Interactive Visualization of the Largest Radioastronomy Cubes

3D visualization is an important data analysis and knowledge discovery tool, however, interactive visualization of large 3D astronomical datasets poses a challenge for many existing data visualization packages. We present a solution to interactively visualize larger-than-memory 3D astronomical data cubes by utilizing a heterogeneous cluster of CPUs and GPUs. The system partitions the data volume into smaller sub-volumes that are distributed over the rendering workstations. A GPU-based ray casting volume rendering is performed to generate images for each sub-volume, which are composited to generate the whole volume output, and returned to the user. Datasets including the HI Parkes All Sky Survey (HIPASS - 12 GB) southern sky and the Galactic All Sky Survey (GASS - 26 GB) data cubes were used to demonstrate our framework's performance. The framework can render the GASS data cube with a maximum render time < 0.3 second with 1024 x 1024 pixels output resolution using 3 rendering workstations and 8 GPUs. Our framework will scale to visualize larger datasets, even of Terabyte order, if proper hardware infrastructure is available.Comment: 15 pages, 12 figures, Accepted New Astronomy July 201

Targeted Online Advertisements: Effectiveness as a Function of Need-for-Cognition

Previous research has suggested that targeted online advertising is more effective when users have a preexisting interest in a product or service. While technology now allows marketers to track the demographics and behaviors of potential customers, the current research examines online ad-perception at an individual level, specifically focused on differences in need-for-cognition. Participants were asked to read a short online news article and were randomly assigned to view a webpage containing either gender-neutral or gender-targeted advertisements. While it was predicted that advertisement recall would be stronger for targeted than non-targeted advertisements, no such association was found. Additionally, advertisement recall did not differ for as a function of need-for-cognition. Despite insignificant findings it is important to note that individual differences in the perception of online advertisements may exist, and that marketers should consider these factors when placing advertisements online

Recommendations for Increased Communication and Collaboration between Community-Based Organizations

Through researching CBOs across Washington, Oregon, Northern California, and British Columbia, it is evident that there are need gaps in the organizational capacity in CBOs and other environmental groups for outreach and communication support to collaborate. A dedicated online space where environmental organizations and other conservation-focused groups can share their current projects and identify opportunities for collaboration and capacity building would be beneficial to the community and create a more cohesive resource management strategy. For this capstone project, information was collected from natural resource focused community-based organizations regarding barriers and challenges to collaborating with other organizations, and how might a website most benefit them in their efforts in outreach to other organizations and the public. While the goal of this project is not the completed website, it is the start of a comprehensive collection of data to design a holistic and efficient website that organizations and community members can use to connect and collaborate

HER2-family signalling mechanisms, clinical implications and targeting in breast cancer.

Approximately 20 % of human breast cancers (BC) overexpress HER2 protein, and HER2-positivity is associated with a worse prognosis. Although HER2-targeted therapies have significantly improved outcomes for HER2-positive BC patients, resistance to trastuzumab-based therapy remains a clinical problem. In order to better understand resistance to HER2-targeted therapies in HER2-positive BC, it is necessary to examine HER family signalling as a whole. An extensive literature search was carried out to critically assess the current knowledge of HER family signalling in HER2-positive BC and response to HER2-targeted therapy. Known mechanisms of trastuzumab resistance include reduced receptor-antibody binding (MUC4, p95HER2), increased signalling through alternative HER family receptor tyrosine kinases (RTK), altered intracellular signalling involving loss of PTEN, reduced p27kip1, or increased PI3K/AKT activity and altered signalling via non-HER family RTKs such as IGF1R. Emerging strategies to circumvent resistance to HER2-targeted therapies in HER2-positive BC include co-targeting HER2/PI3K, pan-HER family inhibition, and novel therapies such as T-DM1. There is evidence that immunity plays a key role in the efficacy of HER-targeted therapy, and efforts are being made to exploit the immune system in order to improve the efficacy of current anti-HER therapies. With our rapidly expanding understanding of HER2 signalling mechanisms along with the repertoire of HER family and other targeted therapies, it is likely that the near future holds further dramatic improvements to the prognosis of women with HER2-positive BC

Survival of Patients with Resected Microsatellite Instability-High, Mismatch Repair Deficient, and Lynch Syndrome-Associated Pancreatic Ductal Adenocarcinomas

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease due to its aggressiveness, late-stage diagnosis, and limited treatment options. Microsatellite instability-high (MSI-H) cancers are susceptible to immune checkpoint inhibitors. Survival outcomes for patients with MSI-H PDAC are unknown as the disease is rare. Methods: This study included patients with PDACs surgically resected from 1990 to 2023, and those with germline or sporadic pathogenic variants in DNA mismatch repair genes were identified. The study matched MSI-H, mismatch repair-deficient (MMRd), and Lynch syndrome (LS)-associated PDAC cases (on age, gender, and year of surgery) with microsatellite-stable (MSS), mismatch repair-proficient, or non-LS-associated PDAC cases in a 1:2 ratio. A generalized estimating equation Cox model with a robust sandwich estimator was used to compare overall survival (OS) in the matched cohorts. Results: Of 936 cases, 18 were included. Eight cases were MSI-H/MMRd, two were MSI/IHC-indeterminate, seven were MSS, and one was not tested for MSI. Nine patients had LS (MLH1 [n = 1], MSH2 [n = 4], MSH6 [n = 1], PMS2 [n = 3]), and nine patients had sporadic pathogenic variants in DNA MMR genes (MLH1 [n = 4], MSH6 [n = 5]). After matching to 36 control patients, the MSI-H/MMRd/LS PDACs had a significantly better OS (hazard ratio [HR], 0.36 [95% confidence interval [CI], 0.18–0.73; p = 0.005]; 5-year OS: MSI-H 77% [95% CI 58–100%] vs. MSS 27% [95% CI 15–51%]). Conclusion: Before routine use of immune checkpoint inhibitors, the patients with MSI-H, MMRd, and LS-associated PDACs displayed significantly better survival than the patients with MSS, MMR-proficient, non-LS-associated PDACs. It is expected that survival for this cohort will further improve with increased availability of immunotherapy.</p

Gemcitabine with Cisplatin Versus Hepatic Arterial Infusion Pump Chemotherapy for Liver-Confined Unresectable Intrahepatic Cholangiocarcinoma

Background: A post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA. Methods: We retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center. Results: In total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p &lt; 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0–13.6%) in the gem-cis group versus 34.3% (95% CI 28.1–41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19–0.39). Conclusions: This study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.</p

Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer

We conducted a phase I pharmacokinetic dose escalation study of a recombinant humanized anti-p185HER2 monoclonal antibody (MKC-454) in 18 patients with metastatic breast cancer refractory to chemotherapy. Three or six patients at each dose level received 1, 2, 4 and 8 mg kg–1 of MKC-454 as 90-min intravenous infusions. The first dose was followed in 3 weeks by nine weekly doses. Target trough serum concentration has been set at 10 μg ml–1 based on in vitro observations. The mean value of minimum trough serum concentrations at each dose level were 3.58 ± 0.63, 6.53 ± 5.26, 40.2 ± 7.12 and 87.9 ± 23.5 μg ml–1 respectively. At 2 mg kg–1, although minimum trough serum concentrations were lower than the target trough concentration with a wide range of variation, trough concentrations increased and exceeded the target concentration, as administrations were repeated weekly. Finally 2 mg kg–1 was considered to be sufficient to achieve the target trough concentration by the weekly dosing regimen. One patient receiving 1 mg kg–1 had grade 3 fever, one at the 1 mg kg–1 level had severe fatigue defined as grade 3, and one at 8 mg kg–1 had severe bone pain of grade 3. No antibodies against MKC-454 were detected in any patients. Objective tumour responses were observed in two patients; one receiving 4 mg kg–1 had a partial response in lung metastases and the other receiving 8 mg kg–1 had a complete response in soft tissue metastases. These results indicate that MKC-454 is well tolerated and effective in patients with refractory metastatic breast cancers overexpressing the HER2 proto-oncogene. Further evaluation of this agent with 2–4 mg kg–1 weekly intravenous infusion is warranted. © 1999 Cancer Research Campaig

Reconstructing cancer genomes from paired-end sequencing data

<p>Abstract</p> <p>Background</p> <p>A cancer genome is derived from the germline genome through a series of somatic mutations. Somatic structural variants - including duplications, deletions, inversions, translocations, and other rearrangements - result in a cancer genome that is a scrambling of intervals, or "blocks" of the germline genome sequence. We present an efficient algorithm for reconstructing the block organization of a cancer genome from paired-end DNA sequencing data.</p> <p>Results</p> <p>By aligning paired reads from a cancer genome - and a matched germline genome, if available - to the human reference genome, we derive: (i) a partition of the reference genome into intervals; (ii) adjacencies between these intervals in the cancer genome; (iii) an estimated copy number for each interval. We formulate the Copy Number and Adjacency Genome Reconstruction Problem of determining the cancer genome as a sequence of the derived intervals that is consistent with the measured adjacencies and copy numbers. We design an efficient algorithm, called Paired-end Reconstruction of Genome Organization (PREGO), to solve this problem by reducing it to an optimization problem on an interval-adjacency graph constructed from the data. The solution to the optimization problem results in an Eulerian graph, containing an alternating Eulerian tour that corresponds to a cancer genome that is consistent with the sequencing data. We apply our algorithm to five ovarian cancer genomes that were sequenced as part of The Cancer Genome Atlas. We identify numerous rearrangements, or structural variants, in these genomes, analyze reciprocal vs. non-reciprocal rearrangements, and identify rearrangements consistent with known mechanisms of duplication such as tandem duplications and breakage/fusion/bridge (B/F/B) cycles.</p> <p>Conclusions</p> <p>We demonstrate that PREGO efficiently identifies complex and biologically relevant rearrangements in cancer genome sequencing data. An implementation of the PREGO algorithm is available at <url>http://compbio.cs.brown.edu/software/</url>.</p

Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells

Grb7 has potential importance in the progression of cancer. We have previously identified a novel peptide that binds to the SH2 domain of Grb7 and inhibits its association with several different receptor tyrosine kinases. We have synthesised the Grb7 peptide, G7-18NATE, with two different cell penetrating peptides, Penetratin and Tat. In this study, we have shown that both Penetratin- and Tat-conjugated G7-18NATE peptides are able to inhibit the proliferation of SK-BR-3, ZR-75-30, MDA-MB-361 and MDA-MB-231 breast cancer cells. There was no significant effects on breast cancer MCF-7cells, non-malignant MCF 10A or 3T3 cells. In addition, there was no significant inhibition of proliferation by Penetratin or Tat alone or by their conjugates with arbitrary peptide sequence in any of the cell lines tested. We determined the EC50 of G7-18NATE-P peptide for SK-BR-3 cell proliferation to be 7.663 × 10−6 M. Co-treatment of G7-18NATE-P peptide plus Doxorubicin in SK-BR-3 breast cancer cells resulted in an additional inhibition of proliferation, resulting in 56 and 84% decreases in the Doxorubicin EC50 value in the presence of 5 × 10−6 and 1.0 × 10−5 M G7-18NATE-P peptide, respectively. Importantly, the co-treatment with Doxorubicin and the delivery peptide did not change the Doxorubicin EC50. Since Grb7 associates with ErbB2, we assessed whether the peptide inhibitor would have a combined effect with a molecule that targets ErbB2, Herceptin. Co-treatment of Herceptin plus 1.0 × 10−5 M G7-18NATE-P peptide in SK-BR-3 cells resulted in a 46% decrease in the Herceptin EC50 value and no decrease following the co-treatment with Herceptin and penetratin alone. This Grb7 peptide has potential to be developed as a therapeutic agent alone, in combination with traditional chemotherapy, or in combination with other targeting molecules