Showing papers by "University of South Florida published in 2001"

Understanding information systems continuance: an expectation-confirmation model

Abstract: This paper examines cognitive beliefs and affect influencing one's intention to continue using (continuance) information systems (IS). Expectation-confirmation theory is adapted from the consumer behavior literature and integrated with theoretical and empirical findings from prior IS usage research to theorize a model of IS continuance. Five research hypotheses derived from this model are empirically validated using a field survey of online banking users. The results suggest that users' continuance intention is determined by their satisfaction with IS use and perceived usefulness of continued IS use. User satisfaction, in turn, is influenced by their confirmation of expectation from prior IS use and perceived usefulness. Post-acceptance perceived usefulness is influenced by users' confirmation level. This study draws attention to the substantive differences between acceptance and continuance behaviors, theorizes and validates one of the earliest theoretical models of IS continuance, integrates confirmation and user satisfaction constructs within our current understanding of IS use, conceptualizes and creates an initial scale for measuring IS continuance, and offers an initial explanation for the acceptance-discontinuance anomaly.

High-κ gate dielectrics: Current status and materials properties considerations

Abstract: Many materials systems are currently under consideration as potential replacements for SiO2 as the gate dielectric material for sub-0.1 μm complementary metal–oxide–semiconductor (CMOS) technology. A systematic consideration of the required properties of gate dielectrics indicates that the key guidelines for selecting an alternative gate dielectric are (a) permittivity, band gap, and band alignment to silicon, (b) thermodynamic stability, (c) film morphology, (d) interface quality, (e) compatibility with the current or expected materials to be used in processing for CMOS devices, (f) process compatibility, and (g) reliability. Many dielectrics appear favorable in some of these areas, but very few materials are promising with respect to all of these guidelines. A review of current work and literature in the area of alternate gate dielectrics is given. Based on reported results and fundamental considerations, the pseudobinary materials systems offer large flexibility and show the most promise toward success...

Family-Supportive Work Environments: The Role of Organizational Perceptions

Abstract: The present study examines global employee perceptions regarding the extent their work organization is family-supportive (FSOP). Data gathered from 522 participants employed in a variety of occupations and organizations indicated that FSOP responses related significantly to the number of family-friendly benefits offered by the organization, benefit usage, and perceived family support from supervisors. FSOP responses also explained a significant amount of unique variance associated with work–family conflict, job satisfaction, organizational commitment, and turnover intentions above and beyond the variance explained by the number of family-friendly benefits available by the organization and supervisor support. Results indicated that FSOP mediates the relationship between family-friendly benefits available and the dependent variables of work–family conflict, affective commitment, and job satisfaction. FSOP also mediated the relationship between supervisor support and work–family conflict. The results underscore the important role that perceptions of the overall work environment play in determining employee reactions to family-friendly benefit policies.

Thin-Ideal Internalization: Mounting Evidence for a New Risk Factor for Body-Image Disturbance and Eating Pathology:

Abstract: Body-image disturbance and eating disorders are a significant physical and mental health problem in Western countries. We describe emerging work on one newly identified variable that appears to be a potent risk factor for the development of these problems internalization of societal standards of attractiveness. Work conducted independently in our labs over the past decade has included scale development, correlational studies, prospective risk-factor studies, randomized experiments, and randomized prevention trials. Findings collectively suggest that internalization is a causal risk factor for body-image and eating disturbances, and that it appears to operate in conjunction with other established risk factors for these outcomes, including dieting and negative affect. Future research is needed to examine the specific familial, peer, and media influences that promote internalization and to replicate and extend our prospective and experimental studies.

Intravenous Administration of Human Umbilical Cord Blood Reduces Behavioral Deficits After Stroke in Rats

Abstract: Background and Purpose— Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro. Methods— Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: group 1, MCAO alone (n=5); group 2, 3×106 HUCBC injected into tail vein at 24 hours after MCAO (n=6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (n=5); group 4, MCAO injected with PBS at 1 day after stroke (n=8); and group 5, 3×106 HUCBC injected into tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurological Severity Score [mNSS]) were performed. Immunohistoc...

Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells.

Abstract: Constitutive activation of signal transducer and activator of transcription (STAT) proteins has been detected in a wide variety of human primary tumor specimens and tumor cell lines including blood malignancies, head and neck cancer, and breast cancer. We have previously demonstrated a high frequency of Stat3 DNA-binding activity that is constitutively-induced by an unknown mechanism in human breast cancer cell lines possessing elevated EGF receptor (EGF-R) and c-Src kinase activities. Using tyrosine kinase selective inhibitors, we show here that Src and JAK family tyrosine kinases cooperate to mediate constitutive Stat3 activation in the absence of EGF stimulation in model human breast cancer cell lines. Inhibition of Src or JAKs results in dose-dependent suppression of Stat3 DNA-binding activity, which is accompanied by growth inhibition and induction of programmed cell death. In addition, transfection of a dominant-negative form of Stat3 leads to growth inhibition involving apoptosis of breast cancer cells. These results indicate that the biological effects of the Src and JAK tyrosine kinase inhibitors are at least partially mediated by blocking Stat3 signaling. While EGF-R kinase activity is not required for constitutive Stat3 activation in breast cancer cells, EGF stimulation further increases STAT DNA-binding activity, consistent with an important role for EGF-R in STAT signaling and malignant progression. Analysis of primary breast tumor specimens from patients with advanced disease revealed that the majority exhibit elevated STAT DNA-binding activity compared to adjacent non-tumor tissues. Our findings, taken together, suggest that tyrosine kinases transduce signals through Stat3 protein that contribute to the growth and survival of human breast cancer cells in culture and potentially in vivo.

Personality predictors of citizenship performance

Abstract: This article briefly introduces the criterion construct, citizenship performance, describes how this construct is different from task performance and presents a recently derived 3-dimension model of the domain. Evidence is then reviewed for links between personality constructs and citizenship performance. An update of the Organ and Ryan (1995) meta-analysis of personality-organizational citizenship behavior relationships suggests slightly higher correlations than those found in the meta-analysis and also indicates that personality, at least the conscientiousness and dependability constructs, correlates more highly with citizenship performance than with task performance. These results are discussed in the broader context of building models of job performance and studying linkages between individual differences and relatively specific criterion constructs.

Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression

Abstract: Large granular lymphocyte (LGL) leukemia is characterized by the expansion of antigen-activated cytotoxic T lymphocytes. These leukemic cells are resistant to Fas-mediated apoptosis despite expressing high levels of Fas. We found that leukemic LGL from 19 patients displayed high levels of activated STAT3. Treatment of leukemic LGL with the JAK-selective tyrosine kinase inhibitor AG-490 induced apoptosis with a corresponding decrease in STAT-DNA binding activity. Moreover, using an antisense oligonucleotide approach to diminish STAT3 expression, we found that Fas sensitivity was restored in leukemic LGL. AG-490–induced apoptosis in leukemic LGL was independent of Bcl-xL or Bcl-2 expression. However, we found that the Bcl-2–family protein Mcl-1 was significantly reduced by AG-490 treatment. Activated STAT3 was shown to bind an SIE-related element in the murine mcl-1 promoter. Using a luciferase reporter assay, we demonstrated that v-src overexpression in NIH3T3 induced STAT3-dependent transcriptional activity from the mcl-1 promoter and increased endogenous Mcl-1 protein levels. We conclude that STAT3 activation contributed to accumulation of the leukemic LGL clones. These findings suggest that investigation should focus on novel strategies targeting STAT3 in the treatment of LGL leukemia.

Mechanism of Immune Dysfunction in Cancer Mediated by Immature Gr-1+ Myeloid Cells

Abstract: The mechanism of tumor-associated T cell dysfunction remains an unresolved problem of tumor immunology. Development of T cell defects in tumor-bearing hosts are often associated with increased production of immature myeloid cells. In tumor-bearing mice, these immature myeloid cells are represented by a population of Gr-1+ cells. In this study we investigated an effect of these cells on T cell function. Gr-1+ cells were isolated from MethA sarcoma or C3 tumor-bearing mice using cell sorting. These Gr-1+ cells expressed myeloid cell marker CD11b and MHC class I molecules, but they lacked expression of MHC class II molecules. Tumor-induced Gr-1+ cells did not affect T cell responses to Con A and to a peptide presented by MHC class II. In sharp contrast, Gr-1+ cells completely blocked T cell response to a peptide presented by MHC class I in vitro and in vivo. Block of the specific MHC class I molecules on the surface of Gr-1+ cells completely abrogated the observed effects of these cells. Thus, immature myeloid cells specifically inhibited CD8-mediated Ag-specific T cell response, but not CD4-mediated T cell response. Differentiation of Gr-1+ cells in the presence of growth factors and all-trans retinoic acid completely eliminated inhibitory potential of these cells. This may suggest a new approach to cancer treatment.

Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer

Abstract: Purpose: A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address ( 1 ) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); ( 2 ) the impact of accelerating PORT using a concomitant boost schedule; and ( 3 ) the importance of the overall combined treatment duration on the treatment outcome. Methods and Materials: Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group ( n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group ( n = 31); and, by random assignment, 63 Gy during 5 weeks ( n = 76) or 7 weeks ( n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity. Results: Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features ( p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC ( p = 0.03) and survival ( p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC ( p = 0.005) and survival ( p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity. Conclusions: This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT.

Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis

Abstract: Signal transducer and activator of transcription (STAT) proteins perform key roles in mediating signaling by cytokines and growth factors, including platelet-derived growth factor (PDGF). In addition, Src family kinases activate STAT signaling and are required for PDGF-induced mitogenesis in normal cells. One STAT family member, Stat3, has been shown to have an essential role in cell transformation by the Src oncoprotein. However, the mechanisms by which STAT-signaling pathways contribute to mitogenesis and transformation are not fully defined. We show here that disruption of Stat3 signaling by using dominant-negative Stat3β protein in NIH 3T3 fibroblasts suppresses c-Myc expression concomitant with inhibition of v-Src-induced transformation. Ectopic expression of c-Myc is able to partially reverse this inhibition, suggesting that c-Myc is a downstream effector of Stat3 signaling in v-Src transformation. Furthermore, c-myc gene knockout fibroblasts are refractory to transformation by v-Src, consistent with a requirement for c-Myc protein in v-Src transformation. In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3β protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression. Moreover, inhibition of Src family kinases with the pharmacologic agent, SU6656, blocks Stat3 activation by PDGF. These findings, combined together, delineate the signaling pathway, PDGF → Src → Stat3 → Myc, that is important in normal PDGF-induced mitogenesis and subverted in Src transformation.

Narrative's Virtues

Abstract: Reacting to the charge that personal narratives, especially illness narratives, constitute a “blind alley” that misconstrues the essential nature of narrative by substituting a therapeutic for a sociological view of the person, this article speaks back to critics who regard narratives of suffering as privileged, romantic, and/or hyperauthentic. The author argues that this critique of personal narrative rests on an idealized and discredited theory of inquiry, a monolithic conception of ethnographic inquiry, a distinctly masculine characterization of sociology, and a veiled resistance to the moral, political, existential, and therapeutic goals of this work. Layering his responses to the critique with brief personal stories regarding the suppressed emotionality that motivates academics to oppose innovations, the author examines his own motives as well as those of the critics, concluding that multiplicity is easier to pronounce than to live and urging a commitment to a social science that can accommodate dive...

AKT1/PKBα Kinase Is Frequently Elevated in Human Cancers and Its Constitutive Activation Is Required for Oncogenic Transformation in NIH3T3 Cells

Abstract: Extensive studies have demonstrated that the Akt/AKT1 pathway is essential for cell survival and inhibition of apoptosis; however, alterations of Akt/AKT1 in human primary tumors have not been well documented. In this report, significantly increased AKT1 kinase activity was detected in primary carcinomas of prostate (16 of 30), breast (19 of 50), and ovary (11 of 28). The results were confirmed by Western blot and immunohistochemical staining analyses with phospho-Ser473 Akt antibody. The majority of AKT1-activated tumors are high grade and stage III/lV (13 of 16 prostate, 15 of 19 breast, and 8 of 11 ovarian carcinomas). Previous studies showed that wild-type AKT1 was unable to transform NIH3T3 cells. To demonstrate the biological significance of AKT1 activation in human cancer, constitutively activated AKT1 (Myr-Akt) was introduced into NIH3T3 cells. Overexpression of Myr-Akt in the stably transfected cells resulted in malignant phenotype, as determined by growth in soft agar and tumor formation in nude mice. These data indicate that AKT1 kinase, which is frequently activated in human cancer, is a determinant in oncogenesis and a potential target for cancer intervention.

Marimastat as First-Line Therapy for Patients With Unresectable Pancreatic Cancer: A Randomized Trial

Abstract: PURPOSE: The prognosis for unresectable pancreatic cancer remains dismal (1-year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer performed to date, compares marimastat, the first of a new class of agents, with gemcitabine. PATIENTS AND METHODS: Four hundred fourteen patients with unresectable pancreatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m2. The primary end point was survival. Progression-free survival, patient benefit, and safety were also assessed. RESULTS: There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P = .19). Median survival times were 111, 105, 125, and 167 days, respectively, and 1-year survival rates were 14%, 14%, 20%, and 19%, respectively. There was a significant difference in survival rates between patients treated with...

Regulation of Transcription Factor YY1 by Acetylation and Deacetylation

Abstract: YY1 is a sequence-specific DNA-binding transcription factor that has many important biological roles. It activates or represses many genes during cell growth and differentiation and is also required for the normal development of mammalian embryos. Previous studies have established that YY1 interacts with histone acetyltransferases p300 and CREB-binding protein (CBP) and histone deacetylase 1 (HDAC1), HDAC2, and HDAC3. Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs. YY1 was acetylated in two regions: both p300 and PCAF acetylated the central glycine-lysine-rich domain of residues 170 to 200, and PCAF also acetylated YY1 at the C-terminal DNA-binding zinc finger domain. Acetylation of the central region was required for the full transcriptional repressor activity of YY1 and targeted YY1 for active deacetylation by HDACs. However, the C-terminal region of YY1 could not be deacetylated. Rather, the acetylated C-terminal region interacted with HDACs, which resulted in stable HDAC activity associated with the YY1 protein. Finally, acetylation of the C-terminal zinc finger domain decreased the DNA-binding activity of YY1. Our findings suggest that in the natural context, YY1 activity is regulated through intricate mechanisms involving negative feedback loops, histone deacetylation, and recognition of the cognate DNA sequence affected by acetylation and deacetylation of the YY1 protein.

The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change

Abstract: The serine-threonine kinase Akt exerts its anti-apoptotic effects through several downstream targets, including the pro-apoptotic Bc1-2 family member Bad, Forkhead transcription factors, and the cyclic AMP response element-binding protein (CREB). In this report we demonstrate that Akt inhibits a conformational change in the pro-apoptotic Bax protein and its translocation to mitochondria, thus preventing the disruption of the mitochondrial inner membrane potential (DeltaPsi(m)), caspase-3 activation, and apoptosis in pre-B hematopoietic cells FL5.12 following interleukin-3 (IL-3) withdrawal. Inhibition of PI-3 kinase, but not MAPK kinase, promotes this conformational change in Bax. Moreover, overexpression of Akt suppresses the relocalization of GFP-Bax to mitochondria and apoptosis in Hela cells induced by the DNA-damaging agent methyl methanesulphonate. However, Akt does not abolish the ability of a conformationally changed Bax mutant, GFP-Bax (DeltaS184), to translocate to mitochondria and to induce apoptosis. These findings indicate that Akt exerts its anti-apoptotic effects in cells at a premitochondrial stage, at least in part, by inhibiting Bax conformational change and its redistribution to the mitochondrial membranes.

Malignant MCF10CA1 Cell Lines Derived from Premalignant Human Breast Epithelial MCF10AT Cells

Abstract: The MCF10 series of cell lines was derived from benign breast tissue from a woman with fibrocystic disease The MCF10 human breast epithelial model system consists of mortal MCF10M and MCF10MS (mortal cells grown in serum-free and serum-containing media, respectively), immortalized but otherwise normal MCF10F and MCF10A lines (free-floating versus growth as attached cells), transformed MCF10AneoT cells transfected with T24 Ha-ras, and premalignant MCF10AT cells with potential for neoplastic progression The MCF10AT, derived from xenograft-passaged MCF10-AneoT cells, generates carcinomas in ∼25% of xenografts We now report the derivation of fully malignant MCF10CA1 lines that complete the spectrum of progression from relatively normal breast epithelial cells to breast cancer cells capable of metastasis MCF10CA1 lines display histologic variations ranging from undifferentiated carcinomas, sometimes with focal squamous differentiation, to well-differentiated adenocarcinomas At least two metastasize to the lung following injection of cells into the tail vein; one line grows very rapidly in the lung, with animals moribund within 4 weeks, whereas the other requires 15 weeks to reach the same endpoint In addition to variations in efficiency of tumor production, the MCF10CA1 lines show differences in morphology in culture, anchorage-independent growth, karyotype, and immunocytochemistry profiles The MCF10 model provides a unique tool for the investigation of molecular changes during progression of human breast neoplasia and the generation of tumor heterogeneity on a common genetic background

Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K.

Abstract: We have shown previously that the AKT2 pathway is essential for cell survival and important in malignant transformation. In this study, we demonstrate elevated kinase levels of AKT2 and phosphatidylinositol-3-OH kinase (PI3K) in 32 of 80 primary breast carcinomas. The majority of the cases with the activation are estrogen receptor alpha (ERalpha) positive, which prompted us to examine whether AKT2 regulates ERalpha activity. We found that constitutively activated AKT2 or AKT2 activated by epidermal growth factor or insulin-like growth factor-1 promotes the transcriptional activity of ERalpha. This effect occurred in the absence or presence of estrogen. Activated AKT2 phosphorylates ERalpha in vitro and in vivo, but it does not phosphorylate a mutant ERalpha in which ser-167 was replaced by Ala. The PI3K inhibitor, wortmannin, abolishes both the phosphorylation and transcriptional activity of ERalpha induced by AKT2. However, AKT2-induced ERalpha activity was not inhibited by tamoxifen but was completely abolished by ICI 164,384, implicating that AKT2-activated ERalpha contributes to tamoxifen resistance. Moreover, we found that ERalpha binds to the p85alpha regulatory subunit of PI3K in the absence or presence of estradiol in epithelial cells and subsequently activates PI3K/AKT2, suggesting ERalpha regulation of PI3K/AKT2 through a nontranscriptional and ligand-independent mechanism. These data indicate that regulation between the ERalpha and PI3K/AKT2 pathway (ERalpha-PI3K/AKT2-ERalpha) may play an important role in pathogenesis of human breast cancer and could contribute to ligand-independent breast cancer cell growth.

Self-Assembly of Nanometer-Scale Secondary Building Units into an Undulating Two-Dimensional Network with Two Types of Hydrophobic Cavity

Abstract: A series of bowls separated by hour-glass-shaped channels characterizes the structure of the undulating two-dimensional coordination polymer that is prepared from a nanoscale secondary building unit (nSBU), which is formed by four square metal(II)carboxylate SBUs that have 1,3-benzenedicarboxylate units as 120° spacers

Market Reaction to ERP Implementation Announcements

Abstract: The objective of this research is to examine how the capital market responds when a firm announces that it plans to implement an enterprise resource planning (ERP) system. This is the first study t...