Tesis sobre el tema "Promodès"

Transforming Growth Factor Beta Induced Gene Human Clone 3, BIGH3, is an extra cellular matrix protein expressed by different cell types. BIGH3 promotes cell adhesion and has been recognized as a tumor suppressor protein in many studies, a function consistent with the finding that the expression of BIGH3 is reduced in various tumors and transformed cells when compared to healthy counterparts.

In the present study, we found that BIGH3 induces MG63 multi tumor spheroid (MTS) cells apoptosis and antagonized the development of tumor cells into large aggregate, supporting BIGH3 tumor suppressor role. MG63 spheroids were cultured in recombinant BIGH3 and vascular smooth muscle cells (VSMCs) conditioned medium . We have shown BIGH3 to be abundantly expressed by VSMCs. In addition, stimulation of BIGH3 gene by TGF-β1 in MG63 cells resulted in overexpression of BIGH3 and subsequent increase in apoptosis by almost 3 fold. TUNEL assay was performed to detect apoptotic cells. Smaller and scattered tumor spheroids were observed in TGF-β1 treated cells. Importantly, in-house developed anti- BIGH3 antibody reduced apoptosis percentage by almost one-half and antagonized the development of osteosarcoma cells into large aggregate spheroids. Within the formed spheroids, BIGH3 was immunologically detected in in the stroma and at cell bodies, suggesting a possible binding of BIGH3 to the cell surface. Collectively, these data suggest that BIGH3 plays a suppressive role in development of osteosarcoma tumor spheroids.

MG63 were cultured in agar-coated wells, where they developed into 3D aggregates. Unlike classical monolayer-based models (2D), multicellular tumor spheroid (MTS) cell culture system mimics the in vivo 3D structure of a solid tumor.

Disengagement has been identified as a significant and persistent problem across broad swaths of modern life. Lack of participation in political and civic affairs poses an existential threat to public institutions and the fabric of our democracy (e.g., Delli Carpini, 2000; Prior, 2007). Failures to heed recommended guidelines and treatment plans cause epidemic-levels of unnecessary illness and premature death (e.g., Cramer, Benedict, Muszbek, Keskinaslan, & Khan, 2008; Ramanadhan & Viswanath, 2006). Worker apathy, employee turnover, and active disengagement cost organizations and their stakeholders billions of dollars annually (e.g., Gallup, 2013; Rampersad, 2006).

Despite exposure to countless admonitions to get involved, take better care of themselves, and work harder or smarter, many people simply do not do what their leaders, doctors, bosses, and other pro-social advocates tell them is good for them. Perceptions of problematic disengagement have led to thousands of public communication campaigns (Rice & Atkin, 2012; Snyder et al., 2004) focused on addressing these problems. Many such campaigns, however, have been described as being most effective on those who least need to change, and least effective on those whose behavior is deemed most problematic. The current study grew out of suspicions that efforts to address issues of problematic disengagement may actually serve to sustain or even exacerbate disparities in engagement. To test this possibility, the study examined the effects of two different theory-based pro-social advocacy message strategies on subjects at different levels of pre-existing positive engagement in pro-social activities within three different but common contexts of life: political and civic affairs, personal health, and the workplace. One of the strategies employed a “typical” directive message based on the theory of planned behavior (TPB; Ajzen, 1991, 2012). As a contrasting alternative, the other strategy employed an autonomy-supportive message based on self-determination theory (SDT; Ryan & Deci, 2000, 2008). A non-persuasive control message was also tested to provide a comparison. The findings suggested that, compared to the control message, both persuasive message strategies led to greater disparities in post-test engagement between groups with the lowest levels of pre-existing pro-social engagement and groups with higher levels.

A foundational hypothesis, acknowledging the powerful influence of past behavior on future behavior, predicted that (H1) subjects’ pre-existing levels of pro-social engagement (i.e., pre-test engagement) would have a significant effect on their expectations of engagement in performing pro-social behaviors in the future (i.e., post-test engagement). A subsequent series of hypotheses predicted that, in addition to the main effect predicted in H1, pre-test engagement would moderate the effect of the TPB-based advocacy message on post-test engagement (H2). The results of this interaction effect would be that (H2a) among subjects with the lowest levels of pre-test engagement, the TPB-based directive message strategy would be no more effective in promoting post-test engagement than the control message, but that (H2b) among subjects at higher pre-test engagement levels, the TPB-based message would lead to greater post-test engagement than the control message. The result of these two outcomes (H2c) would be greater disparities in post-test engagement between groups lowest in pre-test engagement and groups with higher levels of pre-test engagement. These hypotheses were supported.

A research question explored whether the SDT-based autonomy-support message, as an alternative strategy, would be more effective (again, compared to the control message) in promoting greater post-test engagement among groups at all levels of pre-test engagement and thereby avoid promoting greater disparities. However, analyses showed that the SDT-based message also produced greater disparities in post-test engagement between the groups that were lowest in pre-test engagement and the groups at higher pre-test engagement levels.

A final hypothesis (H3), that the interaction effects between message type and level of pre-test engagement would be consistent across all three domains examined in the study, was also supported. This provided support for the notion that the tendency of pro-social advocacy messages to promote greater disparities between groups that could be termed the “haves” and “have nots” of society might be generalizable to more situations than those examined in the current study, and therefore worthy of further research. The implications of these findings for future research and practical application are explored in the discussion section that concludes this dissertation.

Hacktivist activity is becoming increasingly prominent within the cyber domain and society. The boundaries between cyber terrorism and hacktivism are becoming more unclear. Hackers are becoming more skilled and involved in socio-political matters, not only in the U.S. but also internationally. Terrorist groups like the Islamic State of Iraq and Syria (ISIS) have found a venue to voice their ideals and recruit via social media. Furthermore, terrorist groups have partnerships with hacktivist groups such as Cyber Caliphates. This practice has pointed particular inclinations that characterize different hacker groups with different events. For this reason, computer security has become a matter of national security in the U.S. and research regarding political and socio-economic trends as stimuli for the increment on hacktivist activity must be conducted. This research explored the issue of profiling hacktivist groups, departing from the analysis of the hacker’s motivation as a product of a political and socio-economic environment. As comparative angles of analysis, the literature exposed empirical and factual information that integrated U.S. and international hacktivist events. The final research analysis proposed that U.S. political and socio-economic trends promoted hacktivist activity. Moreover, the research exposed that the existent relationship between extrinsic and intrinsic stimuli with political and socio-economical stressors (i.e., misrepresentation, restriction of freedoms, frustration and aggression) promotes hackers to act as hacktivists. Keywords: Psychological profiling; Professor Riddell, Hackers; Hacktivist; Hacktivism; Political Hacktivism; Socio-economic Hacktivism; Extrinsic stimuli; Intrinsic stimuli; Cyber Diplomacy; Cyber Constitution; Cybercrime Awareness Normalization Unit.

Activin B, a TGFβ ligand, is associated with liver inflammatory response. We aimed to investigate whether it modulates liver fibrogenesis. Liver and serum activin B, along with its analog activin A, were analyzed in patients with liver fibrosis from different etiologies and in mouse acute liver injury and liver fibrosis models. Activin B, activin A, or both was immunologically neutralized in progressive or established carbon tetrachloride-induced mouse liver fibrosis. The direct effects of activin B and A on hepatocytes, macrophages, and hepatic stellate cells (HSCs) were evaluated in vitro. In human patients, increased activin B is associated with liver fibrosis irrespective of the etiologies. In mice, activin B exhibited persistent elevation in liver and circulation following the onset of liver injury, whereas activin A displayed transient increases. Neutralizing activin B largely prevented and remarkably regressed liver fibrosis, which was augmented by co-neutralizing activin A in mice. Mechanistically, activin B promoted hepatocyte injury, activated macrophages to release cytokines, and induced a pro-fibrotic expression profile and septa formation in HSCs, which were magnified by activin A. Furthermore, activin B and A interdependently activated the CXCL1/iNOS pathway in macrophages and additively upregulated CTGF transcript in HSCs in vitro. Consistently, the expression of these genes was prohibited by neutralizing either one of these two ligands in injured livers. Activin B potently drives the initiation and progression of liver fibrogenesis. It additively or interdependently cooperates with activin A, directly acts on multiple liver cell populations, and induces liver fibrogenesis. Antagonizing activin B or both activins B and A prevents and regresses liver fibrosis in mouse CCl₄ model, inspiring the development of a novel therapy of chronic liver diseases.