171 research outputs found
Differences in Characteristics of Criminal Behavior Between Solo and Team Serial Killers
Criminal Profiling and classification of serial killers has been an expanding area of research for decades. Recent research has called into question the accuracy and utility of these systems, and calls for further research and development. This study aims to use the Serial Killer Database (SKDB) to examine and classify differences in criminal behavior between serial killers who act alone versus those who act in pairs, groups, or teams. The specific aim of this study is to examine whether there are significant differences between Solo Serial Killers and Team Serial Killers in the Number of Victims, Length of Career, Method of Killing, Motive for Killing, and Relationship to the Victim. From the SKDB, a total of 4,865 serial killers will be included in either the Solo Killer (n=3,806) or the Team Killer (n=1,059) groups. Using cluster analysis, differences in the above variables were examined across groups, in an effort to detect meaningful and predictable patterns that may differentiate the two groups. The purpose of this study was to add to the expanding research on serial killer typologies and classifications, and to provide support for furthering the specificity of existing typologies to include differentiating between Solo and Team Killers
Sensitivity and Specificity of Sex for Detecting Differences in the Kinetics of Depth Jumps Performed by NCAA Athletes
It is well established that female athletes have a greater incidence of lower extremity injuries when compared to males of the same sport. There is interest in using the depth jump as a practical screen for lower extremity injury risk, however, prior research is inconclusive. There is evidence that males and females tend to adopt distinct motor strategies when anticipating and reacting to the landing impact phase of depth jumping. From this, it is reasonable to expect that depth jump kinetics are influenced by sex, yet there is a need for comprehensive analysis. Gaining a better understanding of which kinetic variables are most specific and sensitive to sex could improve the efficacy of using the depth jump as an injury risk screen. Thus, the purpose of this investigation was to evaluate the sensitivity and specificity of sex for detecting differences in the kinetics of depth jumps performed by NCAA Division I basketball athletes. Twenty NCAA Division I basketball athletes (male n = 9, female n = 11; 19.9 Âą 1.1 years; 82.6 Âą 13.9 kg; 188.6 Âą 11.3 cm) volunteered to participate in this investigation. Participants performed 3 trials of depth jumping from drop heights of 0.51, 0.66, and 0.81m. For each trial, vertical ground reaction Forces were captured using a tri-axial Force platform. Dependent measures were estimated from Force data and included peak Force, rate of Force development, peak Force reduction, jump height, ground contact time, and the reactive strength index. The sensitivity and specificity of sex for detecting differences in dependent measures were evaluated using receiver operating curve analyses. The area under the curve for dependent measures ranged from 0.51 to 0.98. The area under the curve for jump height (0.81m DJ) was statistically significant (p \u3c 0.001). The area under the curve for all other dependent measures was not statistically significant (p =0.08 â 1.00). Although the sample size in the present investigation was not sufficient for detecting variable specificity and sensitivity to sex, the findings may support further research and application of the depth jump as a tool to screen for lower extremity injury risk in competitive athletes. Presentation Time: Thursday, 9-10 a.m
The Role of Helicobacter pylori in Peptic Ulcer Disease
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90299/1/j.1875-9114.1993.tb02740.x.pd
Integrating a Spiritual Care Model within an Accelerated Nursing Curriculum
Creighton University College of Nursing (CON), consistent with the University mission, focuses on the unique journey of each student to seek the truths and values essential to a fulfilling human life. Inspired by this mission, the faculty of the CON decided to integrate spirituality into the one-year accelerated nursing curriculum (ANC). The diversity of the student population, along with the rigor and intensity of the program, required collaboration among nursing faculty to accomplish the integration. The ANC Integrated Spirituality Model was developed and used as an organizing framework. This model integrates the Creighton University College of Nursing selected Ignatian values as the foundation. Specific student activities involving spirituality and reflective practice were identified for each of the three semesters of the ANC to promote leveling of the student learning activities. The establishment of a reflective practice was identified to envelop the organizing framework and provide a critical tangible proficiency for support and evaluation of the integration of spirituality across the ANC curriculum and an ongoing resource for future nursing practice
6â˛,7â˛âDihydroxybergamottin in grapefruit juice and Seville orange juice: Effects on cyclosporine disposition, enterocyte CYP3A4, and Pâglycoprotein
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109869/1/cptclpt1999363.pd
Transcriptional Activity of the Islet β Cell Factor Pdx1 is Augmented by Lysine Methylation Catalyzed by the Methyltransferase Set7/9
The transcription factor Pdx1 is crucial to islet β cell function and regulates target genes in part through interaction with coregulatory factors. Set7/9 is a Lys methyltransferase that interacts with Pdx1. Here we tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Using mass spectrometry and mutational analysis of purified proteins, we found that Set7/9 methylates the N-terminal residues Lys-123 and Lys-131 of Pdx1. Methylation of these residues occurred only in the context of intact, full-length Pdx1, suggesting a specific requirement of secondary and/or tertiary structural elements for catalysis by Set7/9. Immunoprecipitation assays and mass spectrometric analysis using β cells verified Lys methylation of endogenous Pdx1. Cell-based luciferase reporter assays using wild-type and mutant transgenes revealed a requirement of Pdx1 residue Lys-131, but not Lys-123, for transcriptional augmentation by Set7/9. Lys-131 was not required for high-affinity interactions with DNA in vitro, suggesting that its methylation likely enhances post-DNA binding events. To define the role of Set7/9 in β cell function, we generated mutant mice in which the gene encoding Set7/9 was conditionally deleted in β cells (SetÎβ). SetÎβ mice exhibited glucose intolerance similar to Pdx1-deficient mice, and their isolated islets showed impaired glucose-stimulated insulin secretion with reductions in expression of Pdx1 target genes. Our results suggest a previously unappreciated role for Set7/9-mediated methylation in the maintenance of Pdx1 activity and β cell function
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm
Background: Polyamine metabolism has a critical role in cell death and proliferation representing a potential
target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and
its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in
anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO
enzyme.
Methods: BC tissue samples were analyzed for SMO transcript level and SMO activity. Studentâs t test was applied
to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling
analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed
by in vitro experiments, were examined.
Results: Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples
compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their
inhibition properties showed that both were good inhibitors.
Conclusions: This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a
remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition
properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials
The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme
Deregulated polyamine biosynthesis is emerging as a common feature of neuroblastoma and drugs targeting this metabolic pathway such as DFMO are in clinical and preclinical development. The polyamine analog verlindamycin inhibits the polyamine biosynthesis pathway enzymes SMOX and PAOX, as well as the histone demethylase LSD1. Based on our previous research in acute myeloid leukemia (AML), we reasoned verlindamycin may also unblock neuroblastoma differentiation when combined with all-trans-retinoic acid (ATRA). Indeed, co-treatment with verlindamycin and ATRA strongly induced differentiation regardless of MYCN status, but in MYCN-expressing cells, protein levels were strongly diminished. This process was not transcriptionally regulated but was due to increased degradation of MYCN protein, at least in part via ubiquitin-independent, proteasome-dependent destruction. Here we report that verlindamycin effectively induces the expression of functional tumor suppressorâantizyme via ribosomal frameshifting. Consistent with previous results describing the function of antizyme, we found that verlindamycin treatment led to the selective targeting of ornithine decarboxylase (the rate-limiting enzyme for polyamine biosynthesis) as well as key oncoproteins, such as cyclin D and Aurora A kinase. Retinoid-based multimodal differentiation therapy is one of the few interventions that extends relapse-free survival in MYCN-associated high-risk neuroblastoma and these results point toward the potential use of verlindamycin in this regimen.Output Status: Forthcoming/Available Onlin
Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase
Helicobacter pylori infection causes gastric cancer, the third leading cause of cancer death worldwide. More than half of the worldâs population is infected, making universal eradication impractical. Clinical trials suggest that antibiotic treatment only reduces gastric cancer risk in patients with non-atrophic gastritis (NAG), and is ineffective once preneoplastic lesions of multifocal atrophic gastritis (MAG) and intestinal metaplasia (IM) have occurred. Therefore, additional strategies for risk stratification and chemoprevention of gastric cancer are needed. We have implicated polyamines, generated by the rate-limiting enzyme ornithine decarboxylase (ODC), in gastric carcinogenesis. During H. pylori infection, the enzyme spermine oxidase (SMOX) is induced, which generates hydrogen peroxide from the catabolism of the polyamine spermine. Herein, we assessed the role of SMOX in the increased gastric cancer risk in Colombia associated with the Andean mountain region when compared with the low-risk region on the Pacific coast. When cocultured with gastric epithelial cells, clinical strains of H. pylori from the high-risk region induced more SMOX expression and oxidative DNA damage, and less apoptosis than low-risk strains. These findings were not attributable to differences in the cytotoxin-associated gene A oncoprotein. Gastric tissues from subjects from the high-risk region exhibited greater levels of SMOX and oxidative DNA damage by immunohistochemistry and flow cytometry, and this occurred in NAG, MAG and IM. In Mongolian gerbils, a prototype colonizing strain from the high-risk region induced more SMOX, DNA damage, dysplasia and adenocarcinoma than a colonizing strain from the low-risk region. Treatment of gerbils with either Îą-difluoromethylornithine, an inhibitor of ODC, or MDL 72527 (N[superscript 1,]N[superscript 4]-Di(buta-2,3-dien-1-yl)butane-1,4-diamine dihydrochloride), an inhibitor of SMOX, reduced gastric dysplasia and carcinoma, as well as apoptosis-resistant cells with DNA damage. These data indicate that aberrant activation of polyamine-driven oxidative stress is a marker of gastric cancer risk and a target for chemoprevention.National Institutes of Health (U.S.) (Grant P01CA028842)Vanderbilt Digestive Disease Center (Grant P30DK058404
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