Archaeology of Atafu, Tokelau: Some initial results from 2008

Surface survey, shovel testing, and stratigraphic excavations were done on Atafu Atoll in Tokelau during August 2008. Initial results suggest that Fale Islet has the most potential for further archaeological research. Dense cultural deposits on this islet are >1 m (39 in.) deep. Cultural material recovered includes food bone, fire-affected volcanic rock, tool-grade basalt flakes and tool fragments, Tridacna shell adzes, and pearl-shell fishhook fragments. Dog bone occurs from the earliest deposits through to the late prehistoric, while pig bone is found only in historic contexts. Fish bone is common throughout, and, with the exception of Tridacna, there are few edible mollusk remains. Initial EDXRF (Energy Dispersive X-Ray Fluorescence) analyses have found the basalt to be consistent with documented sources on Tutuila, Samoa. Basal radiocarbon dates from two excavation units are 660-540 cal. BP and 500-310 cal. BP (at 2σ)

Scrum for product innovation : a longitudinal embedded case study

This article describes the innovation processes used in a partnership between Add Latent Ltd., an asset integrity and maintenance management consulting services provider in the energy sector and University of Salford. The challenge faced by the company is to make their in-house expertise more readily available to a worldwide audience. A longitudinal embedded case study has been used to investigate how installable desktop software applications have been redesigned to create a new set of cloud hosted software services. The innovation team adapted an agile scrum process to include exploratory prototyping and manage the geographical distribution of the team members. A minimum viable product was developed that integrated functional elements of previous software tools into an end-to-end data collection, analysis and visualisation product called AimHi which uses a cloud-hosted web services approach. Field trials were conducted using the software at the Uniper, Isle of Grain power station in Kent, UK. Enhancements were made to the AimHi product which was adopted for use at the Uniper site. The product emerged from a Knwledge Transfer Partnership whci was evaluated on cmplettion by InnovateUK and awarded the highest possible “outstanding” grade. The article illustrates how the scrum software development method was tailored for a product innovation context. Extended periods of evaluation and reflection, prototyping and requirement refinement were combined with periods of incremental feature development using sprints. The AimHi product emerged from a technology transfer and innovation project that has successfully reconciled conflicting demands from customers, universities, partner companies and project staff members

The Grizzly, February 29, 2024

Dr. Harold Dean Trulear Talks Theology and Mass Incarceration • Newly Created Performing and Visual Arts Design and Technology Major • Ursinus Crossword Puzzle • Reimagine Ursinus-Collegeville: Planting a Seed of Change • Spring at Ursinus College Word Search • Meme Corner • Taco Tuesday! • UCWB Playoff Run Comes to an End in Baltimore • Pool Party at Gettysburg! Bears Accept Invitationhttps://digitalcommons.ursinus.edu/grizzlynews/2028/thumbnail.jp

Combining Radiotherapy With Anti-angiogenic Therapy and Immunotherapy; A Therapeutic Triad for Cancer?

Radiotherapy has been used for the treatment of cancer for over a century. Throughout this period, the therapeutic benefit of radiotherapy has continuously progressed due to technical developments and increased insight in the biological mechanisms underlying the cellular responses to irradiation. In order to further improve radiotherapy efficacy, there is a mounting interest in combining radiotherapy with other forms of therapy such as anti-angiogenic therapy or immunotherapy. These strategies provide different opportunities and challenges, especially with regard to dose scheduling and timing. Addressing these issues requires insight in the interaction between the different treatment modalities. In the current review, we describe the basic principles of the effects of radiotherapy on tumor vascularization and tumor immunity and vice versa. We discuss the main strategies to combine these treatment modalities and the hurdles that have to be overcome in order to maximize therapeutic effectivity. Finally, we evaluate the outstanding questions and present future prospects of a therapeutic triad for cancer

Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas

The Epstein-Barr virus (EBV)-positive subtype of gastric adenocarcinoma is conventionally identified by in situ hybridization (ISH) for viral nucleic acids, but next-generation sequencing represents a potential alternative. We therefore determined normalized EBV read counts by whole genome, whole exome, mRNA and miRNA sequencing for 295 fresh-frozen gastric tumor samples. Formalin-fixed, paraffin-embedded tissue sections were retrieved for ISH confirmation of 13 high-EBV and 11 low-EBV cases. In pairwise comparisons, individual samples were either concordantly high or concordantly low by all genomic methods for which data were available. Empiric cut-offs of sequencing counts identified 26 (9%) tumors as EBV-positive. EBV-positivity or negativity by molecular testing was confirmed by EBER-ISH in all but one tumor evaluated by both approaches (kappa=0.91). EBV-positive gastric tumors may be accurately identified by quantifying viral sequences in genomic data. Simultaneous analyses of human and viral DNA, mRNA and miRNA could streamline tumor profiling for clinical care and research

Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer

OBJECTIVE: Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse gastric cancer (DGC) histological subtype. Among these alterations are interchromosomal translations leading to the fusion of the adhesion protein CLDN18 and RHO regulator ARHGAP26. It remains unclear how these fusion constructs impact the activity of the RHO pathway and what is their broader impact on gastric cancer development. Herein, we developed a model to allow us to study the function of this fusion protein in the pathogenesis of DGC and to identify potential therapeutic targets for DGC tumours with these alterations. DESIGN: We built a transgenic mouse model with LSL-CLDN18-ARHGAP26 fusion engineered into the Col1A1 locus where its expression can be induced by Cre recombinase. Using organoids generated from this model, we evaluated its oncogenic activity and the biochemical effects of the fusion protein on the RHOA pathway and its downstream cell biological effects in the pathogenesis of DGC. RESULTS: We demonstrated that induction of CLDN18-ARHGAP26 expression in gastric organoids induced the formation of signet ring cells, characteristic features of DGC and was able to cooperatively transform gastric cells when combined with the loss of the tumour suppressor geneTrp53. CLDN18-ARHGAP26 promotes the activation of RHOA and downstream effector signalling. Molecularly, the fusion promotes activation of the focal adhesion kinase (FAK) and induction of the YAP pathway. A combination of FAK and YAP/TEAD inhibition can significantly block tumour growth. CONCLUSION: These results indicate that the CLDN18-ARHGAP26 fusion is a gain-of-function DGC oncogene that leads to activation of RHOA and activation of FAK and YAP signalling. These results argue for further evaluation of emerging FAK and YAP-TEAD inhibitors for these deadly cancers

Sox2 Suppresses Gastric Tumorigenesis in Mice

SummarySox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. By using ChIP-seq analysis, we have found that the majority of Sox2 targets in gastric epithelial cells are tissue specific and related to functions such as endoderm development, Wnt signaling, and gastric cancer. Unexpectedly, we found that Sox2 itself is dispensable for gastric stem cell and epithelial self-renewal, yet Sox2+ cells are highly susceptible to tumorigenesis in an Apc/Wnt-driven mouse model. Moreover, Sox2 loss enhances, rather than impairs, tumor formation in Apc-deficient gastric cells in vivo and in vitro by inducing Tcf/Lef-dependent transcription and upregulating intestinal metaplasia-associated genes, providing a mechanistic basis for the observed phenotype. Together, these data identify Sox2 as a context-dependent tumor suppressor protein that is dispensable for normal tissue regeneration but restrains stomach adenoma formation through modulation of Wnt-responsive and intestinal genes

Energy Dependence of the Near-Threshold Total Cross-Section for the pp --> pp eta' Reaction

Total cross sections for the pp --> pp eta' reaction have been measured in the excess energy range from Q = 1.53 MeV to Q = 23.64 MeV. The experiment has been performed at the internal installation COSY-11 using a stochastically cooled proton beam of the COoler SYnchrotron COSY and a hydrogen cluster target. The determined energy dependence of the total cross section weakens the hypothesis of the S-wave repulsive interaction between the eta' meson and the proton. New data agree well with predictions based on the phase-space distribution modified by the proton-proton final-state-interaction (FSI) only.Comment: 12 pages, 1 table, 4 figure

Multiscale mapping of plant functional groups and plant traits in the High Arctic using field spectroscopy, UAV imagery and Sentinel-2A data

The Arctic is warming twice as fast as the rest of the planet, leading to rapid changes in species composition and plant functional trait variation. Landscape-level maps of vegetation composition and trait distributions are required to expand spatially-limited plot studies, overcome sampling biases associated with the most accessible research areas, and create baselines from which to monitor environmental change. Unmanned aerial vehicles (UAVs) have emerged as a low-cost method to generate high-resolution imagery and bridge the gap between fine-scale field studies and lower resolution satellite analyses. Here we used field spectroscopy data (400-2500 nm) and UAV multispectral imagery to test spectral methods of species identification and plant water and chemistry retrieval near Longyearbyen, Svalbard. Using the field spectroscopy data and Random Forest analysis, we were able to distinguish eight common High Arctic plant tundra species with 74% accuracy. Using partial least squares regression (PLSR), we were able to predict corresponding water, nitrogen, phosphorus and C:N values (r (2) = 0.61-0.88, RMSEmean = 12%-64%). We developed analogous models using UAV imagery (five bands: Blue, Green, Red, Red Edge and Near-Infrared) and scaled up the results across a 450 m long nutrient gradient located underneath a seabird colony. At the UAV level, we were able to map three plant functional groups (mosses, graminoids and dwarf shrubs) at 72% accuracy and generate maps of plant chemistry. Our maps show a clear marine-derived fertility gradient, mediated by geomorphology. We used the UAV results to explore two methods of upscaling plant water content to the wider landscape using Sentinel-2A imagery. Our results are pertinent for high resolution, low-cost mapping of the Arctic.Peer reviewe

Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review

Background: KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear. Methods: We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse’s Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI. Results: KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.29-2.26 for codon 61 mutation; colorectal cancer-specific mortality HR = 0.86, 95% CI = 0.42-1.78 for codon 146 mutation]. Conclusions: Tumors with KRAS mutations in codons 61 and 146 account for an appreciable proportion (approximately 5%) of colorectal cancers, and their clinicopathological and molecular features appear generally similar to KRAS codon 12 or 13 mutated cancers. To further assess clinical utility of KRAS codon 61 and 146 testing, large-scale trials are warranted