Sharing Jesus with Muslims: A Survey of Church Leaders in Africa

A web survey of 34 pastors and other church leaders in 2020 who had met during graduate studies at Africa International University (AIU) was conducted to understand what is being done in Muslim evangelism in their home churches, primarily in East Africa. They generally characterized Muslims positively, as being made in the image of God, and as needing salvation through Jesus. They identified what they considered to be key differences between Muslims and Christians. Half of their churches made general evangelistic efforts, but most of these made no specific attempt to share the gospel with Muslims. Sharing the gospel with Muslims presents different challenges than sharing the gospel with people of other faiths. Their church members need a deeper understanding of the basic doctrines of the Trinity and salvation through Christ, along with training and tools on how to present the gospel to Muslims in a way they can hear, understand, and accept

Frustration - how it can be measured

A misfit parameter is used to characterize the degree of frustration of ordered and disordered systems. It measures the increase of the ground-state energy due to frustration in comparison with that of a relevant reference state. The misfit parameter is calculated for various spin-glass models. It allows one to compare these models with each other. The extension of this concept to other combinatorial optimization problems with frustration, e.g. p-state Potts glasses, graph-partitioning problems and coloring problems is given.Comment: 10 pages, 1 table, no figures, uses revtex.st

Monitoring snow depth change across a range of landscapes with ephemeral snowpacks using structure from motion applied to lightweight unmanned aerial vehicle videos

Differencing of digital surface models derived from structure from motion (SfM) processing of airborne imagery has been used to produce snow depth (SD) maps with between  ∼ 2 and  ∼ 15&thinsp;cm horizontal resolution and accuracies of ±10&thinsp;cm over relatively flat surfaces with little or no vegetation and over alpine regions. This study builds on these findings by testing two hypotheses across a broader range of conditions: (i) that the vertical accuracy of SfM processing of imagery acquired by commercial low-cost unmanned aerial vehicle (UAV) systems can be adequately modelled using conventional photogrammetric theory and (ii) that SD change can be more accurately estimated by differencing snow-covered elevation surfaces rather than differencing a snow-covered and snow-free surface. A total of 71 UAV missions were flown over five sites, ranging from short grass to a regenerating forest, with ephemeral snowpacks. Point cloud geolocation performance agreed with photogrammetric theory that predicts uncertainty is proportional to UAV altitude and linearly related to horizontal uncertainty. The root-mean-square difference (RMSD) over the observation period, in comparison to the average of in situ measurements along  ∼ 50&thinsp;m transects, ranged from 1.58 to 10.56&thinsp;cm for weekly SD and from 2.54 to 8.68&thinsp;cm for weekly SD change. RMSD was not related to microtopography as quantified by the snow-free surface roughness. SD change uncertainty was unrelated to vegetation cover but was dominated by outliers corresponding to rapid in situ melt or onset; the median absolute difference of SD change ranged from 0.65 to 2.71&thinsp;cm. These results indicate that the accuracy of UAV-based estimates of weekly snow depth change was, excepting conditions with deep fresh snow, substantially better than for snow depth and was comparable to in situ methods.</p

Three-dimensional effects on extended states in disordered models of polymers

We study electronic transport properties of disordered polymers in the presence of both uncorrelated and short-range correlated impurities. In our procedure, the actual physical potential acting upon the electrons is replaced by a set of nonlocal separable potentials, leading to a Schr\"odinger equation that is exactly solvable in the momentum representation. We then show that the reflection coefficient of a pair of impurities placed at neighboring sites (dimer defect) vanishes for a particular resonant energy. When there is a finite number of such defects randomly distributed over the whole lattice, we find that the transmission coefficient is almost unity for states close to the resonant energy, and that those states present a very large localization length. Multifractal analysis techniques applied to very long systems demonstrate that these states are truly extended in the thermodynamic limit. These results reinforce the possibility to verify experimentally theoretical predictions about absence of localization in quasi-one-dimensional disordered systems.Comment: 16 pages, REVTeX 3.0, 5 figures on request from FDA ([email protected]). Submitted to Phys. Rev. B. MA/UC3M/09/9

Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression

The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In this study, we have applied Analytical Multi-scale Identification of Recurring Events analysis and transcript quantification in the TNBC genome across 222 TNBC tumors and identified 138 candidate genes with positive correlation in copy number gain (CNG) and gene expression. siRNA-based loss-of-function screen of the candidate genes has validated EGFR, MYC, ASAP1, IRF2BP2, and CCT5 genes as drivers promoting proliferation in different TNBC cells. MYC, ASAP1, IRF2BP2, and CCT5 display frequent CNG and concurrent expression over 2173 breast cancer tumors (cBioPortal dataset). More frequently are MYC and ASAP1 amplified in TNBC tumors (>30%, n = 320). In particular, high expression of ASAP1, the ADP-ribosylation factor GTPase-activating protein, is significantly related to poor metastatic relapse-free survival of TNBC patients (n = 257, bc-GenExMiner). Furthermore, we have revealed that silencing of ASAP1 modulates numerous cytokine and apoptosis signaling components, such as IL1B, TRAF1, AIFM2, and MAP3K11 that are clinically relevant to survival outcomes of TNBC patients. ASAP1 has been reported to promote invasion and metastasis in various cancer cells. Our findings that ASAP1 is an amplification-dependent TNBC driver gene promoting TNBC cell proliferation, functioning upstream apoptosis components, and correlating to clinical outcomes of TNBC patients, support ASAP1 as a potential actionable target for TNBC treatment

Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression

The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In this study, we have applied Analytical Multi-scale Identification of Recurring Events analysis and transcript quantification in the TNBC genome across 222 TNBC tumors and identified 138 candidate genes with positive correlation in copy number gain (CNG) and gene expression. siRNA-based loss-of-function screen of the candidate genes has validated EGFR, MYC, ASAP1, IRF2BP2, and CCT5 genes as drivers promoting proliferation in different TNBC cells. MYC, ASAP1, IRF2BP2, and CCT5 display frequent CNG and concurrent expression over 2173 breast cancer tumors (cBioPortal dataset). More frequently are MYC and ASAP1 amplified in TNBC tumors (>30%, n = 320). In particular, high expression of ASAP1, the ADP-ribosylation factor GTPase-activating protein, is significantly related to poor metastatic relapse-free survival of TNBC patients (n = 257, bc-GenExMiner). Furthermore, we have revealed that silencing of ASAP1 modulates numerous cytokine and apoptosis signaling components, such as IL1B, TRAF1, AIFM2, and MAP3K11 that are clinically relevant to survival outcomes of TNBC patients. ASAP1 has been reported to promote invasion and metastasis in various cancer cells. Our findings that ASAP1 is an amplification-dependent TNBC driver gene promoting TNBC cell proliferation, functioning upstream apoptosis components, and correlating to clinical outcomes of TNBC patients, support ASAP1 as a potential actionable target for TNBC treatment.Toxicolog

Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP &lt; 0.15). RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, $\textit{cis}$-acting variants represent an important source of phenotypic variation. Consequently, $\textit{cis}$-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, $\textit{P}$ = 5.6x10$^{-6}$). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, $\textit{HELQ}$, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, $\textit{MRPS18C}$ encoding the Mitochondrial Ribosomal Protein S18C and $\textit{FAM175A (ABRAXAS)}$, encoding a $\textit{BRCA1}$ BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with $\textit{HELQ }$ ($\textit{P}$ = 8.28x10$^{-14}$), $\textit{MRPS18C}$ ($\textit{P}$ = 1.94x10$^{-27}$) and $\textit{FAM175A }$ ($\textit{P}$ = 3.83x10$^{-3}$), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.Information regarding funding can be found in the published article or the publisher's website. Funders include Cancer Research UK and the National Institute for Health Research

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis