Gene Expression and DNA Methylation in Human Papillomavirus Positive and Negative Head and Neck Squamous Cell Carcinomas

High-risk human papillomaviruses (HPV) are important agents, responsible for a large percentage of the 745,000 cases of head and neck squamous cell carcinomas (HNSCC), which were identified worldwide in 2020. In addition to being virally induced, tobacco and heavy alcohol consumption are believed to cause DNA damage contributing to the high number of HNSCC cases. Gene expression and DNA methylation differ between HNSCC based on HPV status. We used publicly available gene expression and DNA methylation profiles from the Cancer Genome Atlas and compared HPV positive and HPV negative HNSCC groups. We used differential gene expression analysis, differential methylation analysis, and a combination of these two analyses to identify the differences. Differential expression analysis identified 1854 differentially expressed genes, including PCNA, TNFRSF14, TRAF1, TRAF2, BCL2, and BIRC3. SYCP2 was identified as one of the top deregulated genes in the differential methylation analysis and in the combined differential expression and methylation analyses. Additionally, pathway and ontology analyses identified the extracellular matrix and receptor interaction pathway as the most altered between HPV negative and HPV positive HNSCC groups. Combining gene expression and DNA methylation can help in elucidating the genes involved in HPV positive HNSCC tumorigenesis, such as SYCP2 and TAF7L.     

Reference Gene Selection for Gene Expression Analyses in Mouse Models of Acute Lung Injury

qRT-PCR still remains the most widely used method for quantifying gene expression levels, although newer technologies such as next generation sequencing are becoming increasingly popular. A critical, yet often underappreciated, problem when analysing qRT-PCR data is the selection of suitable reference genes. This problem is compounded in situations where up to 25% of all genes may change (e.g., due to leukocyte invasion), as is typically the case in ARDS. Here, we examined 11 widely used reference genes for their suitability in commonly used models of acute lung injury (ALI): ventilator-induced lung injury (VILI), in vivo and ex vivo, lipopolysaccharide plus mechanical ventilation (MV), and hydrochloric acid plus MV. The stability of reference gene expression was determined using the NormFinder, BestKeeper, and geNorm algorithms. We then proceeded with the geNorm results because this is the only algorithm that provides the number of reference genes required to achieve normalisation. We chose interleukin-6 (Il-6) and C-X-C motif ligand 1 (Cxcl-1) as the genes of interest to analyse and demonstrate the impact of inappropriate normalisation. Reference gene stability differed between the ALI models and even within the subgroup of VILI models, no common reference gene index (RGI) could be determined. NormFinder, BestKeeper, and geNorm produced slightly different, but comparable results. Inappropriate normalisation of Il-6 and Cxcl1 gene expression resulted in significant misinterpretation in all four ALI settings. In conclusion, choosing an inappropriate normalisation strategy can introduce different kinds of bias such as gain or loss as well as under- or overestimation of effects, affecting the interpretation of gene expression data.     

Child custody resolution: A study of social science involvement and impact.

To explore the use of mental health professional expertise in the legal system, legal professionals' sources of social science information, and the legal profession's perspectives on the appropriate roles of mental health professionals in the process, we solicited information from attorneys and judges on (a) the extent to which they actively seek the involvement of mental health professionals in child custody cases, (b) the factors that influence such involvement, and (c) the degree to which these attitudes and practices are influenced by social science data or theory. Among the most striking features of these results was the report by the overwhelming majority of legal professionals that they did not consider either social science data or mental health professionals' involvement or recommendations in child custody cases as critical to their practice of family law. Specifically, mental health participation was rarely solicited, and when it was, this decision rested primarily on the paradigmatic regularities of the legal system or practical needs of the case rather than on a view that such involvement was central to the client's or child's mental health. The implications of these findings for collaboration between the mental health and legal disciplines in the area of family policy are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraligand cooperation in metal‐ion binding by immobilized ligands: The effect of bifunctionality

Intraligand cooperation between carbonyl and phosphoryl moieties in ion bonding was studied by the synthesis of β‐ketophosphonic acid (βkPh), phosphonoacetic acid (PhAc), and phosphonic acid (Ph) resins. A subsequent reaction gave bifunctional analogues with sulfonic acid as an additional ligand (βkPh_s, PhAc_s, and Ph_s resins). Ionic affinities were quantified with dilute solutions of Cu(II), Cd(II), and Pb(II) in 0.10M HNO₃. The effect of an increased solution ionic strength was studied with a second set of 0.10M HNO₃/0.04M NaNO₃ solutions. The results from the monofunctional resins and nitric acid alone showed that βkPh had the highest metal‐ion affinities, whereas PhAc had affinities similar to those of Ph. Comparing βkPh to Ph led to the conclusion that the carbonyl group was a strong contributor to binding through intraligand cooperation with the phosphoryl group, whereas comparing PhAc to Ph led to the conclusion that the carbonyl group played no role in the ion binding. These opposing conclusions were reconciled as follows: (1) the extent of complexation from the 0.10M HNO₃ solutions increased significantly when the monofunctional resins were sulfonated and (2) a comparison of the results for the monofunctional resins when contacting Cu(II), Cd(II), and Pb(II) in the absence of NaNO₃ with those for the bifunctional resins when contacting those ions in the presence of NaNO₃ showed that the ionic affinities were comparable for Ph and Ph_s, greater for PhAc_s than for PhAc, and comparable for βkPh_s and βkPh. The resins PhAc_s and βkPh displayed comparable ionic affinities that were higher than that of Ph. The results were consistent with the conclusion that, in the monofunctional resin, the affinity of the phosphonoacetate ligand for the metal ions was reduced because of intraligand hydrogen bonding. Intraligand cooperation was, therefore, an important variable in enhancing the metal‐ion affinities, but its effect could be attenuated by intraligand hydrogen bonding. This attenuation could be eliminated by the introduction of a highly hydrophilic group into the matrix. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 463–468, 2004     

Revisiting the Factor Structure of the Questionnaire on Smoking Urges.

This study assessed the factor structure of the Questionnaire on Smoking Urges (QSU), a commonly used assessment of cravings for cigarettes, with a sample of smokers presenting for treatment in a smoking cessation trial. On the basis of previous research, three confirmatory factor analytic models were tested. Model 1 hypothesized a 26-item, 2-factor model using the items reported in the original QSU analysis by S. T. Tiffany and D. J. Drobes (1991). Model 2 hypothesized a 12-item, 2-factor model comprised of the 6 most robust items found in each of the 2 factors of the original factor analysis. Using the 12 items from Model 2, Model 3 hypothesized a 12-item, 1-factor model. The 2nd model was found to fit the data best. Reliability was also tested using values obtained in this 2nd model, and these estimates were found to be reasonably good. Future research directions for the QSU are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concepts,methods, and languages for building timely intelligent systems

We describe the ABE/RT toolkit—a set of design, development, and experimentation tools for building time-stressed intelligent systems-and its use for the Lockheed Pilot's Associate application. We use the termtimely systems to refer to systems with hard real-time requirements for interacting with a human operator or other agents with similar time-scales. The ABE/RT methodology is based on a philosophy of rigorous engineering design in which the application developer works to guarantee the system's timeliness by identifying the various events which require timely responses, determining the worst-case frequencies of these events and the deadlines and durations of the tasks that respond to the events, and then verifying that the run-time system has enough processing resources to complete all mandatory taks by their deadlines. We believe this is the only way in the near-term to build complex real-time intelligent systems that will be reliable enough for critical applications with demanding users. The ABE/RT Toolkit contains a set of languages for specifying the structure and behavior of timely systems, together with tools to simulate those models, log and analyze data collected during simulation runs, predict an application's performance on a specified target hardware architecture, and deploy the application on the target architecture.This research was partially funded by the Defense Advanced Research Projects Agency, 1400 Wilson Blvd., Arlington, VA 22209, under contracts F30602-85-C-0135 and F33615-85-C-3804, administered by the Air Force Systems Command, Rome Air Development Center and the Air Force Cockpit Technology Directorate, Wright Research and Development Center, respectively. Use of this material, including copying, by the U.S. government is permitted in accordance with the terms of those contracts.     

PARTICIPATION IN COMMUNITY WATCH PROGRAMS

Community watch programs are spreading rapidly across the country. Based on a sample of residents in five SMSAs, this study addresses the questions: Who is aware of these programs in their local area? Who is participating in these programs? Why are they participating? The results indicate that those with higher incomes and those who are integrated into their community are more likely to be aware of community watch programs. Participation in these programs, similar to participation in general purpose community organizations, is related to income, race and the perceived effectiveness of the courts. The results provide evidence for two models of why people participate in community watch: the community responsibility model and the property protection model. Two other models, the lack of confidence in the criminal justice system model and the fear model were not supported by the data.     

Age and skill in visual search.

The effects of age and experience on visual-cognitive performance were examined by administering a domain-relevant visual search task and a standard letter search task to skilled and control Ss at 2 age levels (young and middle-aged adults). In the skilled task, Ss searched for a designated item within 3-item displays using images of bacteria morphology as targets and distractors. Each target was preceded by a word prime representative of bacteria morphology that was valid, invalid, or neutral with respect to the diagnostic characteristics of the target. Skilled Ss showed an age deficit in letter search performance, but the performance of the young and middle-aged skilled Ss was not different on the domain-relevant task. Valid primes produced benefits for the young and middle-aged skilled participants, whereas control Ss were unaffected by the prime manipulation. Results were consistent with the prediction that experience serves to attenuate age-related declines in visual-cognitive performance in the skilled domain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An IS1 case: The closed loop scenario

Organizations are exploring the potential of inter-organizational information systems (IS¹s) in greater numbers. Generally the incentives are cost reduction and/or productivity improvement. Gaining these potential benefits requires cooperation within the information exchange path. Potential barriers, however, are the recognition of an information processing problem and the readiness to accept automated solutions.