bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming the insider
Authors: Willison Robert , Siponen Mikko 
Published: August 2009

Information security has become increasingly important for organizations, given their dependence on ICT. Not surprisingly, therefore, the external threats posed by hackers and viruses have received extensive coverage in the mass media. Yet numerous security surveys also point to the 'insider' threat of employee computer crime. In 2006, for example, the Global Security Survey by Deloitte reports that 28% of respondent organizations encountered considerable internal computer fraud. This figure may not appear high, but the impact of crime perpetrated by insiders can be profound. Donn Parker argues that 'cyber-criminals' should be considered in terms of their criminal attributes, which include skills, knowledge, resources, access and motives (SKRAM). It is as a consequence of such attributes, acquired within the organization, that employers can pose a major threat. Hence, employees use skills gained through their legitimate work duties for illegitimate gain. A knowledge of security vulnerabilities can be exploited, utilising resources and access are provided by companies. It may even be the case that the motive is created by the organization in the form of employee disgruntlement. These criminal attributes aid offenders in the pursuit of their criminal acts, which in the extreme can bring down an organization.
In the main, companies have addressed the insider threat through a workforce, which is made aware of its information security responsibilities and acts accordingly. Thus, security policies and complementary education and awareness programmes are now commonplace for organizations. That said, little progress has been made in understanding the insider threat from an offender's perspective. As organizations attempt to grapple with the behavior of dishonest employees, criminology potentially offers a body of knowledge for addressing this problem. It is suggested that Situational Crime Prevention (SCP), a relative newcomer to criminology, can help enhance initiatives aimed at addressing the insider threat.
In this article, we discuss how recent criminological developments that focus on the criminal act, represent a departure from traditional criminology, which examines the causes of criminality. As part of these recent developments we discuss SCP. After defining this approach, we illustrate how it can inform and enhance information security practices.
In recent years, a number of criminologists have criticised their discipline for assuming that the task of explaining the causes of criminality is the same as explaining the criminal act. Simply to explain how people develop a criminal disposition is only half the equation. What is also required is an explanation of how crimes are perpetrated. Criminological approaches, which focus on the criminal act, would appear to offer more to information security practitioners than their dispositional counterparts. Accordingly, the SCP approach can offer additional tools for practitioners in their fight against insider computer crime.
Modified agile practices for outsourced software projects
Authors: Batra Dinesh 
Published: August 2009

Frustration with the bureaucratic nature of the disciplined approach has led to the call for agile development. The new approach is defined by the Agile Manifesto (http://agilemanifesto.org/), which values individuals and interactions over processes and tools, working software over comprehensive documentation, customer collaboration over contract negotiation, and agility in responding to change over following a prescribed plan. Agile development does not focus on process improvement; instead it focuses on customer satisfaction and employee empowerment. This is evident from reading the stated values and principles of the Agile Manifesto, which include fairly extreme positions such as "welcome changing requirements, even late in development" and "the best architectures, requirements, and designs emerge from self-organizing teams."
An interesting issue arising from the call for agile development is its role in distributed development, which usually translates to offshore development. A recent study indicates that agile practices can reduce temporal, geographical, and socio-cultural distances in distributed development projects. The study researched agile development between teams located in the U.S. and Ireland, and while it reported that overall communication was improved, it also noted problems related to geographical, temporal, and even language distances. Although there are other reported successes of distributed agile development, the projects are generally small, the team members are likely familiar with each other, and the participants are largely experts or high caliber developers.
This raises a research, as well as a practical, question: can we extend the use of agile practices from small projects to medium and large projects that involve a significant outsourcing component? To address this question, we must drop constraints such as small size projects, and expert developers belonging to the same company, and examine problems arising from geographical, temporal, and cultural distances. Accordingly, agile practices may need to be modified.
In this article, the key issues of software projects with an outsourced component are first identified. These issues are then used as a background to evaluate how standard agile practices stand up when applied to larger projects. This evaluation is followed by recommendations for modified agile practices for outsourced software projects.
Identification of Novel Gene Amplifications in Breast Cancer and Coexistence of Gene Amplification with an Activating Mutation of PIK3CA
Authors: Kadota Mitsutaka , Sato Misako , Duncan Beverly , Ooshima Akira , Yang Howard H. , Diaz-Meyer Natacha , Gere Sheryl , Kageyama Shun-Ichiro , Fukuoka Junya , Nagata Takuya , Tsukada Kazuhiro , Dunn Barbara K. , Wakefield Lalage M. , Lee Maxwell P. 
Published: August 2009

Abstract
To identify genetic events that characterize cancer progression, we conducted a comprehensive genetic evaluation of 161 primary breast tumors. Similar to the “mountain-and-hill” view of mutations, gene amplification also shows high- and low-frequency alterations in breast cancers. The frequently amplified genes include the well-known oncogenes ERBB2, FGFR1, MYC, CCND1, and PIK3CA, whereas other known oncogenes that are amplified, although less frequently, include CCND2, EGFR, FGFR2, and NOTCH3. More importantly, by honing in on minimally amplified regions containing three or fewer genes, we identified six new amplified genes: POLD3, IRAK4, IRX2, TBL1XR1, ASPH, and BRD4. We found that both the IRX2 and TBL1XR1 proteins showed higher expression in the malignant cell lines MCF10CA1h and MCF10CA1a than in their precursor, MCF10A, a normal immortalized mammary epithelial cell line. To study oncogenic roles of TBL1XR1, we performed knockdown experiments using a short hairpin RNA approach and found that depletion of TBL1XR1 in MCF10CA1h cells resulted in reduction of cell migration and invasion as well as suppression of tumorigenesis in mouse xenografts. Intriguingly, our mutation analysis showed the presence of activation mutations in the PIK3CA gene in a subset of tumors that also had DNA copy number increases in the PIK3CA locus, suggesting an additive effect of coexisting activating amino acid substitution and dosage increase from amplification. Our gene amplification and somatic mutation analysis of breast primary tumors provides a coherent picture of genetic events, both corroborating and novel, offering insight into the genetic underpinnings of breast cancer progression. [Cancer Res 2009;69(18):7357–65]
Dietary Feeding of Dibenzoylmethane Inhibits Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Model
Authors: Oo Khor Tin , Yu Siwang , Barve Avanthika , Hao Xingpei , Hong Jin-Liern , Lin Wen , Foster Barbara , Huang Mou-Tuan , Newmark Harold L. , Kong Ah-Ng 
Published: August 2009

Abstract
Dibenzoylmethane (DBM), a minor β-diketone constituent of licorice, has been shown to exhibit antineoplastic effects in prostate cancer cell lines by induction of cell cycle arrest and regulation of androgen receptor expression. In the present study, we investigated the in vitro and in vivo efficacy of DBM using TRAMP-C1 cell lines and TRAMP mice. DBM was found to arrest TRAMP-C1 cells at G2-M phase of cell cycle and suppressed phosphorylated retinoblastoma, cyclin D1, and cyclin A. Importantly, DBM was found to be equally effective in suppression of prostate tumor progression in TRAMP mice. At 8 or 12 weeks of age, mice were fed control or 1% DBM-supplemented diets until 24 weeks of age. Our results show that DBM-fed groups had a lower incidence of palpable tumor and high-grade prostatic intraepithelial neoplasia. Subsequent mechanistic studies show that the expression of phosphorylated retinoblastoma, c-myc, cyclin D1, cyclin A, phosphorylated Akt, phosphorylated PDK-1, and phosphorylated S6 was significantly reduced by DBM. Our findings suggest that DBM blocks the growth and progression of prostate cancer in TRAMP mice via modulation of tumor cell cycle regulation and therefore merits its consideration for future clinical intervention of human prostate cancer. [Cancer Res 2009;69(17):7096–102]
The CHRNA5-CHRNA3-CHRNB4 Nicotinic Receptor Subunit Gene Cluster Affects Risk for Nicotine Dependence in African-Americans and in European-Americans
Authors: Saccone Nancy L. , Wang Jen C. , Breslau Naomi , Johnson Eric O. , Hatsukami Dorothy , Saccone Scott F. , Grucza Richard A. , Sun Lingwei , Duan Weimin , Budde John , Culverhouse Robert C. , Fox Louis , Hinrichs Anthony L. , Steinbach Joseph Henry , Wu Meng , Rice John P. , Goate Alison M. , Bierut Laura J. 
Published: August 2009

Abstract
Genetic association studies have shown the importance of variants in the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit gene cluster on chromosome 15q24-25.1 for the risk of nicotine dependence, smoking, and lung cancer in populations of European descent. We have carried out a detailed study of this region using dense genotyping in both European-Americans and African-Americans. We genotyped 75 known single nucleotide polymorphisms (SNPs) and one sequencing-discovered SNP in an African-American sample (N = 710) and in a European-American sample (N = 2,062). Cases were nicotine-dependent and controls were nondependent smokers. The nonsynonymous CHRNA5 SNP rs16969968 is the most significant SNP associated with nicotine dependence in the full sample of 2,772 subjects [P = 4.49 × 10−8; odds ratio (OR), 1.42; 95% confidence interval (CI), 1.25–1.61] as well as in African-Americans only (P = 0.015; OR, 2.04; 1.15–3.62) and in European-Americans only (P = 4.14 × 10−7; OR, 1.40; 1.23–1.59). Other SNPs that have been shown to affect the mRNA levels of CHRNA5 in European-Americans are associated with nicotine dependence in African-Americans but not in European-Americans. The CHRNA3 SNP rs578776, which has a low correlation with rs16969968, is associated with nicotine dependence in European-Americans but not in African-Americans. Less common SNPs (frequency ≤ 5%) are also associated with nicotine dependence. In summary, multiple variants in this gene cluster contribute to nicotine dependence risk, and some are also associated with functional effects on CHRNA5. The nonsynonymous SNP rs16969968, a known risk variant in populations of European-descent, is also significantly associated with risk in African-Americans. Additional SNPs contribute to risk in distinct ways in these two populations. [Cancer Res 2009;69(17):6848–56]
Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer
Authors: Stern Mariana C. , Lin Jie , Figueroa Jonine D. , Kelsey Karl T. , Kiltie Anne E. , Yuan Jian-Min , Matullo Giuseppe , Fletcher Tony , Benhamou Simone , Taylor Jack A. , Placidi Donatella , Zhang Zuo-Feng , Steineck Gunnar , Rothman Nathaniel , Kogevinas Manolis , Silverman Debra , Malats Nuria , Chanock Stephen , Wu Xifeng , Karagas Margaret R. , Andrew Angeline S. , Nelson Heather H. , Bishop D. Timothy , Sak Sei Chung , Choudhury Ananya , Barrett Jennifer H. , Elliot Faye , Corral Román , Joshi Amit D. , Gago-Dominguez Manuela , Cortessis Victoria K. , Xiang Yong-Bing , Gao Yu-Tang , Vineis Paolo , Sacerdote Carlotta , Guarrera Simonetta , Polidoro Silvia , Allione Alessandra , Gurzau Eugen , Koppova Kvetoslava , Kumar Rajiv , Rudnai Peter , Porru Stefano , Carta Angela , Campagna Marcello , Arici Cecilia , Park Sung Shim Lani , Garcia-Closas Montserrat ,   for the International Consortium of Bladder Cancer
Published: August 2009

Abstract
Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01–1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01–1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00–1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. [Cancer Res 2009;69(17):6857–64]
c-Jun NH2-Terminal Kinase Activation Is Essential for DRAM-Dependent Induction of Autophagy and Apoptosis in 2-Methoxyestradiol–Treated Ewing Sarcoma Cells
Authors: Lorin Séverine , Borges Amélie , Ribeiro Dos Santos Lisandra , Souquère Sylvie , Pierron Gérard , Ryan Kevin M. , Codogno Patrice , Djavaheri-Mergny Mojgan 
Published: August 2009

Abstract
Ewing sarcoma and osteosarcoma are two aggressive cancers that affect bones and soft tissues in children and adolescents. Despite multimodal therapy, patients with metastatic sarcoma have a poor prognosis, emphasizing a need for more effective treatment. We have shown previously that 2-methoxyestradiol (2-ME), an antitumoral compound, induces apoptosis in Ewing sarcoma cells through c-Jun NH2-terminal kinase (JNK) activation. In the present study, we provide evidence that 2-ME elicits macroautophagy, a process that participates in apoptotic responses, in a JNK-dependent manner, in Ewing sarcoma and osteosarcoma cells. We also found that the enhanced activation of JNK by 2-ME is partially regulated by p53, highlighting the relationship of JNK and autophagy to p53 signaling pathway. Furthermore, we showed that 2-ME up-regulates damage-regulated autophagy modulator (DRAM), a p53 target gene, in Ewing sarcoma cells through a mechanism that involves JNK activation. The silencing of DRAM expression reduced both apoptosis and autophagy triggered by 2-ME in Ewing sarcoma and osteosarcoma cells. Our results therefore identify JNK as a novel mediator of DRAM regulation. These findings suggest that 2-ME or other anticancer therapies that increase DRAM expression or function could be used to effectively treat sarcoma patients. [Cancer Res 2009;69(17):6924–31]
The Double-Edged Sword of Autophagy Modulation in Cancer
Authors: White Eileen , DiPaola Robert S. 
Published: August 2009

Abstract
Macroautophagy (autophagy) is a lysosomal degradation pathway for the breakdown of intracellular proteins and organelles. Although constitutive autophagy is a homeostatic mechanism for intracellular recycling and metabolic regulation, autophagy is also stress responsive, in which it is important for the removal of damaged proteins and organelles. Autophagy thereby confers stress tolerance, limits damage, and sustains viability under adverse conditions. Autophagy is a tumor-suppression mechanism, yet it enables tumor cell survival in stress. Reconciling how loss of a prosurvival function can promote tumorigenesis, emerging evidence suggests that preservation of cellular fitness by autophagy may be key to tumor suppression. As autophagy is such a fundamental process, establishing how the functional status of autophagy influences tumorigenesis and treatment response is important. This is especially critical as many current cancer therapeutics activate autophagy. Therefore, efforts to understand and modulate the autophagy pathway will provide new approaches to cancer therapy and prevention. (Clin Cancer Res 2009;15(17):5308–16)
Targeted Radiotherapy for Prostate Cancer with an Oncolytic Adenovirus Coding for Human Sodium Iodide Symporter
Authors: Hakkarainen Tanja , Rajecki Maria , Sarparanta Mirkka , Tenhunen Mikko , Airaksinen Anu J. , Desmond Renée A. , Kairemo Kalevi , Hemminki Akseli 
Published: August 2009

Abstract
Purpose: Oncolytic adenoviruses are promising tools for cancer therapy. Although several clinical reports have indicated both safety and promising antitumor capabilities for these viruses, there are only a few examples of complete tumor eradication. Thus, the antitumor efficacy of oncolytic adenoviruses needs to be improved. One potentially useful approach is combination with radiotherapy.
Experimental Design: To target systemically administered radioiodide to tumors, we created Ad5/3-Δ24-human sodium iodide symporter (hNIS), a Rb-p16 pathway selective infectivity enhanced oncolytic adenovirus encoding hNIS.
Results: Ad5/3-Δ24-hNIS replication effectively killed prostate cancer cells in vitro and in vivo. Also, the virus-mediated radioiodide uptake into prostate cancer cells in vitro and into tumors in vivo. Furthermore, Ad5/3-Δ24-hNIS with radioiodide was significantly more effective than virus alone in mice with prostate cancer xenografts.
Conclusions: These results suggest that oncolytic adenovirus-mediated targeted radiotherapy might be a potentially useful option for enhancing the efficacy or adenoviral virotherapy. (Clin Cancer Res 2009;15(17):5396–403)
Inflammatory Biomarkers and Fatigue during Radiation Therapy for Breast and Prostate Cancer
Authors: Bower Julienne E. , Ganz Patricia A. , Tao May Lin , Hu Wenhua , Belin Thomas R. , Sepah Saviz , Cole Steve , Aziz Najib 
Published: August 2009

Abstract
Purpose: Biomarkers of radiation-induced behavioral symptoms, such as fatigue, have not been identified. Studies linking inflammatory processes to fatigue in cancer survivors led us to test the hypothesis that activation of the proinflammatory cytokine network is associated with fatigue symptoms during radiation therapy for breast and prostate cancer.
Experimental Design: Individuals with early-stage breast (n = 28) and prostate cancer (n= 20) completed questionnaires and provided blood samples for determination of serum levels of interleukin 1β (IL-1β) and IL-6 at assessments conducted before, during, and after a course of radiation therapy. Serum markers of proinflammatory cytokine activity, including IL-1 receptor antagonist and C-reactive protein, were examined in a subset of participants. Random coefficient models were used to evaluate the association between changes in cytokine levels and fatigue.
Results: As expected, there was a significant increase in fatigue during radiation treatment. Changes in serum levels of inflammatory markers C-reactive protein and IL-1 receptor antagonist were positively associated with increases in fatigue symptoms (Ps &lt; 0.05), although serum levels of IL-1β and IL-6 were not associated with fatigue. These effects remained significant (Ps &lt; 0.05) in analyses controlling for potential biobehavioral confounding factors, including age, body mass index, hormone therapy, depression, and sleep disturbance.
Conclusions: Results suggest that activation of the proinflammatory cytokine network and associated increases in downstream biomarkers of proinflammatory cytokine activity are associated with fatigue during radiation therapy for breast and prostate cancer.(Clin Cancer Res 2009;15(17):5534–40)
The Importance of Protein Kinase A in Prostate Cancer: Relationship to Patient Outcome in Radiation Therapy Oncology Group Trial 92-02
Authors: Pollack Alan , Bae Kyounghwa , Khor Li-Yan , Al-Saleem Tahseen , Hammond M. Elizabeth , Venkatesan Varagur , Byhardt Roger W. , Asbell Sucha O. , Shipley William U. , Sandler Howard M. 
Published: August 2009

AbstractPurpose: We previously reported that protein kinase A type I (PKARIα) overexpression was predictive of outcome in prostate cancer patients treated with radiotherapy (RT) ± short-term androgen deprivation (STAD) on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Here, we attempt to verify our prior findings and test the hypothesis that the relationship of the length of AD to patient outcome is affected by PKARIα overexpression.Experimental Design: There were 313 cases in the RTOG 92-02 study cohort with available tissue and suitable staining by immunohistochemistry. Median follow-up was 10.1 years. The intensity of PKARIα staining intensity was quantified manually and by image analysis. Multivariate analyses were done for overall mortality using Cox proportional hazards models and for local failure, biochemical failure, distant metastasis, and cause-specific mortality using Fine and Gray's regression models.Results: The expression levels of PKARIα, determined by manual and image analysis, were strongly correlated (P &lt; 0.0001). In the multivariate analyses, manual-quantified and image analysis–quantified PKARIα staining intensities were independent predictors of distant metastasis (P &lt; 0.01), local failure (P &lt; 0.05), and biochemical failure (P ≤ 0.01). Furthermore, the benefit of long-term AD over STAD was much less when PKARIα expression was high.Conclusions: PKARIα overexpression has been shown in two RTOG trials to be associated with an increased risk of failure after AD + RT. In this series of contemporary high-risk patients, PKARIα overexpression was associated with diminished response to LTAD + RT relative to STAD + RT, suggesting that such patients would be ideal for a PKARIα knockdown strategy. (Clin Cancer Res 2009;15(17):5478–84)