How do I Know what you Know? A Novel Theoretical Account of Epistemic Inference

Of the capacities that make us uniquely human—pedagogy, social learning, coop- eration, communication, moral evaluation—all hinge, at least in part, on an under- standing of what others know or believe. Critically, we cannot see mental states: we have access only to the observable behaviors they cause. So, to navigate the social world, we must often infer what others think from observing what they do. While prior work has investigated how children and adults infer preferences, goals, and desires from behavior, little research has investigated how we infer epistemic states (knowledge and beliefs). In this thesis, I expand upon existing accounts of mental state reasoning to formalize a novel theoretical account of epistemic inference. I test whether this account captures adults’ knowledge inferences, and use it to systemati- cally investigate the development of our capacities

Stem Cells and Metastatic Cancer: Fatal Attraction?

Fodde discusses a new study in PLoS ONE, by Aboody and colleagues, who report on the successful eradication of whole-body disseminated metastases in a mouse model of neuroblastoma

What drives executive stock option backdating?

We study motives for executive stock option backdating, the practice of changing the grant dates of current options to dates in the past using hindsight. We find that smaller, younger, and less profitable firms tend to be heavier involved in backdating. These results are consistent with the retention hypothesis. In line with the incentive hypothesis, we find that backdating occurs more for options that are out-of-the-money. We derive some evidence for the agency hypothesis, in the sense that backdating companies have a larger percentage of inside directors. However, contrary to this hypothesis, we conclude that backdating firms have better protection for minority shareholders compared to firms that do not backdate

Detection of Cryptosporidium parvum by modified acid-fast stain among cancer patients in Thi-Qar province

Cryptosporidium parvum is a widespread opportunistic parasite belonging to the family Apicomplexa that completes its life cycle in a single host and is found frequently in immunocompromised persons, especially in patients with cancer. This research's objectives were to determine the prevalence of Cryptosporidium parvum infection among cancer patients in the Thi-Qar Province of Iraq, using modified Ziehl-Neelsen (MZN) stain. This study included 300 stool samples, 200 of which were for patients with cancer and 100 were for healthy people (the control group). Based on the modified acid-fast stain, the results showed the rate of infection with Cryptosporidium parvum among cancer patients was 54.0% (108/200) compared to 30.0% (30/100) in the control group, and there were statistically significant differences between them .And the percentage of infection among cancer patients in males was higher than in females, but there were no significant differences between them, as the percentage was 57.14% and 52.03%, respectively. As for the age groups Cryptosporidium parvum it affects all age groups in different proportions. The study showed that the highest infection rate among the age groups reached ?60 years at a rate of 64.44%, and the lowest infection rate among the age group ?20 years at a rate of 35.71%. As for the number doses of chemotherapy the results showed that the infection rate  was higher in patients who received half and more than half of the doses of chemotherapy, where the percentage of those who received 16-20 doses (64.0%) 

SLC7A11 Overexpression in Glioblastoma Is Associated with Increased Cancer Stem Cell-Like Properties

System x_c^− is a sodium-independent electroneutral transporter, comprising a catalytic subunit xCT (SLC7A11), which is involved in importing cystine. Certain cancers such as gliomas upregulate the expression of system x_c^−, which confers a survival advantage against the detrimental effects of reactive oxygen species (ROS) by increasing generation of the antioxidant glutathione. However, ROS have also been shown to function as targeted, intracellular second messengers in an array of physiological processes such as proliferation. Several studies have implicated ROS in important cancer features such as migration, invasion, and contribution to a cancer stem cell (CSC)-like phenotype. The role of system x_c^− in regulating these ROS-sensitive processes in glioblastoma multiforme (GBM), the most aggressive malignant primary brain tumor in adults, remains unknown. Stable SLC7A11 knockdown and overexpressing U251 glioma cells were generated and characterized to understand the role of redox and system x_c^− in glioma progression. SLC7A11 knockdown resulted in higher endogenous ROS levels and enhanced invasive properties. On the contrary, overexpression of SLC7A11 resulted in decreased endogenous ROS levels as well as decreased migration and invasion. However, SLC7A11-overexpressing cells displayed actin cytoskeleton changes reminiscent of epithelial-like cells and exhibited an increased CSC-like phenotype. The enhanced CSC-like phenotype may contribute to increased chemoresistance and suggests that overexpression of SLC7A11 in the context of GBM may contribute to tumor progression. These findings have important implications for cancer management where targeting system x_C^− in combination with other chemotherapeutics can reduce cancer resistance and recurrence and improve GBM patient survival

Mesenchymal Stem Cells Modified with a Single-Chain Antibody against EGFRvIII Successfully Inhibit the Growth of Human Xenograft Malignant Glioma

Glioblastoma multiforme is the most lethal brain tumor with limited therapeutic options. Antigens expressed on the surface of malignant cells are potential targets for antibody-mediated gene/drug delivery.In this study, we investigated the ability of genetically modified human mesenchymal stem cells (hMSCs) expressing a single-chain antibody (scFv) on their surface against a tumor specific antigen, EGFRvIII, to enhance the therapy of EGFRvIII expressing glioma cells in vivo. The growth of U87-EGFRvIII was specifically delayed in co-culture with hMSC-scFvEGFRvIII. A significant down-regulation was observed in the expression of pAkt in EGFRvIII expressing glioma cells upon culture with hMSC-scFvEGFRvIII vs. controls as well as in EGFRvIII expressing glioma cells from brain tumors co-injected with hMSC-scFvEGFRvIII in vivo. hMSC expressing scFvEGFRvIII also demonstrated several fold enhanced retention in EGFRvIII expressing flank and intracranial glioma xenografts vs. control hMSCs. The growth of U87-EGFRvIII flank xenografts was inhibited by 50% in the presence of hMSC-scFvEGFRvIII (p<0.05). Moreover, animals co-injected with U87-EGFRvIII and hMSC-scFvEGFRvIII intracranially showed significantly improved survival compared to animals injected with U87-EGFRvIII glioma cells alone or with control hMSCs. This survival was further improved when the same animals received an additional dosage of hMSC-scFvEGFRvIII two weeks after initial tumor implantation. Of note, EGFRvIII expressing brain tumors co-injected with hMSCs had a lower density of CD31 expressing blood vessels in comparison with control tumors, suggesting a possible role in tumor angiogenesis.The results presented in this study illustrate that genetically modified MSCs may function as a novel therapeutic vehicle for malignant brain tumors

Increased Expression of System x_c^- in Glioblastoma Confers an Altered Metabolic State and Temozolomide Resistance

Glioblastoma multiforme is the most aggressive malignant primary brain tumor in adults. Several studies have shown that glioma cells upregulate the expression of xCT (SLC7A11), the catalytic subunit of system x_c^-, a transporter involved in cysteine import, that modulates glutathione production and glioma growth. However, the role of system x_c^- in regulating the sensitivity of glioma cells to chemotherapy is currently debated. Inhibiting system x_c^- with sulfasalazine decreased glioma growth and survival via redox modulation, and use of the chemotherapeutic agent temozolomide together with sulfasalazine had a synergistic effect on cell killing. To better understand the functional consequences of system x_c^- in glioma, stable SLC7A11-knockdown and -overexpressing U251 glioma cells were generated. Modulation of SLC7A11 did not alter cellar proliferation but overexpression did increase anchorage-independent cell growth. Knockdown of SLC7A11 increased basal reactive oxygen species (ROS) and decreased glutathione generation resulting in increased cell death under oxidative and genotoxic stress. Overexpression of SLC7A11 resulted in increased resistance to oxidative stress and decreased chemosensitivity to temozolomide. In addition, SLC7A11 overexpression was associated with altered cellular metabolism including increased mitochondrial biogenesis, oxidative phosphorylation, and ATP generation. These results suggest that expression of SLC7A11 in the context of glioma contributes to tumorigenesis, tumor progression, and resistance to standard chemotherapy

Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Lung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer.</p> <p>Methods</p> <p>A mouse syngeneic lung carcinoma model was used to test the basic ability of UCMSCs to control the growth of lung cancer. Lung tumors were experimentally induced by tail vein administration of Lewis lung carcinoma (LLC) cells derived from the lung of C57BL/6 mouse. Rat UCMSCs were then administered intratracheally five days later or intravenously on days 5 and 7. The tumor burdens were determined by measuring lung weight three weeks after the treatment.</p> <p>Results</p> <p>Co-culture of rat UCMSCs with LLC significantly attenuated the proliferation of LLC cells as monitored by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), a tetrazole cell proliferation assay, thymidine uptake, and direct cell counts. <it>In vitro </it>colony assays with rat UCMSCs as feeder layers markedly reduced LLC colony size and number. Co-culture of rat UCMSCs with LLCs causes G0/G1 arrest of cancer cells. This is evident in the decrease of cyclin A and CDK2 expression. The <it>in vivo </it>studies showed that rat UCMSC treatment significantly decreased tumor weight and the total tumor mass. Histological study revealed that intratracheally or systemically administered rat UCMSCs homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects.</p> <p>Conclusions</p> <p>These results indicate that rat UCMSCs alone remarkably attenuate the growth of lung carcinoma cells <it>in vitro </it>and in a mouse syngeneic lung carcinoma graft model and could be used for targeted cytotherapy for lung cancer.</p

Prevalence of Toxoplasma gondii among immunocompromised patients (heamodialysis and cancer) in the province of Thi-Qar-Iraq

The current study was conducted in Thi-Qar province to investigate  of Toxoplasma gondii  prevalence among  renal dialysis and cancer patients by using anti-Toxoplasmosis IgG and IgM by ELISA also the study determined of some factors that may  affected the  prevalence of infection, such as age, sex, marital status, place of residence and a number of chemical dosing that exposed to it  cancer patient or the number of times the dialysis for renal dialysis patients.                                              The results of the current study showed that the prevalence of toxoplasmosis in Thi-Qar province in both renal dialysis and cancer patients and control group were 28% and 36% and 24% respectively. recorded results of Enzyme Linked Immunosorbent Assay ELISA test results for a positive antibody IgG in both renal dialysis and cancer patients and control group 25% , 30% , 22% respectively. As for the IgM antibody study did not record any positive result in both categories of the study (dialysis and cancer) only  control group was 2%. The result of IgG & IgM together in renal dialysis and cancer and control group 3%, 6%, 0% respectively. The study found that the increase in the number of times the dialysis increased incidence of infection prevalence it was 25.53% for patients who conducted the dialysis treatment more than six times and 16.66% for patients who have less than six times.For factor chemical dosing show high infection rates in patients who have been exposed to more than one dose of a chemical 37.63% As for those who were not  exposed to any chemical dose was ratios have 14.29%

Prevalence of Toxoplasma gondii among immunocompromised patients (heamodialysis and cancer) in the province of Thi-Qar-Iraq

The current study was conducted in Thi-Qar province to investigate  of Toxoplasma gondii  prevalence among  renal dialysis and cancer patients by using anti-Toxoplasmosis IgG and IgM by ELISA also the study determined of some factors that may  affected the  prevalence of infection, such as age, sex, marital status, place of residence and a number of chemical dosing that exposed to it  cancer patient or the number of times the dialysis for renal dialysis patients.                                              The results of the current study showed that the prevalence of toxoplasmosis in Thi-Qar province in both renal dialysis and cancer patients and control group were 28% and 36% and 24% respectively. recorded results of Enzyme Linked Immunosorbent Assay ELISA test results for a positive antibody IgG in both renal dialysis and cancer patients and control group 25% , 30% , 22% respectively. As for the IgM antibody study did not record any positive result in both categories of the study (dialysis and cancer) only  control group was 2%. The result of IgG & IgM together in renal dialysis and cancer and control group 3%, 6%, 0% respectively. The study found that the increase in the number of times the dialysis increased incidence of infection prevalence it was 25.53% for patients who conducted the dialysis treatment more than six times and 16.66% for patients who have less than six times.For factor chemical dosing show high infection rates in patients who have been exposed to more than one dose of a chemical 37.63% As for those who were not  exposed to any chemical dose was ratios have 14.29%