Imperfect Correlation Research Articles

Estimation of the Harvey Bradshaw Index from the Patient-Reported Outcome 2 in Crohn's Disease: Results Based on a Large Scale Randomized Controlled Trial.

Many registrational trials in Crohn's disease assess treatment efficacy with the 2-item Patient-Reported Outcome (PRO2), while the Harvey-Bradshaw Index (HBI) is prominent in pragmatic trials and clinical practice. The translation between PRO2 and HBI has not been established. Data from a Phase 3 trial of vedolizumab in Crohn's disease were used to determine the Pearson correlation between PRO2 and HBI. Linear regression was used to fit equations that estimate between indices; 95% prediction intervals were determined for HBI scores corresponding to PRO2 thresholds for disease activity. Internal validation of the conversion equations was performed using the bootstrap methods. PRO2 and HBI were highly correlated at baseline (r = 0.75 95% confidence interval (CI) 0.73-0.78; P < .001), induction (r = 0.87; 95% CI, 0.85-0.88; P < .001), and maintenance (r = 0.88; 95% CI, 0.85-0.90; P < .001). PRO2 and HBI change scores were moderately correlated (r = 0.72; 95% CI 0.69-0.75; P < .001) in induction and more strongly correlated during maintenance (r = 0.81; 95% CI 0.78- 0.84; P < .001). Regression equations for conversion of PRO2 to HBI from all cohorts (induction, maintenance, randomized, open-label) support an approximate conversion where HBI = 0.5 PRO2. As expected from the imperfect correlation between scores, the prediction intervals were generally wide. No evidence of overfitting was seen in bootstrap internal validation. PRO2and HBI correlate strongly and conversion between them is possible. These findings facilitate the practical application of trial results and clinical guidelines.

GCN-MHSA: A novel malicious traffic detection method based on graph convolutional neural network and multi-head self-attention mechanism

With the increasing size and complexity of network, network traffic becomes more and more correlated with each other, and the traditional manner of presenting network traffic in a Euclidean structure is difficult to effectively capture the correlation information of network traffic. In contrast, graph structured data has gained much attention in recent years due to its ability to represent the correlation between different traffic flows; In addition, models and algorithms related to Graph Convolution Neural network (GCN) have been used for malicious traffic detection. However, existing GCN-based malicious traffic detection methods still suffer from incomplete description of the flow-level features of network traffic, imperfect traffic correlation establishment mechanism and failure to distinguish the importance of features during model training. Based on this, this study proposes a malicious traffic detection method called GCN-MHSA based on Graph Convolutional Neural network and Multi-Head Self-Attention mechanism. Firstly, the flow-level features of network traffic are populated and more information close to the features are selected to describe the network traffic; And then, the link homogeneity is used to establish the correlations between network traffic; Moreover, multi-head self-attention mechanism is introduced in the GCN model to provide larger weight to important features; Finally, an improved GCN is used as a deep learning model to detect malicious traffic. Extensive experimental results on three publicly available network traffic datasets and a real network traffic dataset show that the proposed GCN-MHSA method performs better than five baselines in terms of detection effect and stability, with an improvement of about 2.4% in accuracy, recall and F1-measure as well as an improvement of about 2.1% in precision.

The right to reasonable inferences in automated decision systems as an unfolding of the fundamental right to the protection of personal data in Brazil and beyond

ABSTRACT This paper proposes expanding personal data protection by recognizing the right to reasonable inferences derived from the fundamental right to data protection and the principle of free development of personality. Automated systems using predictive algorithms and correlations based on profiles can have negative consequences, particularly discrimination from generalization or inadequate correlation. These systems often fail to consider individual uniqueness. The article highlights that imperfect correlations in automated systems threaten individual rights by undermining the free development of personality and informational selfdetermination. Recognizing the right to reasonable inferences strengthens data protection's objective dimension, crucial for safeguarding against discriminatory inferences. It also requires data controllers to justify implementing such systems. To achieve this, the study suggests interpreting the Brazilian Data Protection Law no. 13.079/2018, known as ‘LGPD’, to position the right to reasonable inferences as a behavioral guideline for data controllers. This interpretation emphasizes transparency, understandability, and accountability. Recognizing this right aims to promote adherence to the principle of responsibility and ensure the necessary transparency to address and manage negative consequences.

Establishment of two serological methods for detecting IgG and neutralizing antibodies against Crimean-Congo hemorrhagic fever virus glycoprotein.

The Crimean-Congo hemorrhagic fever virus (CCHFV), the most geographically widespread tick-borne virus, is endemic in Africa, Eastern Europe and Asia, with infection resulting in mortality in up to 30% of cases. Currently, there are no approved vaccines or effective therapies available for CCHF. The CCHFV should only be manipulated in the BSL-4 laboratory, which has severely hampered basic seroprevalence studies. In the present study, two antibody detection methods in the forms of an enzyme-linked immunosorbent assay (ELISA) and a surrogate virus neutralization test (sPVNT) were developed using a recombinant glycoprotein (rGP) and a vesicular stomatitis virus (VSV)-based virus bearing the CCHFV recombinant glycoprotein (rVSV/CCHFV) in a biosafety level 2 (BSL-2) laboratory, respectively. The rGP-based ELISA and rVSV/CCHFV-based sVNT were established by using the anti-CCHFV pre-GC mAb 11E7, known as a broadly cross-reactive, potently neutralizing antibody, and their applications as diagnostic antigens were validated for the specific detection of CCHFV IgG and neutralizing antibodies in experimental animals. In two tests, mAb clone 11E7 (diluted at 1:163840 or 512) still displayed positive binding and neutralization, and the presence of antibodies (IgG and neutralizing) against the rGP and rVSV/CCHFV was also determined in the sera from the experimental animals. Both mAb 11E7 and animal sera showed a high reactivity to both antigens, indicating that bacterially expressed rGP and rVSV/CCHFV have good immunoreactivity. Apart from establishing two serological testing methods, their results also demonstrated an imperfect correlation between IgG and neutralizing antibodies. Within this limited number of samples, the rGP and rVSV/CCHFV could be safe and convenient tools with significant potential for research on specific antibodies and serological samples.

Spatial 3D correlation of flux pinning with porosity distribution in YBa2Cu3O7−δ using tensorial neutron tomography

Engineering devices from High Temperature Superconductors (HTS) for practical applications such as in transport and medical imaging requires an understanding of their critical current density (JC) distribution and how the material properties affect this. JC describes the maximum gradient of flux that can be found in a superconductor sustained by vortex pinning which is the preferential positioning of vortex in defective regions of weaker superconductivity. Local correlation of imperfections with high pinning has required destructive methods such as slicing then scanning with local magnetic probes. We describe the first case of non-destructive spatial correlation of flux pinning and consequently JC with bulk imperfections at different temperatures in top-seeded melt grown (TSMG) YBa2Cu3O7−δ chosen for its high pinning in addition to a rich structure of pores, twins and grain boundaries. This is facilitated by a combination of polarized neutron tomography to image trapped magnetic fields in a range around the material critical temperature and conventional neutron tomography to characterize potential pinning objects. The results indicate that there is indeed preferential trapping in the porous regions independent of the resolvable pore size. Polarized optical microscopy data suggests that the observed phenomenon is attributable to twin boundaries and crack defects located at the pore interface.

A High-Resolution Imaging Method for Multiple-Input Multiple-Output Sonar Based on Deterministic Compressed Sensing.

Differences between conventional sonar and Multiple-Input Multiple-Output (MIMO) sonar systems arise in achieving high angular and range resolution. MIMO sonar uses Matched Filtering (MF) with well-correlated transmitted signals to enhance spatial resolution by obtaining virtual arrays. However, imperfect correlation characteristics yield high sidelobe values, which hinder accurate target localization in underwater imagery. To address this, a Compressed Sensing (CS) method is proposed by reconstructing echo signals to suppress correlation noise between orthogonal waveforms. A shifted dictionary matrix and a deterministic Discrete Fourier Transform (DFT) measurement matrix are used to multiply received echo signals to yield compressed measurements. A sparse recovery algorithm is applied to optimize signal reconstruction before joint transmit-receive beamforming forms a 2D sonar image in the angle-range domain. Numerical simulations and lake experimental results confirm the effectiveness of the proposed method, by obtaining a lower sidelobe sonar image under sub-Nyquist sampling rates as compared with other approaches.

Qualification of major pathological response as a surrogate endpoint for relapse-free survival following neoadjuvant immunotherapy for hepatocellular carcinoma.

506 Background: Neoadjuvant use of immune checkpoint inhibitors (ICI) is feasible and achieves pathological responses in a subset of patients with hepatocellular carcinoma (HCC). However, it is not clear whether pathological response to ICI translates into long-term survival benefit. Methods: We analysed patient-level data from 86 subjects recruited to 4 prospective phase I/II clinical trials of ICI prior to liver resection (LR) in 9 centres in the United States, Europe, and Asia and included a cohort of 23 patients (pts) receiving neoadjuvant ICI off trial. Radiological response was assessed with RECISTv1.1. Major (MPR) and complete pathological response (pCR) were considered as ≥70% and 100% non-viable tumour in the resected specimen, respectively. Pathological responses were correlated with radiologic overall response rates (ORR) and relapse-free survival (RFS). Results: Out of 109 pts treated between 10/2017 and 09/2023, 55 pts (50.5%) received a double ICI combination, 35 (32.1%) ICI monotherapy, and 19 (17.4%) an antiangiogenic/ICI combination. In 19 pts (17.4%) an adjuvant ICI course was administered for a median time of 5.5 months (m) (interquartile range [IQR] 3.7-6.0). Most of pts were male (77.6%) with underlying viral chronic liver disease (68.2%), performance status 0 (83.5%), BCLC 0-A (55%), a median tumour diameter of 6.0 cm (IQR 3.9-9.9) without portal vein thrombosis (75.7%). After a median follow-up of 27.3 m (95% CI 21.5-33.0), 35 (32.1%) relapses and 14 (12.8%) deaths occurred. Radiologic ORR was 28.5% (n=31), with 3.7% complete responses (CR, n=4) and 24.8% partial responses (PR, n=27). Out of 100 pts evaluable for a pathological response, 33% achieved MPR and 19% pCR. MPR was more likely in patients who had achieved a radiologic PR or CR (82%) as compared to those who did not (14% p&lt;0.001), however linear correlation suggested an imperfect correlation between ORR and MPR (R2 0.43, p&lt;0.0001). Median RFS was 43.5m (95%CI, 27.5-59.6), while median overall survival was not reached (NR). mRFS was significantly improved in pts with MPR (NR vs 28.3m [95%CI, 13.1-43.5], hazard ratio [HR] 0.27 [95%CI, 0.11-0.69], p = 0.003) and with pCR (NR vs 32.8m [95%CI, 15.2-50.4], HR 0.20 [95%CI, 0.05-0.82], p=0.013). Conclusions: This study is the first to qualify the role of MPR as a putative surrogate endpoint for recurrence-free survival in pts treated with neoadjuvant immunotherapy for HCC. Validation in larger phase III clinical trials is warranted.

Local Oxidation States in {FeNO}6-8 Porphyrins: Insights from DMRG/CASSCF-CASPT2 Calculations.

A first DMRG/CASSCF-CASPT2 study of a series of paradigmatic {FeNO}6, {FeNO}7, and {FeNO}8 heme-nitrosyl complexes has led to substantial new insight as well as uncovered key shortcomings of the DFT approach. By virtue of its balanced treatment of static and dynamic correlation, the calculations have provided some of the most authoritative information available to date on the energetics of low- versus high-spin states of different classes of heme-nitrosyl complexes. Thus, the calculations indicate low doublet-quartet gaps of 1-4 kcal/mol for {FeNO}7 complexes and high singlet-triplet gaps of ≳20 kcal/mol for both {FeNO}6 and {FeNO}8 complexes. In contrast, DFT calculations yield widely divergent spin state gaps as a function of the exchange-correlation functional. DMRG-CASSCF calculations also help calibrate DFT spin densities for {FeNO}7 complexes, pointing to those obtained from classic pure functionals as the most accurate. The general picture appears to be that nearly all the spin density of Fe[P](NO) is localized on the Fe, while the axial ligand imidazole (ImH) in Fe[P](NO)(ImH) pushes a part of the spin density onto the NO moiety. An analysis of the DMRG-CASSCF wave function in terms of localized orbitals and of the resulting configuration state functions in terms of resonance forms with varying NO(π*) occupancies has allowed us to address the longstanding question of local oxidation states in heme-nitrosyl complexes. The analysis indicates NO(neutral) resonance forms [i.e., Fe(II)-NO0 and Fe(III)-NO0] as the major contributors to both {FeNO}6 and {FeNO}7 complexes. This finding is at variance with the common formulation of {FeNO}6 hemes as Fe(II)-NO+ species but is consonant with an Fe L-edge XAS analysis by Solomon and co-workers. For the {FeNO}8 complex {Fe[P](NO)}-, our analysis suggests a resonance hybrid description: Fe(I)-NO0 ↔ Fe(II)-NO-, in agreement with earlier DFT studies. Vibrational analyses of the compounds studied indicate an imperfect but fair correlation between the NO stretching frequency and NO(π*) occupancy, highlighting the usefulness of vibrational data as a preliminary indicator of the NO oxidation state.

Symbiotic Backscatter Communication Underlying a Cell-Free Massive MIMO System

In ambient backscatter communications, backscatter devices (BDs) utilize ambient “legacy” radio signals as both a harvested energy source and a carrier on which to modulate data. Symbiotic radio, a subtype in which the legacy system assists both its own users and underlaid BDs, has attracted much research interest recently. Furthermore, cell-free massive multiple-input multiple-output (CF mMIMO) systems are promising for beyond-5G networks from both spectral and energy efficiency perspectives. To reap the benefits of both, we consider a primary CF mMIMO system where the access points (APs) aid an underlaid BD layer to both harvest energy and reflect information toward the primary receivers (which receive data from both layers). To acquire separate channel state information (CSI) of the direct and backscattered channels at the APs, a two-phase uplink pilot training method is proposed, with the effects of pilot contamination and spatial correlation between antennas accounted for. However, the receivers are assumed to only have partial CSI (statistical knowledge plus instantaneous phase information for partially-coherent reception). Assuming uplink/downlink radio channel reciprocity, the CSI is used to design downlink precoding vectors for the APs such that channel hardening is enhanced and both primary receivers and BDs benefit. We derive expressions for the average signal-to-interference-plus-noise ratios of both primary and backscatter signals, accounting for the effects of imperfect CSI, spatial correlation, pilot contamination, and channel hardening. Furthermore, the average power harvested in the BDs is derived. Simulation results demonstrate that the performance of the proposed scheme is much more uniform across all devices with CF mMIMO than with conventional co-located mMIMO. The use of CF mMIMO also largely removes the need for special consideration of the BD layer in the symbiotic system, which is not the case with co-located mMIMO.

On the Diversification Effect in Solvency II for Extremely Dependent Risks

In this article, we investigate the validity of diversification effect under extreme-value copulas, when the marginal risks of the portfolio are identically distributed, which can be any one having a finite endpoint or belonging to one of the three maximum domains of attraction. We show that Value-at-Risk (V@R) under extreme-value copulas is asymptotically subadditive for marginal risks with finite mean, while it is asymptotically superadditive for risks with infinite mean. Our major findings enrich and supplement the context of the second fundamental theorem of quantitative risk management in existing literature, which states that V@R of a portfolio is typically non-subadditive for non-elliptically distributed risk vectors. In particular, we now pin down when the V@R is super or subadditive depending on the heaviness of the marginal tail risk. According to our results, one can take advantages from the diversification effect for marginal risks with finite mean. This justifies the standard formula for calculating the capital requirement under Solvency II in which imperfect correlations are used for various risk exposures.

Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma

BackgroundThe need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past,...

GATA2 Deficiency: Predisposition to Myeloid Malignancy and Hematopoietic Cell Transplantation.

GATA2 deficiency is a haploinsufficiency syndrome associated with a wide spectrum of disease, including severe monocytopenia and B and NK lymphopenia, predisposition to myeloid malignancies, human papillomavirus infections, and infections with opportunistic organisms, particularly nontuberculous mycobacteria, herpes virus, and certain fungi. GATA2 mutations have variable penetrance and expressivity with imperfect genotype-phenotype correlations. However, approximately 75% of patients will develop a myeloid neoplasm at some point. Allogeneic hematopoietic cell transplantation (HCT) is the only currently available curative therapy. Here, we review the clinical manifestations of GATA2 deficiency, characterization of the hematologic abnormalities and progression to myeloid malignancy, and current HCT practices and outcomes. Cytogenetic abnormalities are common with high rates of trisomy 8, monosomy 7, and unbalanced translocation der(1;7) and may suggest an underlying GATA2 deficiency in patients presenting with myelodysplastic syndrome (MDS). Mutations in ASXL1 and STAG2 are the most frequently encountered somatic mutations and are associated with lower survival probability. A recent report of 59 patients with GATA2 deficiency who underwent allogenic HCT with myeloablative, busulfan-based conditioning and post-transplant cyclophosphamide reported excellent overall and event-free survival of 85% and 82% with reversal of disease phenotype and low rates of graft versus host disease. Allogeneic HCT with myeloablative conditioning results in disease correction and should be considered for patients with a history of recurrent, disfiguring and/or severe infections, organ dysfunction, MDS with cytogenetic abnormalities, high-risk somatic mutations or transfusion dependence, or myeloid progression. Improved genotype/phenotype correlations are needed to allow for greater predictive capabilities.

Comparison of two molecular barcodes for the study of equine strongylid communities with amplicon sequencing.

Basic knowledge on the biology and epidemiology of equine strongylid species still needs to be improved to contribute to the design of better parasite control strategies. Nemabiome metabarcoding is a convenient tool to quantify and identify species in bulk samples that could overcome the hurdle that cyathostomin morphological identification represents. To date, this approach has relied on the internal transcribed spacer 2 (ITS-2) of the ribosomal RNA gene, with a limited investigation of its predictive performance for cyathostomin communities. Using DNA pools of single cyathostomin worms, this study aimed to provide the first elements to compare performances of the ITS-2 and a cytochrome c oxidase subunit I (COI) barcode newly developed in this study. Barcode predictive abilities were compared across various mock community compositions of two, five and 11 individuals from distinct species. The amplification bias of each barcode was estimated. Results were also compared between various types of biological samples, i.e., eggs, infective larvae or adults. Bioinformatic parameters were chosen to yield the closest representation of the cyathostomin community for each barcode, underscoring the need for communities of known composition for metabarcoding purposes. Overall, the proposed COI barcode was suboptimal relative to the ITS-2 rDNA region, because of PCR amplification biases, reduced sensitivity and higher divergence from the expected community composition. Metabarcoding yielded consistent community composition across the three sample types. However, imperfect correlations were found between relative abundances from infective larvae and other life-stages for Cylicostephanus species using the ITS-2 barcode. While the results remain limited by the considered biological material, they suggest that additional improvements are needed for both the ITS-2 and COI barcodes.

Multi-Omics Profiling of Hypertrophic Cardiomyopathy Reveals Altered Mechanisms in Mitochondrial Dynamics and Excitation-Contraction Coupling.

Hypertrophic cardiomyopathy is one of the most common inherited cardiomyopathies and a leading cause of sudden cardiac death in young adults. Despite profound insights into the genetics, there is imperfect correlation between mutation and clinical prognosis, suggesting complex molecular cascades driving pathogenesis. To investigate this, we performed an integrated quantitative multi-omics (proteomic, phosphoproteomic, and metabolomic) analysis to illuminate the early and direct consequences of mutations in myosin heavy chain in engineered human induced pluripotent stem-cell-derived cardiomyocytes relative to late-stage disease using patient myectomies. We captured hundreds of differential features, which map to distinct molecular mechanisms modulating mitochondrial homeostasis at the earliest stages of pathobiology, as well as stage-specific metabolic and excitation-coupling maladaptation. Collectively, this study fills in gaps from previous studies by expanding knowledge of the initial responses to mutations that protect cells against the early stress prior to contractile dysfunction and overt disease.

Optimal index insurance and basis risk decomposition: an application to Kenya

AbstractIndex insurance is a promising tool to reduce the risk faced by farmers, but high basis risk, which arises from imperfect correlation between the index and individual farm yields, has limited its adoption to date. Improving adoption will require reducing one or both of the two fundamental sources of basis risk: the intrinsic heterogeneity within an insurance zone (zonal risk), and the lack of predictive accuracy of the index (design risk). Previous work has focused mostly on design risk, conflating the quality of the index with the quality of the zone. Consequently, there is currently no way to distinguish a “good index in a bad zone” from a “bad index in a good zone”. Here we investigate the relative roles of zonal and design risk, with two main contributions. First, using a formal decomposition of basis risk, we show that the optimal index is the first principal component of the correlation matrix of yields between fields. This provides a simple upper bound on the insurable basis risk that any index can reach within a given zone. Second, we use 10 m resolution satellite data on maize yields in Kenya to provide the first large‐scale empirical analysis of the extent of zonal versus design risk. Our results show a strong local heterogeneity in yields, underscoring the challenge of implementing index insurance in smallholder systems and the potential benefits of low‐cost yield measurement approaches that can enable more local definitions of insurance zones.

Critical comparison of general-purpose collective variables for crystal nucleation.

The nucleation of crystals is a prominent phenomenon in science and technology that still lacks a full atomic-scale understanding. Much work has been devoted to identifying order parameters able to track the process, from the inception of early nuclei to their maturing to critical size until growth of an extended crystal. We critically assess and compare two powerful distance-based collective variables, an effective entropy derived from liquid state theory and the path variable based on permutation invariant vectors using the Kob-Andersen binary mixture and a combination of enhanced-sampling techniques. Our findings reveal a comparable ability to drive nucleation when a bias potential is applied, and comparable free-energy barriers and structural features. Yet, we also found an imperfect correlation with the committor probability on the barrier top which was bypassed by changing the order parameter definition.

Ichthyosis

The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction leads to increased transepidermal water loss and inflammation. Disordered cornification is clinically characterized by skin scaling with various degrees of thickening, desquamation (peeling) and erythema (redness). Regardless of the type of ichthyosis, many patients suffer from itching, recurrent infections, sweating impairment (hypohidrosis) with heat intolerance, and diverse ocular, hearing and nutritional complications that should be monitored periodically. The characteristic clinical features are considered to be a homeostatic attempt to repair the skin barrier, but heterogeneous clinical presentation and imperfect phenotype-genotype correlation hinder diagnosis. An accurate molecular diagnosis is, however, crucial for predicting prognosis and providing appropriate genetic counselling. Most ichthyoses severely affect patient quality of life and, in severe forms, may cause considerable disability and even death. So far, treatment provides only symptomatic relief. It is lifelong, expensive, time-consuming, and often provides disappointing results. A better understanding of the molecular mechanisms that underlie these conditions is essential for designing pathogenesis-driven and patient-tailored innovative therapeutic solutions.

Molecular Alterations and Putative Therapeutic Targeting of Planar Cell Polarity Proteins in Breast Cancer.

Treatment and outcomes of breast cancer, one of the most prevalent female cancers, have improved in recent decades. However, metastatic breast cancer remains incurable in most cases, and new therapies are needed to ameliorate prognosis. Planar cell polarity (PCP) is a characteristic of epithelial cells that form layers and is integral to the communication of these cells with neighboring cells. Dysfunction of PCP is observed in cancers and may confer a targetable vulnerability. The breast cancer cohorts from The Cancer Genome Atlas (TCGA) and the METABRIC study were interrogated for molecular alterations in genes of the PCP pathway. The groups with the most prevalent alterations were characterized, and survival was compared with counterparts not possessing PCP alterations. Breast cancer cell lines with PCP alterations from the Cancer Cell Line Encyclopedia (CCLE) were interrogated for sensitivity to drugs affecting PCP. Among genes of the PCP pathway, VANGL2, NOS1AP and SCRIB display amplifications in a sizable minority of breast cancers. Concomitant up-regulation at the mRNA level can be observed mostly in basal cancers, but it does not correlate well with the amplification status of the genes, as it can also be observed in non-amplified cases. In an exploration of cell line models, two of the four breast cancer cell line models with amplifications in VANGL2, NOS1AP and SCRIB display sensitivity to drugs inhibiting acyl-transferase porcupine interfering with the WNT pathway. This sensitivity suggests a possible therapeutic role of these inhibitors in cancers bearing the amplifications. Molecular alterations in PCP genes can be observed in breast cancers with a predilection for the basal sub-type. An imperfect correlation of copy number alterations with mRNA expression suggests that post-translational modifications are important in PCP regulation. Inhibitors of acyl-transferase porcupine may be rational candidates for combination therapy development in PCP-altered breast cancers.

ANALYSIS OF DEPOSITIONAL ENVIRONMENTS OF UK FIELD RESERVOIR SANDS IN NIGER DELTA BASIN, NIGERIA

The environments of deposition play a vital role during hydrocarbon formation, migration, trapping and storage. Since the reservoir rocks are a function of their depositional environments, the successful tapping of hydrocarbon from its host rock when wells are drilled depends largely on the petrophysical characteristics of the reservoir rocks which in turn originated from and are influenced by their depositional environment. The reservoir facies in Niger Delta shows a broad range of characteristic sedimentological complexities that gave rise to subsurface geological, drilling and production problems occurring in UK Field. The problems include inaccurate determination of environments of deposition, imperfect stratigraphic correlations and reservoir top uncertainty across the UK Field which are targeted by this research in other to help resolve these challenges facing oil and gas industries in the Niger Delta basin of Nigeria. The research findings will assist in the evaluation of depositional environments and well-to-well lithologic correlation within the UK Field and Niger Delta Basin at large. It will also help to unravel major causes of reservoir top uncertainty in UK Field. Also, it will help in future planning and drilling of new wells within UK Field. The determination of the depositional environments of UK Field reservoir sands were carried out to determine the depositional environment of reservoir sand bodies based on data from seven (7) wells. The determination of depositional environments of sand facies penetrated by wells UK1, UK2, UK3, UK4, UK5, UK6 and UK8 was achieved through a side-by-side comparison of their log suites to standard log motifs. Results of facies analysis showed that the reservoir sands belong to mostly (i) fluvial channel, (ii) barrier bar, (iii) lower-middle shoreface, (iv) distributary mouth bar, (v) distributary channel, (vi) point bar and (vii) tidal channel environments that belonged to parts of a deltaic system. Lithologic correlation result reveals the existence of good correlation among all wells in UK Field due to good geological similarities except well UK8 that failed to correlate perfectly with others thereby establishing the existence of reservoir top uncertainty within UK Field. Therefore, reservoir top uncertainty within UK Field is geologically controlled.

Different proxies, different stories? Imperfect correlations and different determinants of fitness in bighorn sheep.

Measuring individual fitness empirically is required to assess selective pressures and predicts evolutionary changes in nature. There is, however, little consensus on how fitness should be empirically estimated. As fitness proxies vary in their underlying assumptions, their relative sensitivity to individual, environmental, and demographic factors may also vary. Here, using a long-term study, we aimed at identifying the determinants of individual fitness in bighorn sheep (Ovis canadensis) using seven fitness proxies. Specifically, we compared four-lifetime fitness proxies: lifetime breeding success, lifetime reproductive success, individual growth rate, individual contribution to population growth, and three multi-generational proxies: number of granddaughters, individual descendance in the next generation, and relative genetic contribution to the next generation. We found that all proxies were positively correlated, but the magnitude of the correlations varied substantially. Longevity was the main determinant of most fitness proxies. Individual fitness calculated over more than one generation was also affected by population density and growth rate. Because they are affected by contrasting factors, our study suggests that different fitness proxies should not be used interchangeably as they may convey different information about selective pressures and lead to divergent evolutionary predictions. Uncovering the mechanisms underlying variation in individual fitness and improving our ability to predict evolutionary change might require the use of several, rather than one, the proxy of individual fitness.