemed”. In the second method, payment at POS may automatically split tender between available eligible NFTs, default payment cards and other payment means like UPI, net banking, or cash. In the third method, the consumer may set order of preference of payment channels by merchant or by date. Depending on the preference and other settings set by the consumer, the POS may process the payment

Role of appetitive phenotype trajectory groups on child body weight during a family-based treatment for children with overweight or obesity.

ObjectiveEmerging evidence suggests that individual appetitive traits may usefully explain patterns of weight loss in behavioral weight loss treatments for children. The objective of this study was to identify trajectories of child appetitive traits and the impact on child weight changes over time.MethodsSecondary data analyses of a randomized noninferiority trial conducted between 2011 and 2015 evaluated children's appetitive traits and weight loss. Children with overweight and obesity (mean age = 10.4; mean BMI z = 2.0; 67% girls; 32% Hispanic) and their parent (mean age = 42.9; mean BMI = 31.9; 87% women; 31% Hispanic) participated in weight loss programs and completed assessments at baseline, 3, 6,12, and 24 months. Repeated assessments of child appetitive traits, including satiety responsiveness, food responsiveness and emotional eating, were used to identify parsimonious grouping of change trajectories. Linear mixed-effects models were used to identify the impact of group trajectory on child BMIz change over time.ResultsOne hundred fifty children and their parent enrolled in the study. The three-group trajectory model was the most parsimonious and included a high satiety responsive group (HighSR; 47.4%), a high food responsive group (HighFR; 34.6%), and a high emotional eating group (HighEE; 18.0%). Children in all trajectories lost weight at approximately the same rate during treatment, however, only the HighSR group maintained their weight loss during follow-ups, while the HighFR and HighEE groups regained weight (adjusted p-value < 0.05).ConclusionsDistinct trajectories of child appetitive traits were associated with differential weight loss maintenance. Identified high-risk subgroups may suggest opportunities for targeted intervention and maintenance programs

Designing a Knowledge Management System – A Case Study of a Global Telecommunications Company

This paper focuses on the challenges a global telecommunication company faces in managing their existing knowledge management (KM) systems and planning for a new enterprise-wide knowledge management system (KMS). Data was collected from six user roles using three disparate knowledge repositories. The design requirements for a new enterprisewide knowledge management system are presented. This paper offers a contribution to the study of information science by providing empirical evidence to the design requirements of an enterprise-wide KMS