1,167 research outputs found
Using Augmented Reality in Software Engineering Education? First insights to a comparative study of 2D and AR UML modeling
Although there has been much speculation about
the potential of Augmented Reality (AR) in teaching for
learning material, there is a significant lack of empirical
proof about its effectiveness and implementation in
higher education. We describe a software to integrate
AR using the Microsoft Hololens into UML (Unified
Modeling Language) teaching. Its user interface is
laid out to overcome problems of existing software.
We discuss the design of the tool and report a first
evaluation study. The study is based upon effectiveness
as a metric for students performance and components
of motivation. The study was designed as control
group experiment with two groups. The experimental
group had to solve tasks with the help of the AR
modeling tool and the control group used a classic PC
software. We identified tendencies that participants of
the experimental group showed more motivation than
the control group. Both groups performed equally well
CTLA4 blockade increases Th17 cells in patients with metastatic melanoma
<p>Abstract</p> <p>Background</p> <p>Th17 cells are CD4+ cells that produce interleukin 17 (IL-17) and are potent inducers of tissue inflammation and autoimmunity. We studied the levels of this T cell subset in peripheral blood of patients treated with the anti-CTLA4 antibody tremelimumab since its major dose limiting toxicities are inflammatory and autoimmune in nature.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMC) were collected before and after receiving tremelimumab within two clinical trials, one with tremelimumab alone (21 patients) and another together with autologous dendritic cells (DC) pulsed with the melanoma epitope MART-1<sub>26–35 </sub>(6 patients). Cytokines were quantified directly in plasma from patients and after <it>in vitro </it>stimulation of PBMC. We also quantified IL-17 cytokine-producing cells by intracellular cytokine staining (ICS).</p> <p>Results</p> <p>There were no significant changes in 13 assayed cytokines, including IL-17, when analyzing plasma samples obtained from patients before and after administration of tremelimumab. However, when PBMC were activated <it>in vitro</it>, IL-17 cytokine in cell culture supernatant and Th17 cells, detected as IL-17-producing CD4 cells by ICS, significantly increased in post-dosing samples. There were no differences in the levels of Th17 cells between patients with or without an objective tumor response, but samples from patients with inflammatory and autoimmune toxicities during the first cycle of therapy had a significant increase in Th17 cells.</p> <p>Conclusion</p> <p>The anti-CTLA4 blocking antibody tremelimumab increases Th17 cells in peripheral blood of patients with metastatic melanoma. The relation between increases in Th17 cells and severe autoimmune toxicity after CTLA4 blockade may provide insights into the pathogenesis of anti-CTLA4-induced toxicities.</p> <p>Trial Registration</p> <p><b>Clinical trial registration numbers</b>: NCT0090896 and NCT00471887</p
Monitoring of hadrontherapy treatments by means of charged particle detection
The interaction of the incoming beam radiation with the patient body in hadrontherapy
treatments produces secondary charged and neutral particles, whose detection can be
used for monitoring purposes and to perform an on-line check of beam particle range. In
the context of ion-therapy with active scanning, charged particles are potentially attractive
since they can be easily tracked with a high efficiency, in presence of a relatively low
background contamination. In order to verify the possibility of exploiting this approach
for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both
simulations and experimental tests are being performed with ion beams impinging on
simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the
order of few millimeters on the single track has been proven to be sufficient to exploit
charged particle tracking for monitoring purposes, preserving the precision achievable
on longitudinal shape. The results obtained so far show that the measurement of charged
particles can be successfully implemented in a technology capable of monitoring both
the dose profile and the position of the Bragg peak inside the target and finally lead to
the design of a novel profile detector. Crucial aspects to be considered are the detector
positioning, to be optimized in order to maximize the available statistics, and the capability
of accounting for the multiple scattering interactions undergone by the charged
fragments along their exit path from the patient body. The experimental results collected
up to now are also valuable for the validation of Monte Carlo simulation software tools
and their implementation in Treatment Planning Software packages
Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations
<p>Abstract</p> <p>Background</p> <p>A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines.</p> <p>Materials and methods</p> <p>The combination of the BRAF inhibitor vemurafenib (formerly PLX4032) and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot.</p> <p>Results</p> <p>Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRAS<sup>Q61K </sup>mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAF<sup>V600E </sup>mutants, including highly synergistic effects in two BRAF<sup>V600E </sup>mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAF<sup>V600E </sup>mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways.</p> <p>Conclusions</p> <p>The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAF<sup>V600E </sup>mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.</p
The Grizzly, February 26, 1991
The Gulf War: How Will It Affect the Economy? • Airband Competition Enters Its Eighth Year • Sears-Roebuck Award, A Boon for Faculty • How Will the War End? • My First College Field Trip • McCabe Wins Contest • John Lionarons Performs • Dan Pasquale • Steel Magnolias • L.A Story • Peter Benchley\u27s Rummies • Flatliners • Former Monsters of Rock • City Art: Pop Art Prints • Angelos Resigns as Head Basketball Coach at Ursinus • Swimmers Place High at MAC Championships • Lady Bears Look to ECAC Play-off • Track Women Improve at Invitational • Wrestlers Place Fourth at MAC\u27s • Letter: Schafer Bashes Harley\u27s Haven • I Cannot Accept it • Most Selective - Bio/Pre-Med at Ursinus • Feeling lazy? -Could be CFS • Science Careershttps://digitalcommons.ursinus.edu/grizzlynews/1272/thumbnail.jp
The Grizzly, March 19, 1991
New U.S.G.A Officers Appointed • Pennsylvania Pro-Life Convention Held • Rare Israeli Exhibition Arrives Safely • Village Idiots Compete at Pitt • Tenure Candidates Approved for Next Year • Alcohol Recovery Group to Start • Seniors Prepare for Graduation • Just Do It -- The Nautilus Connection • Flags: The Collegeville Connection • U.S.G.A Minutes • The Knack is Bnack! • Ursinus Students in Indonesia for a Day • Julian\u27s House • Meistersingers • Talking With Betty Boop • Bowie: Something Old and Something New • City of David at Berman • Men\u27s Lacrosse Club Wins Season Opener • Tennis Teams Begin Season • Five Named to MAC Honor Roll • Softball Starts Season • Baseball World Tour \u2791 • Indoor Track Finishes Season • Letter: On Teaching Catalan • Student Apathy is Growing • Consider Women\u27s Studies Next Semesterhttps://digitalcommons.ursinus.edu/grizzlynews/1273/thumbnail.jp
Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032
Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity
The Grizzly, September 25, 1990
New Student Center Planned for Wismer • Homeland Ministries Honors Landis • Class of 1994 Elects Officers • Parents Day 1990 • The Intifada: A Palestinian View • Myrin Booksale Upcoming • Welcome Class of \u2794 • Japanese Teacher Certification: Ursinus First in State • Bridging the Gap • They are Here! • Clark Publishes Article • Phi Alpha Psi Holds Service Project • Rushing Draws to a Close • Campus Shocker!: WVOU Works • Record Review • Current Berman • Fun Forum • Men Sweep Golden Bear Classic • Wenger Returns in Win • BWC Holds Tournament • Bears Still Can\u27t Beat WM\u27s Jinx • Soccer Team Soars • Women Wait for Warner • Liberals, Stop Legislating from the Bench! • Letters: Clark Calls Japanese Coverage Poor; Hafer\u27s Mortality Statistics Disputed • Ursinus at Woods Hole • The Price of Chemistryhttps://digitalcommons.ursinus.edu/grizzlynews/1258/thumbnail.jp
Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway
The sustained clinical activity of the BRAF inhibitor vemurafenib (PLX4032/RG7204) in patients with BRAF(V600) mutant melanoma is limited primarily by the development of acquired resistance leading to tumor progression. Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway.The sensitivity to vemurafenib or the MEK inhibitor AZD6244 was tested in sensitive and resistant human melanoma cell lines exploring differences in activation-associated phosphorylation levels of major signaling molecules, leading to the testing of co-inhibition of the AKT/mTOR pathway genetically and pharmacologically. There was a high degree of cross-resistance to vemurafenib and AZD6244, except in two vemurafenib-resistant cell lines that acquired a secondary mutation in NRAS. In other cell lines, acquired resistance to both drugs was associated with persistence or increase in activity of AKT pathway. siRNA-mediated gene silencing and combination therapy with an AKT inhibitor or rapamycin partially or completely reversed the resistance.Primary and acquired resistance to vemurafenib in these in vitro models results in frequent cross resistance to MEK inhibitors, except when the resistance is the result of a secondary NRAS mutation. Resistance to BRAF or MEK inhibitors is associated with the induction or persistence of activity within the AKT pathway in the presence of these drugs. This resistance can be potentially reversed by the combination of a RAF or MEK inhibitor with an AKT or mTOR inhibitor. These combinations should be available for clinical testing in patients progressing on BRAF inhibitors
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