Pre-established Models Research Articles

Abstract B124: Preclinical development of a novel therapeutic antibody to treat pancreas and colorectal cancers

Abstract NPC-1C is a chimeric monoclonal antibody being developed as a novel biological treatment for pancreatic and colorectal cancers. This antibody was selected from a panel of hybridomas generated from mice immunized with semi-purified membrane-associated proteins derived from biologically screened, pooled human allogeneic colon cancer tissues. NPC-1C appears to recognize an aberrantly expressed form of MUC5AC expressed specifically by human colon and pancreatic tumor tissues and cell lines. NPC-1C does not cross-react with normal human tissues (and with MUC5AC from other type of cancers), however, except for occasional, weak binding to certain GI tract tissues, which may indicate a pre-malignant state. In vitro, the NPC-1C antibody exhibits specific ADCC activity against human colon and pancreatic tumor cells, but not against control tumor cell lines. In vivo, the anti-tumor efficacy of NPC-1C was tested using preestablished subcutaneous human pancreatic tumor xenograft models. The data showed significant, and reproducible, anti-tumor action, including some complete tumor regressions. The clinical application for this antibody was bolstered by several examples of human tumor tissues were stained with biotin-conjugated NPC-1C which show a strong correlation of NPC-1C staining against pancreatic and colon tumors, with approximately 45% of tumors staining strongly positive. The staining pattern was typical of mucin expression, but also showed cytoplasmic and cell membrane staining. The pre-clinical toxicity profile of NPC-1C in normal BALB/c mice demonstrated little, if any, toxicity following single or multiple intravenous injections of 10 mg/kg, 50 mg/kg, or 100 mg/kg of clinical-grade NPC-1C antibody. Toxicity parameters measured include body weight, food consumption, complete blood analysis, serum chemistries, gross pathology, and microscopic histopathology. The bio-distribution of radio-labeled NPC-1C in mice with pre-established subcutaneous human tumors revealed specific accumulation of NPC-1C at the tumor site, with little or no binding or accumulation in several major organ systems. Finally, we studied the cytokine and antibody responses to NPC-1C in the pre-clinical mouse model. Although anti-NPC-1C antibodies were detected (as expected) in a time-dependent fashion, we did not detect changes in Type I (IL-2 or g-IFN) and Type II (IL-4 or IL-5) cytokines in response to up to 100 mg/kg of NPC-1C either 3 days or 14 days after intravenous administration. The pre-clinical development of NPC-1C indicates that it is safe and efficacious, and suggest that it should be well-tolerated and may have clinical activity in patients whose tumor expresses the altered MUC5AC epitope. The FDA has approved the Investigational New Drug (IND) application to initiate a Phase I clinical trial with NPC-1C for patients with advanced pancreatic and colorectal cancer. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B124.

Non-invasive metabolomic profiling of day 3 and 5 embryo culture media using near infrared spectroscopy: predictions using pre-established models

OBJECTIVE: ART pregnancy rates are high in the U.S., yet multiple embryo transfer continues as a treatment modality despite concerns regarding the incidence of multi-fetal pregnancies. Single embryo transfer (SET) is the only effective way to minimize the risks of multiple gestations. The objective of this study was to use a non-invasive metabolomic profiling technique based on Near Infra Red (NIR) spectroscopy to predict the implantation potential of Day 3 (D3) and 5 (D5) embryos that had been singly transferred.DESIGN: Analysis of embryo culture media from D3 and D5 embryos of SET cohorts in a private IVF center.MATERIALS AND METHODS: D3 and D5 SETs were performed at the Reproductive Science Center (RSC), Lexington, MA, USA (N=122 for D3 and N=25 for D5). Embryos were selected for SET using routine morphologic criteria and grading. Embryos were cultured individually in 30 μl under mineral oil to D3 in either Global or Sage Cleavage Medium and in Global Medium to D5. Post-SET, the medium in which the embryo had developed and a matching control medium were immediately frozen and sent to Molecular Biometrics, Inc. for analysis. Ongoing pregnancy was defined by the observation of fetal cardiac activity (FCA). A pre-established Molecular Biometrics D3 and D5 algorithm for a “Viability Index” predictive of pregnancy outcome was blindly assigned and applied to the embryo culture media samples collected at RSC.RESULTS: When the D3 embryo culutre media were blindly assessed, a significant difference (p=0.013) in the mean (±SD) “Viability Index” scores between the FCA- positive (0.51±0.23) and negative (0.39±0.31) samples was identified. A signficant (p=0.036) difference was also found for the smaller set of D5 SET media: FCA- positive (0.52±0.52) and negative (0.15±0.46). In general, in both data sets, as the Viability Index scores increased, their associated FCA-positive embryo implantations also increased.CONCLUSIONS: This study has shown that a pre-established D3 and 5 algorithm for analysis of spent embryo culture medium by NIR spectrophotometric analysis can contribute to the identification of embryos with a metabolomic profile, or “Viability Index” score, that may be predictive of implantation potential. Metabolomic profiling could provide a useful technology for assisting clinics in the US to move towards SET. OBJECTIVE: ART pregnancy rates are high in the U.S., yet multiple embryo transfer continues as a treatment modality despite concerns regarding the incidence of multi-fetal pregnancies. Single embryo transfer (SET) is the only effective way to minimize the risks of multiple gestations. The objective of this study was to use a non-invasive metabolomic profiling technique based on Near Infra Red (NIR) spectroscopy to predict the implantation potential of Day 3 (D3) and 5 (D5) embryos that had been singly transferred. DESIGN: Analysis of embryo culture media from D3 and D5 embryos of SET cohorts in a private IVF center. MATERIALS AND METHODS: D3 and D5 SETs were performed at the Reproductive Science Center (RSC), Lexington, MA, USA (N=122 for D3 and N=25 for D5). Embryos were selected for SET using routine morphologic criteria and grading. Embryos were cultured individually in 30 μl under mineral oil to D3 in either Global or Sage Cleavage Medium and in Global Medium to D5. Post-SET, the medium in which the embryo had developed and a matching control medium were immediately frozen and sent to Molecular Biometrics, Inc. for analysis. Ongoing pregnancy was defined by the observation of fetal cardiac activity (FCA). A pre-established Molecular Biometrics D3 and D5 algorithm for a “Viability Index” predictive of pregnancy outcome was blindly assigned and applied to the embryo culture media samples collected at RSC. RESULTS: When the D3 embryo culutre media were blindly assessed, a significant difference (p=0.013) in the mean (±SD) “Viability Index” scores between the FCA- positive (0.51±0.23) and negative (0.39±0.31) samples was identified. A signficant (p=0.036) difference was also found for the smaller set of D5 SET media: FCA- positive (0.52±0.52) and negative (0.15±0.46). In general, in both data sets, as the Viability Index scores increased, their associated FCA-positive embryo implantations also increased. CONCLUSIONS: This study has shown that a pre-established D3 and 5 algorithm for analysis of spent embryo culture medium by NIR spectrophotometric analysis can contribute to the identification of embryos with a metabolomic profile, or “Viability Index” score, that may be predictive of implantation potential. Metabolomic profiling could provide a useful technology for assisting clinics in the US to move towards SET.

Semiautomated Building Extraction Based on CSG Model-Image Fitting

mostly implemented in a semi-automatic manner, solving the Building extraction based on pre-established models has been model-image fitting problem based on some high-level inforrecognized as a promising idea for acquiring 3D data for build- mation given by the operator. The spatial data of a building ings from aerial images. This paper proposes a novel building object are determined, when model-image fitting is achieved. extraction method developed from the concept of fitting CSG In contrast to the traditional point-by-point mapping proce(Constructive Solid Geometry) primitives to aerial images. To dure, model-based building extraction features object-based be practicable, this method adopts a semiautomatic proce- data acquisition. Although the idea and benefits of modeldure, carrying out high-level tasks (building detection, model based building extraction have been acknowledged, the workselection, and attribution) interactively by the operator and ing principle is not well established. Therefore, the focus of performing optimal model-image fitting automatically with a this study is to establish a practical theory for model-based least-squares fitting algorithm. Buildings, represented by CSG building extraction. models, can be reconstructed part by part after fitting each Building modeling and model-image fitting are the key parameterized CSG primitive to the edge pixels of aerial issues in model-based building extraction. The issue on buildimages. Reconstructed building parts can then be combined ing modeling is how to establish a set of representative and using CSG Boolean set operators. Consequently, a building is complete building models. This paper reviews some building represented by a CSG tree in which each node links two model schemes known in the field of digital photogrammetry branches of combined parts. This paper demonstrates ten and discusses how CSG modeling is employed in the proposed examples of building extraction from aerial photos taken at a method. The issue in model-image fitting is how to develop a scale of 1:5,000 and scanned at a pixel size of 25 m. All of computer algorithm that is able to determine the pose and the tests were performed in the prototypal system implemented shape parameters of an object model such that the edge lines of in a CAD-based environment cooperated with a number of the wire frame, as projected into the images, are optimally specially designed programs. The process time for each prim- coincident with the corresponding edge pixels. It is assumed itive is about 20 seconds and the successful rate of model- that the image orientations are known and that the pose and image fitting was about 90 percent. Evaluated with some check shape parameters are approximately determined through an points, the fitting accuracy was about 0.3 m horizontally and interactive manual process. To deal with this problem, this 1m vertically. The test results are encouraging and promote paper proposes a tailored least-squares model-image fitting the theory of model-based building extraction. algorithm as the key component of the building extraction framework.

Terapia ocupacional social

The aim of this paper is to discuss the unfolding of a new research area - seen both as a field for theoretical reflection and as a praxis of intervention: the so called 'social occupational therapy', which has been defined to be the body of knowledge related to processes of caring and dealing with people lacking an adequate social support net. To that purpose, we address ourselves to the following tasks: the first is to understand which occupational therapy has emerged outside the main organizing framework 'health-disease'; the second one is to disclose the intertwining relations between occupational therapy and the society and culture within which it has been effectively developed. We consider that it is important to outline methodological principles that allow us to think out our practices, beyond the empirical moment; but we also believe that this has to be done without narrowing our reflections to the limits of reducing theories or pre-established models, a restriction that would make it impossible to fully understand the movements of the real world, life and history within their own context. In order to do so, we review the recent history of occupational therapy and investigate: the emergence of the 'social question', concerning reflection and practices in occupational therapy in São Paulo; the 'social' as a context of intervention of the occupational therapist; the processes of desinstitutionalisation; the importance of territorial actions in occupational therapy and, finally, the concepts that allow us to define the attention to social groups submitted to situations of rupture of their supporting social nets as a practice of occupational therapy.

Dismantling Romantic Utopias: María Beneyto's Poetry Between Tradition and Protest

Despite the fact that Vicente Aleixandre considered her one of the best young authors of the generation of social poets of the 1950s, María Beneyto's writings have been disregarded by critics. While sharing the social concerns of the other poets of her generation, Beneyto's poetry also reveals the dilemma of the woman author facing a cultural tradition that espouses pre-established models for her conduct and identity patterned mostly in accordance with tenets of Romanticism. Beneyto resorts to those models as projections of herself as she seeks to articulate her own identity as woman and author. The objective of this essay is to explore Beneyto's reflection on her own identity as woman and poet and, through that process, on the nature of poetic language. By adopting the identity of Eve as the embodiment of instinctual and primitive life that culture has suppressed, or by addressing the role of the mother or angel of the hearth, or the identity of Ophelia, George Sand, or Madame Bovary, Beneyto's poetic speaker hopes to make audible their silenced voices and to contest the rigidity that cultural convention imposes on those roles. Beneyto's poetry destabilizes the essentialism of those models and comes to an understanding of female identity and writing as a constant process of redefinition based on the individual woman's exchanges with the surrounding context.

"Nothing Was Lost in the Masquerade": The Protean Performance of Genre and Identity in Charles Johnson's Oxherding Tale

As many times as we reopen slavery's closure, we are hurtled rapidly forward into dizzying motions of symbolic enterprise, and it becomes increasingly clear that cultural synthesis we call slavery was never homogeneous in its practices and conception, nor unitary in faces it has yielded. But to behave as if it were so matches precisely telos of African persons in United States.... The collective and individual reinvention of discourse of slavery is, therefore, nothing other than an attempt to restore to spatio-temporal object its eminent historicity, to evoke person/persona in place of shady ideal. (Spillers, Changing Letter 29) In his novel Oxherding Tale (1982), Charles Johnson reopens slavery's closure through his reclamation of nineteenth-century slave narrative. In so doing, he undermines static formulations of literature, history, and identity: Viewing each account as potentially mutable rendering of and being, he limns their transformative through performative poetics. Just as Spillers posits slavery's closure as point of departure for recovery of that institution's complex historicity, Johnson deploys seemingly fixed categories of identity and genre in order to overturn deterministic models of being. Specifically, his enslaved, biracial protagonist Andrew Hawkins can only achieve emancipation by comprehending his own subjectivity as multiple, as heterogeneously constructed out of interstices between house and field, and white and black. In keeping with this new understanding, Andrew in his role as narrator must also transcend perspective and confines of traditional autobiography in order to enact first-person universal. By extension, Johnson forces his readers to confront limitations of conventional, realist reading method (as he calls it, a heavily conditioned seeing), proposing as an alterna- tive more liberated mode of readership (Being 5). Thus, Johnson seizes discursive aspect of slavery's displaced person(s)/persona(s): Refusing to fix subject, he instead conceives of personhood as effect of reiterative and citational practice, as palimpsest of performances. In both Johnson's philosophical fictions and his philosophy of fiction, he interrogates questions of subjectivity in relation to language and literary form. As he states in his phenomenological treatise on African-American fiction Being and Race (1988), he reserves his greatest respect for the protean writer, performer . . . who slides from genre to genre, style to style, leaving his or her distinctive signature on each form lovingly transfigured and pushed toward new possibilities (53). Here, Johnson challenges orthodoxy that impels black writers to adhere to realism as primary literary mode. Rejecting what he deems calcified vision, Johnson cautions writer against adopting preestablished models . . . for our experience, or for any experience (7). Instead, he calls for African-American writer to grapple with perceptual flux of that characterizes black world - and all worlds - to originate new meaning (15). In Johnson's view, then, good fiction should not only transgress generic boundaries, but it should also strategically stage these traversals in service of liberty for benefit of reader and writer. Using his principles to guide my own critique, I read Oxherding Tale as text which performs myriad versions of genre and identity in order to attain ontological and narrative freedom. As post-modern subversion of classical American slave narrative with resonances of an Eastern parable, novel exemplifies Johnson's own protean dictate[middle dot] By reiterating and mimicking these disparate literary traditions, Johnson invents his characters through complex citational process which allows him to critique notions of authenticity and essentialism and to negotiate new constructions of personhood (Parker and Sedgwick 2). …

The Consumption of Dependency Theory in the United States

If an observer from outer space had landed his UFO at any meeting of Latin Americanists during the last few years, he would have had to agree with the structural anthropologists. He would have said that at these meetings, versions of the same myth are constantly repeated: dependency and development, exploitation and wealth, backwardness and sophisticated technology, unemployment and extreme concentration of income. Somewhat wearily, our creature from space would have commented: “The brains of these beings appear to limit their images and thoughts to binary opposites.” Returning to the debate on the meaning of analyses of dependency gives one the sensation of entering a discussion in which imagination is bound by preestablished models. Nevertheless, as though I were one of the “founding fathers” of dependency, I endorse the ceremonial consumption of the theme. How to escape from this uncomfortable position?