Multiple Identity Tracking and Motion Extrapolation

Multiple Identity Tracking (MIT) is a paradigm in which individuals track the location and identity of moving objects in the environment. The first goal of the present study was to determine if individuals are able to extrapolate the position of moving objects and their identities while objects are occluded. There is conflicting research on the source of a decline in tracking ability. Either the amount of time an object is occluded for, or the distance an object moved during an occlusion (i.e., displaced) could equate to a decrease in performance. The present study aimed to evaluate which variable (occlusion time or object displacement) is more detrimental to performance. The second goal of the present study aimed to address whether individuals are able to complete a secondary task while tracking objects. The secondary task was timed with the goal of interfering with the maintenance rehearsal of the moving objects. By doing so, the present study evaluated tracking ability through an “occlusion” that involves performing a task, as many realistic occlusions occur. Twenty-five participants tracked five moving objects with unique identities over 100 trials. Response time and number of objects checked were recorded. The results indicated that participants could keep track of the objects through an occlusion with 59% accuracy. There was a difference in response time performance between slow moving and fast moving objects when they were occluded for 2 seconds, but not 4 seconds. The results suggest that tracking multiple moving objects and their identities while performing to a secondary task during an occlusion is possible, without detriment to performance in a secondary task for most individuals. Additionally, we observed a task switching cost, with participants taking longer to find the first object compared to subsequent objects

Multiple Identity Tracking and Motion Extrapolation

Multiple Identity Tracking (MIT) is a research paradigm in which individuals track the location and individual identity information of several moving objects in the environment. The present study is an examination of how individuals are able to extrapolate the future movement of moving objects while they are masked. There has been conflicting research on the source of a decline in tracking ability; either the amount of time an object is occluded for, or the distance an object moved during an occlusion. Additionally, previous research has not included the use of a secondary visual search task in a mask. Our design was modeled after a task of a pilot, who has to divide his or her attention between flight information on a head-up display (HUD) and traffic information on a horizontal situation display (HSD), while maintaining good situation awareness on both sources of information

The Grizzly, November 15, 2007

Kemper Scholarship Offers Unique Experience for Freshmen • Yale Professor Discusses Acclaimed Novel at Ursinus • UC Alumni Share Volunteer Experiences in Peace Corps • Ursinus Collects 754 Pounds of Canned Goods for Philabundance • Premium Outlet Mall Now Open • Am I Pregnant? • Spotlight: UC Wellness Fair • Kushner Would be Proud • For Music Lovers • Tortugas: In the Mood for Mexican Food? • Opinions: All-Male Housing: Damage Control; Concert Review: Tiger Army, The Static Age, and Street Dogs; Is Today\u27s Generation of Crusaders Too Online? • UC Swim Team Dives Into Season • Sororities Battle to Raise Money • Field Hockey Season Comes to an Endhttps://digitalcommons.ursinus.edu/grizzlynews/1750/thumbnail.jp

Tonic TCR Signaling Inversely Regulates the Basal Metabolism of CD4

The contribution of self-peptide-MHC signaling in CD

Investigating the Diabetic Brain: The Effects of Pioglitazone and Insulin on the Cellular Processes and Pathology of Alzheimer's Disease

Alzheimer’s disease (AD) is the sixth leading cause of death in the US. Some researchers refer to AD as “Type III Diabetes” because of reported glucose metabolism dysfunction. Preclinical studies suggest increasing insulin decreases AD pathology, although the mechanism remains unclear. To sensitize insulin signaling, this study activated Peroxisome Proliferator-Activated Receptor Gamma using intranasal co-administration of pioglitazone (PGZ) and insulin. This method targeted the site of action to reduce peripheral effects and to maximize impact in transgenic mice expressing AD pathology. Data from GC-MS fluxomics analysis suggested that PGZ+Insulin increased glucose metabolism in the brain. Immunohistochemistry with relevant antibodies was used to identify AD pathological markers in the subiculum, indicating that PGZ+Insulin decreased pathology compared to Insulin and Saline. This suggests that increasing glucose uptake in the brain alleviated AD pathology, further clarifying the role of insulin signaling in AD pathology.Gemston

Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a poor-prognosis childhood leukemia usually caused by RAS-pathway mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population. Single-cell HSPC index-sorting and clonogenic assays show that (1) all somatic mutations can be backtracked to the phenotypic HSC compartment, with RAS-pathway mutations as a "first hit,"(2) mutations are acquired with both linear and branching patterns of clonal evolution, and (3) mutant HSPCs are present after allogeneic HSC transplant before molecular/clinical evidence of relapse. Stem cell assays reveal interpatient heterogeneity of JMML LSCs, which are present in, but not confined to, the phenotypic HSC compartment. RNA sequencing of JMML LSC reveals upregulation of stem cell and fetal genes (HLF, MEIS1, CNN3, VNN2, and HMGA2) and candidate therapeutic targets/biomarkers (MTOR, SLC2A1, and CD96), paving the way for LSC-directed disease monitoring and therapy in this disease

Topo IV is the topoisomerase that knots and unknots sister duplexes during DNA replication

DNA topology plays a crucial role in all living cells. In prokaryotes, negative supercoiling is required to initiate replication and either negative or positive supercoiling assists decatenation. The role of DNA knots, however, remains a mystery. Knots are very harmful for cells if not removed efficiently, but DNA molecules become knotted in vivo. If knots are deleterious, why then does DNA become knotted? Here, we used classical genetics, high-resolution 2D agarose gel electrophoresis and atomic force microscopy to show that topoisomerase IV (Topo IV), one of the two type-II DNA topoisomerases in bacteria, is responsible for the knotting and unknotting of sister duplexes during DNA replication. We propose that when progression of the replication forks is impaired, sister duplexes become loosely intertwined. Under these conditions, Topo IV inadvertently makes the strand passages that lead to the formation of knots and removes them later on to allow their correct segregation

EZH2 modifies sunitinib resistance in renal cell carcinoma by kinome reprogramming

Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represent a major hurdle in improving the management of clear cell renal cell carcinoma (ccRCC). Recent reports suggest that drug resistance is driven by tumor adaptation via epigenetic mechanisms that activate alternative survival pathways. The histone methyl transferase EZH2 is frequently altered in many cancers including ccRCC. To evaluate its role in ccRCC resistance to RTKi, we established and characterized a spontaneously metastatic, patient-derived xenograft (PDX) model that is intrinsically resistant to the RTKI sunitinib but not to the VEGF therapeutic antibody bevacizumab. Sunitinib maintained its anti-angiogenic and anti-metastatic activity but lost its direct anti-tumor effects due to kinome reprogramming, which resulted in suppression of pro- apoptotic and cell cycle regulatory target genes. Modulating EZH2 expression or activity suppressed phosphorylation of certain RTK, restoring the anti-tumor effects of sunitnib in models of acquired or intrinsically resistant ccRCC. Overall, our results highlight EZH2 as a rational target for therapeutic intervention in sunitinib-resistant ccRCC as well as a predictive marker for RTKi response in this disease.This research was funded by Roswell Park Cancer Institute’s Cancer Center Support Grant from National Cancer Institute, NIH P30CA016056 (RP) and a generous donation by Richard and Deidre Turner (RP). This investigation was conducted in-part in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR020128-01 from the National Center for Research Resources, National Institutes of Health

Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma

Abstract Background The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. Methods We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR) and confocal immunofluorescence. Results Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. Conclusions Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets

Biogeochemical iron budgets of the Southern Ocean south of Australia : decoupling of iron and nutrient cycles in the subantarctic zone by the summertime supply

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 23 (2009): GB4034, doi:10.1029/2009GB003500.Climate change is projected to significantly alter the delivery (stratification, boundary currents, aridification of landmasses, glacial melt) of iron to the Southern Ocean. We report the most comprehensive suite of biogeochemical iron budgets to date for three contrasting sites in subantarctic and polar frontal waters south of Australia. Distinct regional environments were responsible for differences in the mode and strength of iron supply mechanisms, with higher iron stocks and fluxes observed in surface northern subantarctic waters, where atmospheric iron fluxes were greater. Subsurface waters southeast of Tasmania were also enriched with particulate iron, manganese and aluminum, indicative of a strong advective source from shelf sediments. Subantarctic phytoplankton blooms are thus driven by both seasonal iron supply from southward advection of subtropical waters and by wind-blown dust deposition, resulting in a strong decoupling of iron and nutrient cycles. We discuss the broader global significance our iron budgets for other ocean regions sensitive to climate-driven changes in iron supply.T.W. was supported by a BDI grant from CNRS and Région PACA, by CNRS PICS project 3604, and by the “Soutien à la mer” CSOA CNRS-INSU. P.W.B. was supported by the New Zealand FRST Coasts and Oceans OBI. This research was supported by the Australian Government Cooperative Research Centres Programme through the Antarctic Climate and Ecosystems CRC (ACE CRC) and Australian Antarctic Science project 2720