Predictive Customer Lifetime value modeling: Improving customer engagement and business performance

CookUnity, a meal subscription service, has witnessed substantial annual revenue growth over the past three years. However, this growth has primarily been driven by the acquisition of new users to expand the customer base, rather than an evident increase in customers' spending levels. If it weren't for the raised subscription prices, the company's customer lifetime value (CLV) would have remained the same as it was three years ago. Consequently, the company's leadership recognizes the need to adopt a holistic approach to unlock an enhancement in CLV. The objective of this thesis is to develop a comprehensive understanding of CLV, its implications, and how companies leverage it to inform strategic decisions. Throughout the course of this study, our central focus is to deliver a fully functional and efficient machine learning solution to CookUnity. This solution will possess exceptional predictive capabilities, enabling accurate forecasting of each customer's future CLV. By equipping CookUnity with this powerful tool, our aim is to empower the company to strategically leverage CLV for sustained growth. To achieve this objective, we analyze various methodologies and approaches to CLV analysis, evaluating their applicability and effectiveness within the context of CookUnity. We thoroughly explore available data sources that can serve as predictors of CLV, ensuring the incorporation of the most relevant and meaningful variables in our model. Additionally, we assess different research methodologies to identify the top-performing approach and examine its implications for implementation at CookUnity. By implementing data-driven strategies based on our predictive CLV model, CookUnity will be able to optimize order levels and maximize the lifetime value of its customer base. The outcome of this thesis will be a robust ML solution with remarkable prediction accuracy and practical usability within the company. Furthermore, the insights gained from our research will contribute to a broader understanding of CLV in the subscription-based business context, stimulating further exploration and advancement in this field of study

Coral Reef Resilience Index for Novel Ecosystems: A Spatial Planning Tool for Managers and Decision Makers - A Case Study from Puerto Rico

Timely information is critical for coral reef managers and decision-makers to implement sustainable management measures. A Coral Reef Resilience Index (CRRI) was developed with a GIS-coupled decision-making tool applicable for Caribbean coral reef ecosystems. The CRRI is based on a five-point scale parameterized from the quantitative characterization of benthic assemblages. Separate subindices such as the Coral Index, the Threatened Species Index, and the Algal Index also provide specific information regarding targeted benthic components. This case study was based on assessments conducted in 2014 on 11 reef sites located across 3 geographic zones and 3 depth zones along the southwestern shelf of the island of Puerto Rico, Caribbean Sea. There was a significant spatial and bathymetric gradient (p < 0.05) in the distribution of CRRI values indicating higher degradation of inshore reefs. Mean global CRRI ranged from 2.78 to 3.17 across the shelf, ranking them as “fair.” The Coral Index ranged from 2.60 to 3.76, ranking reefs from “poor” to “good,” showing a general cross-shelf trend of improving conditions with increasing distance from pollution sources. Turbidity and ammonia were significantly correlated to CRRI scores. Multiple recommendations are provided based on coral reef conditions according to observed CRRI rankings

Volcanism and climate change as drivers in Holocene depositional dynamic of Laguna del Maule (Andes of central Chile – 36° S)

Late Quaternary volcanic basins are active landscapes from which detailed archives of past climate and seismic and volcanic activity can be obtained. A multidisciplinary study performed on a transect of sediment cores was used to reconstruct the depositional evolution of the high-elevation Laguna del Maule (LdM) (36∘ S, 2180 m a.s.l., Chilean Andes). The recovered 5 m composite sediment sequence includes two thick turbidite units (LT1 and LT2) and numerous tephra layers (23 ash and 6 lapilli). We produced an age model based on nine new 14C AMS dates, existing 210Pb and 137Cs data, and the Quizapú ash horizon (1932 CE). According to this age model, the relatively drier Early Holocene was followed by a phase of increased productivity during the mid-Holocene and higher lake levels after 4.0 ka cal BP. Major hydroclimate transitions occurred at ca. 11, 8.0, 4.0 and 0.5 ka cal BP. Decreased summer insolation and winter precipitation due to a southward shift in the southern westerly winds and a strengthened Pacific Subtropical High could explain Early Holocene lower lake levels. Increased biological productivity during the mid-Holocene (∼8.0 to 6.0 ka cal BP) is coeval with a warm–dry phase described for much of southern South America. Periods of higher lake productivity are synchronous to a higher frequency of volcanic events. During the Late Holocene, the tephra layers show compositional changes suggesting a transition from silica-rich to silica-poor magmas at around 4.0 ka cal BP. This transition was synchronous with increased variability of sedimentary facies and geochemical proxies, indicating higher lake levels and increased moisture at LdM after 4.0 ka cal BP, most likely caused by the inception of current El Niño–Southern Oscillation and Pacific Decadal Oscillation (ENSO–PDO) dynamics in central Chile.Postprin

Multi-Omics Integration Highlights the Role of Ubiquitination in CCl4-Induced Liver Fibrosis

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination is a post-translational modification that is crucial for a plethora of physiological processes. Even though the ubiquitin system has been implicated in several human diseases, the role of ubiquitination in liver fibrosis remains poorly understood. Here, multi-omics approaches were used to address this. Untargeted metabolomics showed that carbon tetrachloride (CCl4)-induced liver fibrosis promotes changes in the hepatic metabolome, specifically in glycerophospholipids and sphingolipids. Gene ontology analysis of public deposited gene array-based data and validation in our mouse model showed that the biological process “protein polyubiquitination” is enriched after CCl4-induced liver fibrosis. Finally, by using transgenic mice expressing biotinylated ubiquitin (bioUb mice), the ubiquitinated proteome was isolated and characterized by mass spectrometry in order to unravel the hepatic ubiquitinated proteome fingerprint in CCl4-induced liver fibrosis. Under these conditions, ubiquitination appears to be involved in the regulation of cell death and survival, cell function, lipid metabolism, and DNA repair. Finally, ubiquitination of proliferating cell nuclear antigen (PCNA) is induced during CCl4-induced liver fibrosis and associated with the DNA damage response (DDR). Overall, hepatic ubiquitome profiling can highlight new therapeutic targets for the clinical management of liver fibrosis.This work was supported by grants from Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C.), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M.-C.), Ministerio de Ciencia, Innovación y Universidades MICINN: SAF2017-87301-R, SAF2017-88041-R, RTI2018-096759-A-100 and SAF2016-76898-P integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (to M.L.M.-C., J.M.M., T.C.D. and U.M. respectively); AECC Bizkaia (M.S.-M.); Asociación Española contra el Cáncer (T.C.D.), Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M., J.M.B., M.A.A., J.J.G.M.), La Caixa Foundation Program (to M.L.M.), 2018 BBVA Foundation Grants for Scientific Research Teams (to M.L.M.-C.). This research was also funded by the CIBERehd (EHD15PI05/2016) and “Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III”, Spain (PI16/00598 and PI19/00819, co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-75197-R); “Junta de Castilla y Leon” (SA063P17); AECC Scientific Foundation (2017/2020), Spain; “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain; University of Salamanca Foundation, Spain (PC-TCUE18-20_051), and Fundació Marato TV3 (Ref. 201916-31), Spain (to J.J.G.M.). The UPV/EHU Lab and the Proteomics Platform are members of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I + D + i 2013-2016, funded by ISCIII and ERDF. Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury

Factors affecting survival in Mediterranean populations of the Eurasian eagle owl

The survival rate is a key parameter for population management and the monitoring of populations. Thus, an analysis of survival rate variations and the factors influencing the same is essential for understanding population dynamics. Here, we study the factors determining the survival and the causes of mortality of the Eurasian eagle owl (Bubo bubo) in two Spanish Mediterranean populations (Murcia and Seville) where the species has a high population density and breeding success; yet its survival rates and the factors that affect them are unknown. Between 2003 and 2010, 63 breeding owls were captured and radio-tracked. Three monthly (quarterly) survival rates were estimated using known-fate models in the program MARK. The mean overall annual survival rate was 0.776 (95 % CI: 0.677, 0.875). We observed survival differences between sexes, and between the breeding and non-breeding periods, although no overwhelming support was found for any particular model. We concluded that (i) females have a lower survival rate than males, probably due to their larger home ranges, which increase the risk of mortality; (ii) the survival rates of both sexes were lower during the non-breeding period; and (iii) the causes of mortality differed significantly between the two populations, gunshot being the main cause in Seville and electrocution in Murcia.Peer Reviewe

Changes in grassland management and linear infrastructures associated to the decline of an endangered bird population

European grassland birds are experiencing major population declines, mainly due to changes in farmland management. We analyzed the role of habitat availability, grazing management and linear infrastructures (roads and power lines) in explaining spatial and temporal variation in the population density of little bustards (Tetrax tetrax) in Portugal, during a decade in which the species population size halved. We used data from 51 areas (totaling ca. 1,50,000 ha) that were sampled in two different periods (2003–2006 and 2016). In 2003–2006, when the species occurred at high densities, habitat availability was the only factor affecting spatial variation in bustard density. In the 2016 survey, variation in density was explained by habitat availability and livestock management, with reduced bird numbers in areas with higher proportions of cattle. Population declines across the study period were steeper in areas that initially held higher densities of bustards and in areas with a higher proportion of cattle in the total stocking rate. Areas with higher densities of power lines also registered greater density declines, probably due to avoidance behavior and to increased mortality. Overall, our results show little bustards are currently lacking high quality grassland habitat, whose persistence depends on extensive grazing regimes and low linear infrastructure densitiesinfo:eu-repo/semantics/publishedVersio

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.This work was supported by grants from Ministerio de Ciencia e Innovación, Programa Retos-Colaboración RTC2019-007125-1 (for Jorge Simon and Maria Luz Martinez-Chantar); Ministerio de Economía, Industria y Competitividad, Retos a la Sociedad AGL2017- 86927R (for F.M.); Instituto de Salud Carlos III, Proyectos de Investigación en Salud DTS20/00138 and DTS21/00094 (for Jorge Simon and Maria Luz Martinez-Chantar, and Asis Palazon. respectively); Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-founded by European Regional Development Fund/European Social Fund, “Investing in your future” PI19/00819, “Una manera de hacer Europa” FIS PI20/00765, and PI21/01067 (for Jose J. G. Marin., Pau Sancho-Bru,. and Mario F. Fraga respectively); Departamento de Industria del Gobierno Vasco (for Maria Luz Martinez-Chantar); Asturias Government (PCTI) co-funding 2018-2023/ FEDER IDI/2021/000077 (for Mario F. Fraga.); Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00, CEX2021-001136-S PID2020-117941RB-I00, PID2020-11827RB-I00 and PID2019-107956RA-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (for Maria Luz Martinez-Chantar, Francisco J Cubero., Yulia A Nevzorova and Asis Palazon); Ayudas Ramón y Cajal de la Agencia Estatal de Investigación RY2013-13666 and RYC2018- 024183-I (for Leticia Abecia and Asis Palazon); European Research Council Starting Grant 804236 NEXTGEN-IO (for Asis Palazon); The German Research Foundation SFB/TRR57/P04, SFB1382-403224013/ A02 and DFG NE 2128/2-1 (for Francisco J Cubero and Yulia A Nevzorova); National Institute of Health (NIH)/National Institute of Alcohol Abuse and Alcoholism (NIAAA) 1U01AA026972-01 (For Pau Sancho-Bru); Junta de Castilla y León SA074P20 (for Jose J. G. Marin); Junta de Andalucía, Grupo PAIDI BIO311 (for Franz Martin); CIBERER Acciones Cooperativas y Complementarias Intramurales ACCI20-35 (for Mario F. Fraga); Ministerio de Educación, Cultura y Deporte FPU17/04992 (for Silvia Ariño); Fundació Marato TV3 201916-31 (for Jose J. G. Marin.); Ainize Pena-Cearra is a fellow of the University of the Basque Country (UPV/ EHU); BIOEF (Basque Foundation for Innovation and Health Research); Asociación Española contra el Cáncer (Maria Luz Martinez-Chantar and Teresa C. Delgado.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (for Maria Luz Martinez-Chantar); La Caixa Foundation Program (for Maria Luz Martinez-Chantar); Proyecto Desarrollo Tecnologico CIBERehd (for Maria Luz Martinez-Chantar); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III.S