Perspective transformation: Women in long-term recovery from alcohol abuse

Objective. The purpose of this study was to determine the meaning of personal transformation for twenty women in long term, stable recovery from alcohol abuse; to identify themes or patterns of this recovery, and; to determine the extent to which they experienced the phenomenon of perspective transformation. ^ Method. Volunteers were recruited by advertisement, word of mouth, and through a closed circuit web based broadcast. A descriptive, exploratory study, which analyzed perspective transformation from the standpoint of five action phases, was conducted. Data was collected using in-depth personal interviews and questionnaires. Subjects' responses were analyzed by qualitative methods. Triangulation was performed on the grouped data comparing the interviews to the data produced by the questionnaires. Quantitative analysis of questionnaire items explored behavioral changes experienced before and after alcoholism recovery. ^ Results. Five phases of recovery were identified. Phase I which involved recognition that alcohol was a problem and change might be possible took several years during which 3 major transitions occurred: (1) from often being alienated to having relationships with family and friends; (2) from daily upheavals to eventually a more peaceful existence, and; (3) from denial that alcohol was a problem to acceptance and willingness to change. Recovery was often seen in a spiritual context, which also required ongoing support. During Phase II there was an assessment of self, others, and the environment which revealed a pattern of intense unhappiness and negative feelings toward self and others with a disregard for cultural norms. Phase III revealed a period of desperation as life became unmanageable, but gradual willingness to accept support and guidance and a desire to improve self and help others. This led to improvement of existing role performance and the willingness to try out new roles. In Phase IV there was a pattern of personal growth which included: the establishment of boundaries, setting priorities, a willingness to place others' needs above their own, acceptance of responsibility, and learning to cope without alcohol, often with the use of tools learned in AA. During Phase V, many experienced knowledge of frailties but growing respect for self and others, with an improved ability to function in giving relationships. Implications for Prevention and Recovery: Early education concerning addiction and recovery may play a crucial role in prevention and early recovery, as it did for children of women in this study. Recovery requires persistent effort and organized support. ^

The functions of pitx2 and Bmp signaling in craniofacial development

The formation of the vertebrate face is an extremely complex developmental process, which needs to coordinate the outgrowth of several facial primordia. Facial primordia are small buds made up of mesenchymal masses enclosed by an epithelial layer that surrounds the primitive mouth. The upper jaw is formed by the maxillary process, the lateral nasal process, and the frontonasal process while the mandibular process forms the lower jaw. Recent experiments using genetics in mice and bead implantation approaches have shown that the pitx2 homeobox gene and Bmp signaling play important roles in this complex developmental process. However, the molecular mechanisms underlying the function of pitx2 and Bmp in these events are still unclear. Here, we show that pitx2 is required for oral epithelium maintenance, and branchial arch signaling is pitx2 dosage sensitive by using pitx2 allelic combinations that encode varying levels of pitx2. Maintenance of fgf8 signaling requires only low pitx2 dosage while repression of Bmp signaling requires high pitx2 levels. Different incisor and molar phenotypes in low level pitx2 mutant embryos suggest a distinct requirement for pitx2 in tooth-type development. The results show that pitx2 is required for craniofacial muscle formation and expanded Bmp signaling results in excess bone formation in pitx2 mutant embryos. Fate-mapping studies show that ectopic bone results from excessive bone growth, instead of muscle transformation. Moreover, by using cre/loxp system we show that partial loss of Bmpr-IA in the facial primordia results in cleft lip/palate, abnormal teeth, ectopic teeth and tooth transformation. These phenotypes suggest that Bmp signaling has multiple functions during craniofacial development. The mutant palate shelves can fuse with each other when cultured in vitro, suggesting that cleft palate is secondary to the partial loss of Bmpr-IA. Furthermore, we prove that Bmp4, one of the ligands of Bmpr-IA, plays a role during lip fusion developmental process and partial loss of Bmp4 in the facial primordia results in the lip fusion delay. These results have provided insight to understand the complex signaling cascades that regulate craniofacial development. ^

Global practice experience: A useful lens for understanding patient and staff perceptions of successful integration of health information technology in primary care

Making healthcare comprehensive and more efficient remains a complex challenge. Health Information Technology (HIT) is recognized as an important component of this transformation but few studies describe HIT adoption and it's effect on the bedside experience by physicians, staff and patients. This study applied descriptive statistics and correlation analysis to data from the Patient-Centered Medical Home National Demonstration Project (NDP) of the American Academy of Family Physicians. Thirty-six clinics were followed for 26 months by clinician/staff questionnaires and patient surveys. This study characterizes those clinics as well as staff and patient perspectives on HIT usefulness, the doctor-patient relationship, electronic medical record (EMR) implementation, and computer connections in the practice throughout the study. The Global Practice Experience factor, a composite score related to key components of primary care, was then correlated to clinician and patient perspectives. This study found wide adoption of HIT among NDP practices. Patient perspectives on HIT helpfulness on the doctor-patient showed a suggestive trend that approached statistical significance (p = 0.172). Clinicians and staff noted successful integration of EMR into clinic workflow and their perception of helpfulness to the doctor-patient relationship show a suggestive increase also approaching statistical significance (p=0.06). GPE was correlated with clinician/staff assessment of a helpful doctor-patient relationship midway through the study (R 0.460, p = 0.021) with the remaining time points nearing statistical significance. GPE was also correlated to both patient perspectives of EMR helpfulness in the doctor-patient relationship (R 0.601, p = 0.001) and computer connections (R 0.618, p = 0.0001) at the start of the study. ^

Isolation and characterization of revertant cell lines expressing oncogenic rat {\it neu\/}

The neu gene encodes the transmembrane tyrosine kinase growth factor receptor, p185. To study neu induced cellular transformation, we developed revertant cells from the neu transformed NIH 3T3 cell line, B104-1-1, by treating the cells with the chemical mutagen ethylmethane sulfonate. The morphologically normal revertant cells were first selected by their ability to either attach to culture plates or survive in the presence of the cytotoxic reagents colchicine or 5-fluoro-2deoxyuridine. Two of the 21 candidate revertant cell lines isolated were further characterized and were found to lose their anchorage independence and ability to grow in 1% calf serum, indicating that they were nontransformed even though they still expressed p185 oncoprotein. The tyrosine residues of p185 in these two revertants were underphosphorylated, which may have contributed to their nontransformed status. Also, the p185 oncoprotein lacked significant tyrosine kinase activity. In addition, these revertants also resisted transformation by neu and several additional oncogenes (H-ras, N-ras, v-mos, v-abl, and v-fos) as determined by focus forming assays. These results indicated that we had successfully developed, from neu transformed cells, revertants which exhibited defective tyrosine phosphorylation and kinase activity of the neu oncoprotein. The results also suggested that neu and several other oncogenes may share common elements in their pathways for the induction of cellular transformation. ^

Biological effects of PEA3 expression in {\it HER-2\/}/{\it neu\/}-overexpressing human cancer cells and the molecular mechanisms of PEA3-mediated transcriptional repression on {\it HER-2\/}/{\it neu\/}

HER-2/neu is a receptor tyrosine kinase highly homologous with epidermal growth factor receptor. Overexpression and/or amplification of HER-2/neu has been implicated in the genesis of a number of human cancers, especially breast and ovarian cancers. Transcriptional upregulation has been shown to contribute significantly to the overexpression of this gene. Studies on the transcriptional regulation of HER-2/neu gene are important for understanding the mechanism of cell transformation and developing the therapeutic strategies to block HER-2/neu-mediated cancers. PEA3 is a DNA binding transcriptional factor and its consensus sequence exists on the HER-2/neu promoter. To examine the role of PEA3 in HER-2/neu expression and cell transformation, we transfected PEA3 into the human breast and ovarian cancer cells that overexpress HER-2/neu and showed that PEA3 dramatically represses HER-2/neu transcription. PEA3 suppresses the oncogenic neu-mediated transformation in mouse fibroblast NIH 3T3 cells. Expression of PEA3 selectively blocks the growth of human cancer cells that overexpress HER-2/neu and inhibits their colony formation. It does not occur in the cancer cells expressing basal level of HER-2/neu. Further studies in the orthotopic ovarian cancer model demonstrated that expression of PEA3 preferentially inhibits growth and tumor development of human cancer cells that overexpress HER-2/neu, the tumor-bearing mice survived significantly longer if treated by injection of the PEA3-liposome complex intraperitoneally. Immunoblotting and immunohistochemical analysis of the tumor tissues indicated that PEA3 mediates the tumor suppression activity through targeting HER-2/neu-p185. Thus, PEA3 is a negative regulator of HER-2/neu gene expression and functions as a tumor suppressor gene in the HER-2/neu-overexpressing human cancer cells.^ The molecular mechanisms of PEA3 mediated transcriptional repression were investigated. PEA3 binds specifically at the PEA3 site on HER-2/neu promoter and this promoter-binding is required for the PEA3 mediated transcriptional repression. Mutation of the PEA3 binding site on HER-2/neu promoter causes decreased transcriptional activity, indicating that the PEA3 binding site is an enhancer-like element in the HER-2/neu-overexpressing cells. We therefore hypothesized that in the HER-2/neu-overexpressing cells, PEA3 competes with a transactivator for binding to the PEA3 site, preventing the putative factor from activating the transcription of HER-2/neu. This hypothesis was supported by the data which demonstrate that PEA3 competes with another nuclear protein for binding to the HER-2/neu promoter in vitro, and expression of a truncated protein which encodes the DNA binding domain of PEA3 is sufficient to repress HER-2/neu transcription in the HER-2/neu-overexpressing human cancer cells. ^

Axl -Gas6 signaling counteracts adenovirus type 5 E1A-mediated cell growth suppression and proapoptotic activity

The adenovirus type 5 E1A (abbreviated E1A) has previously been known as an immortalization oncogene because E1A is required for transforming oncogenes, such as ras and E1B, to transform cells in primary cultures. However, E1A has also been shown to downregulate the overexpression of the Her-2/neu oncogene, resulting in suppression of transformation and tumorigenesis induced by that oncogene. In addition, E1A is able to promote apoptosis induced by anticancer drugs, irradiation, and serum deprivation. Many tyrosine kinases, such as the EGF receptor, Her-2/Neu, Src, and Axl are known to play a role in oncogenic signals in transformed cells. To study the mechanism underlying the E1A-mediated tumor-suppressing function, we exploited a modified tyrosine kinase profile assay (Proc. Natl. Acad. Sci, 93, 5958–5962, 1996) to identify potential tyrosine kinases regulated by E1A. RT-PCR products were synthesized with two degenerate primers derived from the conserved motifs of various tyrosine kinases. A tyrosine kinase downregulated by E1A was identified as Axl by analyzing the Alu I-digested RT-PCR products. We isolated the DNA fragment of interest, and found that E1A negatively regulated the expression of the transforming receptor tyrosine kinase Axl at the transcriptional level. To study whether downregulation of the Axl receptor is involved in E1A-mediated growth suppression, we transfected axl cDNA into E1A-expressing cells (ip1-E1A) to establish cells that overexpressed Axl (ip1-E1A-Axl). The Axl ligand Gas6 triggered a greater mitogenic effect in these ip1-E1A-Axl cells than in the control cells ip1-E1A and protected the Axl-expressing cells from serum deprivation-induced apoptosis. Further study showed that Akt is required for Axl-Gas6 signaling to prevent ip1-E1A-Axl cells from serum deprivation-induced apoptosis. These results indicate that downregulation of the Axl receptor by E1A is involved in E1A-mediated growth suppression and E1A-induced apoptosis, and thereby contributes to E1A's anti-tumor activities. ^

(Table 1) Composition of paraffin hydrocarbons at DSDP Site 56-434

Geochemical investigation of 18 samples of sediments from Site 434 involved determining the content of organic carbon, of bitumoid A (The chloroform A-chl and alcohol-benzene A-alb extracts) and its various fractions, and of individual hydrocarbons as well as the structural group composition of resins. We identified certain samples that differed sharply from the rest by their increased bitumen content and relatively low molecular hydrocarbons and by the fact that their resinous components were more neutral and aliphatic in composition. The distribution of bitumoid and its components seems to reflect migration processes in operation during the early stages of the transformation of organic matter.

En los albores de la celestinesca : Sobre el "Romance nuevamente hecho de Calisto y Melibea" en el pliego suelto de 1513

El Romance nueuamente hecho de Calisto y Melibea, pliego suelto impreso en 1513 (Jacobo Cromberger, Sevilla), un "romance-cuento" (según Menéndez Pidal) de 680 versos octosilábicos, atestigua una pronta transformación genérica: de la prosa dramática de Celestina a un poema narrativo con narrador extradiegético. La trama concisa incluye los típicos motivos narrativos del romancero hispánico (por ejemplo, el protagonista como un cazador) y acentúa el tema del pecado y el castigo (tomado de los paratextos de Celestina), también presente en los primeros pliegos sueltos cantados por ciegos. Existen evidencias de que el texto base ha sido la Comedia, no la Tragicomedia. Este texto temprano debería ser considerado un hito en la historia de la celestinesca

En los albores de la celestinesca : Sobre el "Romance nuevamente hecho de Calisto y Melibea" en el pliego suelto de 1513

El Romance nueuamente hecho de Calisto y Melibea, pliego suelto impreso en 1513 (Jacobo Cromberger, Sevilla), un "romance-cuento" (según Menéndez Pidal) de 680 versos octosilábicos, atestigua una pronta transformación genérica: de la prosa dramática de Celestina a un poema narrativo con narrador extradiegético. La trama concisa incluye los típicos motivos narrativos del romancero hispánico (por ejemplo, el protagonista como un cazador) y acentúa el tema del pecado y el castigo (tomado de los paratextos de Celestina), también presente en los primeros pliegos sueltos cantados por ciegos. Existen evidencias de que el texto base ha sido la Comedia, no la Tragicomedia. Este texto temprano debería ser considerado un hito en la historia de la celestinesca

En los albores de la celestinesca : Sobre el "Romance nuevamente hecho de Calisto y Melibea" en el pliego suelto de 1513

El Romance nueuamente hecho de Calisto y Melibea, pliego suelto impreso en 1513 (Jacobo Cromberger, Sevilla), un "romance-cuento" (según Menéndez Pidal) de 680 versos octosilábicos, atestigua una pronta transformación genérica: de la prosa dramática de Celestina a un poema narrativo con narrador extradiegético. La trama concisa incluye los típicos motivos narrativos del romancero hispánico (por ejemplo, el protagonista como un cazador) y acentúa el tema del pecado y el castigo (tomado de los paratextos de Celestina), también presente en los primeros pliegos sueltos cantados por ciegos. Existen evidencias de que el texto base ha sido la Comedia, no la Tragicomedia. Este texto temprano debería ser considerado un hito en la historia de la celestinesca

Politics of the 1945 Constitution:Democratization and Its Impact on Political Institutions in Indonesia

Introduction : Before 1998, no one could think about the amendment of the 1945 Constitution. The 1945 Constitution was a product of nationalist who had hard fought for independence from the Dutch colonization. This historical background made it the symbol of independence of the Indonesian nation. Thus, it has been considered as forbidden to touch contents of the 1945 Constitution whereas political leaders have legitimized their authoritarian rulership by utilizing a symbolic character of the Constitution. With the largest political turmoil since its independence, that is, a breakdown of authoritarian regime and democratic transformation in 1998-1999, however, a myth of the "sacred and inviolable" constitution has disappeared. A new theme has then aroused: how can the 1945 Constitution be adapted for a new democratic regime in Indonesia? 　　　The Indonesian modern state has applied the 1945 Constitution as the basic law since its independence in 1945, except for around 10 years in the 1950s. In the period of independence struggle, contrary to the constitutional provision that a kind of presidential system is employed, a cabinet responsible for the Central National Committee was installed. Politics under this institution was in practice a parliamentary system of government. After the Dutch transferred sovereignty to Indonesia in 1949, West European constitutionalism and party politics under a parliamentary system was fully adopted with the introduction of two new constitutions: the 1949 Constitution of Federal Republic of Indonesia and the 1950 Provisional Constitution of Republic of Indonesia. Since a return from the 1950 Constitution to the 1945 Constitution was decided with the Presidential Decree in 1959, the 1945 Constitution had supported two authoritarian regimes of Soekarno's "Guided Democracy" and Soeharto's "New Order" as a legal base. When the 32-year Soeharto's government fell down and democratization started in 1998, the 1945 Constitution was not replaced with a new one, as seen in many other democratizing countries, but successively reformed to adapt itself to a new democratic regime. In the result of four constitutional amendments in 1999-2002, political institutions in Indonesia are experiencing a transformation from an authoritative structure, in which the executive branch monopolized power along with incompetent legislative and judicial branches, to a modern democratic structure, in which the legislative branch can maintain predominance over the executive. However, as observed that President Abdurrahman Wahid, the first president ever elected democratically in Indonesian history, was impeached after one and a half years in office, democratic politics under a new political institution has never been stable. 　　　Under the 1945 Constitution, how did authoritarian regimes maintain stability? Why can a democratic regime not achieve its stability? What did the two constitutional amendments in the process of democratization change? In the first place, how did the political institutions stipulated by the 1945 Constitution come out? Through answering the above questions, this chapter intends to survey the historical continuity and change of political institutions in Indonesia along with the 1945 Constitutions and to analyze impact of regime transformation on political institutions. First, we examine political institutions stipulated by the original 1945 Constitution as well as historical and philosophical origins of the constitution. Second, we search constitutional foundations in the 1945 Constitution that made it possible for Soekarno and Soeharto to establish and maintain authoritarian regimes. Third, we examine contents of constitutional amendments in the process of democratization since 1998. Fourth, we analyze new political dynamics caused by constitutional changes, looking at the impeachment process of President Abdurrahman Wahid. Finally, we consider tasks faced by Indonesia that seeks to establish a stable democracy.

Reduction of truncation errors in planar, cylindrical and partial spherical near-field antenna measurements

A method to reduce truncation errors in near-field antenna measurements is presented. The method is based on the Gerchberg-Papoulis iterative algorithm used to extrapolate band-limited functions and it is able to extend the valid region of the calculated far-field pattern up to the whole forward hemisphere. The extension of the valid region is achieved by the iterative application of a transformation between two different domains. After each transformation, a filtering process that is based on known information at each domain is applied. The first domain is the spectral domain in which the plane wave spectrum (PWS) is reliable only within a known region. The second domain is the field distribution over the antenna under test (AUT) plane in which the desired field is assumed to be concentrated on the antenna aperture. The method can be applied to any scanning geometry, but in this paper, only the planar, cylindrical, and partial spherical near-field measurements are considered. Several simulation and measurement examples are presented to verify the effectiveness of the method.

A flexible (C)LP-based approach to the analysis of object-oriented programs

Static analyses of object-oriented programs usually rely on intermediate representations that respect the original semantics while having a more uniform and basic syntax. Most of the work involving object-oriented languages and abstract interpretation usually omits the description of that language or just refers to the Control Flow Graph(CFG) it represents. However, this lack of formalization on one hand results in an absence of assurances regarding the correctness of the transformation and on the other it typically strongly couples the analysis to the source language. In this work we present a framework for analysis of object-oriented languages in which in a first phase we transform the input program into a representation based on Horn clauses. This allows on one hand proving the transformation correct attending to a simple condition and on the other being able to apply an existing analyzer for (constraint) logic programming to automatically derive a safe approximation of the semantics of the original program. The approach is flexible in the sense that the first phase decouples the analyzer from most languagedependent features, and correct because the set of Horn clauses returned by the transformation phase safely approximates the standard semantics of the input program. The resulting analysis is also reasonably scalable due to the use of mature, modular (C)LP-based analyzers. The overall approach allows us to report results for medium-sized programs.

Development of novel melt-processable biopolymer nanocomposites based on poly(L-lactic acid) and WS2 inorganic nanotubes.

The use of tungsten disulphide inorganic nanotubes (INT-WS2) offers the opportunity to produce novel and advanced biopolymer-based nanocomposite materials with excellent nanoparticle dispersion without the need for modifiers or surfactants via conventional melt blending. The study of the non-isothermal melt-crystallization kinetics provides a clear picture of the transformation of poly(L-lactic acid) (PLLA) molecules from the non-ordered to the ordered state. The overall crystallization rate, final crystallinity and subsequent melting behaviour of PLLA were controlled by both the incorporation of INT-WS2 and the variation of the cooling rate. In particular, it was shown that INT-WS2 exhibits much more prominent nucleation activity on the crystallization of PLLA than other specific nucleating agents or nano-sized fillers. These features may be advantageous for the enhancement of mechanical properties and process-ability of PLLA-based materials. PLLA/INT-WS2 nanocomposites can be employed as low cost biodegradable materials for many eco-friendly and medical applications, and the exceptional crystallization behaviour observed opens new perspectives for scale-up and broader applications.

Analysis of the suitability of existing medical ontologies for building a scalable semantic interoperability solution supporting multi-site collaboration in oncology

Semantic interoperability is essential to facilitate efficient collaboration in heterogeneous multi-site healthcare environments. The deployment of a semantic interoperability solution has the potential to enable a wide range of informatics supported applications in clinical care and research both within as ingle healthcare organization and in a network of organizations. At the same time, building and deploying a semantic interoperability solution may require significant effort to carryout data transformation and to harmonize the semantics of the information in the different systems. Our approach to semantic interoperability leverages existing healthcare standards and ontologies, focusing first on specific clinical domains and key applications, and gradually expanding the solution when needed. An important objective of this work is to create a semantic link between clinical research and care environments to enable applications such as streamlining the execution of multi-centric clinical trials, including the identification of eligible patients for the trials. This paper presents an analysis of the suitability of several widely-used medical ontologies in the clinical domain: SNOMED-CT, LOINC, MedDRA, to capture the semantics of the clinical trial eligibility criteria, of the clinical trial data (e.g., Clinical Report Forms), and of the corresponding patient record data that would enable the automatic identification of eligible patients. Next to the coverage provided by the ontologies we evaluate and compare the sizes of the sets of relevant concepts and their relative frequency to estimate the cost of data transformation, of building the necessary semantic mappings, and of extending the solution to new domains. This analysis shows that our approach is both feasible and scalable.