Investigating transmembrane-lipid interactions of EphA2 and pH responsive peptides

Single-pass membrane receptor signaling plays vital roles in human development and maintaining homeostasis. These membrane receptors can also have causative functions in several diseases including cancer. Much is known about the structure and signaling outcomes of these receptors but the mechanistic details of how they pass an extracellular signal across the membrane and into cytoplasm via the transmembrane (TM) domain is unclear. It is further unknown how or if interactions with membrane lipids facilitate and/or regulate these events. Here we use the TYPE7 peptide to target the TM region of a receptor tyrosine kinase, EphA2. EphA2 engages in both tumorigenic (ligand-independent) and anti-tumorigenic (ligand-dependent) signaling making it an attractive drug target. From TYPE7 we learned that the activity of EphA2 could be modulated by interactions with a TM peptide. Findings from TYPE7 (Chapter II), lead to hypotheses about the signaling states of EphA2 and interactions with anionic lipids. We next demonstrated (Chapter III) that there is a TM conformation-specific coupling of juxtamembrane residues of EphA2 with PIP2 [phosphatidylinositol 4,5-bisphosphate]. Our data suggests that PIP2 promotes dimerization of EphA2 in the ligand-independent state, potentially regulating tumorigenic signaling. These findings add to the knowledge of the molecular events of EphA2 signal transduction which is vital to designing effective therapeutics. Finally, we investigated the effects that TM peptides can have on their lipid environments. We developed (Chapter IV) a fluorescence recovery after photobleaching (FRAP) protocol and an automated data analysis pipeline using programs written in Python and Mathematica languages for the determination of lipid diffusion coefficients. We used the pH responsive peptide (pHLIP) as a model TM domain and FRAP in supported lipid bilayers to investigate the effect of pHLIP on the rate of lipid diffusion

Spin chain from membrane and the Neumann-Rosochatius integrable system

We find membrane configurations in AdS_4 x S^7, which correspond to the continuous limit of the SU(2) integrable spin chain, considered as a limit of the SU(3) spin chain, arising in N=4 SYM in four dimensions, dual to strings in AdS_5 x S^5. We also discuss the relationship with the Neumann-Rosochatius integrable system at the level of Lagrangians, comparing the string and membrane cases.Comment: LaTeX, 16 pages, no figures; v2: 17 pages, title changed, explanations and references added; v3: more explanations added; v4: typos fixed, to appear in Phys. Rev.

Open Semiclassical Strings and Long Defect Operators in AdS/dCFT Correspondence

We consider defect composite operators in a defect superconformal field theory obtained by inserting an AdS_4 x S^2-brane in the AdS_5 x S^5 background. The one-loop dilatation operator for the scalar sector is represented by an integrable open spin chain. We give a description to construct coherent states for the open spin chain. Then, by evaluating the expectation value of the Hamiltonian with the coherent states in a long operator limit, a Landau-Lifshitz type of sigma model action is obtained. This action is also derived from the string action and hence we find a complete agreement in both SYM and string sides. We see that an SO(3)_H pulsating string solution is included in the action and its energy completely agrees with the result calculated in a different method. In addition, we argue that our procedure would be applicable to other AdS-brane cases.Comment: 22 pages, 1 figure, LaTeX, minor corrections and references added. v3) some new results added. shortened and accepted version in PR

Semiclassical Strings in Electric and Magnetic Fields Deformed AdS5×S5AdS_5 \times S^5 Spacetimes

We first apply the transformation of mixing azimuthal and internal coordinate or mixing time and internal coordinate to the 11D M-theory with a stack N M2-branes to find the spacetime of a stack of N D2-branes with magnetic or electric flux in 10 D IIA string theory, after the Kaluza-Klein reduction. We then perform the T duality to the spacetime to find the background of a stack of N D3-branes with magnetic or electric flux. In the near-horizon limit the background becomes the magnetic or electric field deformed $AdS_5 \times S^5$. We adopt an ansatz to find the classical string solution which is rotating in the deformed $S^5$ with three angular momenta in the three rotation planes. The relations between the classical string energy and its angular momenta are found and results show that the external magnetic and electric fluxes will increase the string energy. Therefore, from the AdS/CFT point of view, the corrections of the anomalous dimensions of operators in the dual SYM theory will be positive. We also investigate the small fluctuations in these solutions and discuss the effects of magnetic and electric fields on the stability of these classical rotating string solutions. Finally, we find the possible solutions of string pulsating on the deformed spacetimes and show that the corrections to the anomalous dimensions of operators in the dual SYM theory are non-negative.Comment: Latex 18 pages, correct sec. 3.

A Hybrid Medium Voltage Multilevel Converter with Parallel Voltage-Source Active Filter

In consequence of high semiconductor losses, grid-connected medium voltage power converters are typically operated at switching frequencies of several hundred Hertz per switch position. Therefore, conventional converter systems require bulky and expensive LCL-filters in order to meet the harmonic limits given by the grid code. It is only possible to reduce the LCL-filter costs by semiconductor current derating and operation at increased switching frequencies, leading to a reduced utilization and efficiency of the converter system. To overcome these disadvantages of conventional converter systems, the presented hybrid converter uses a parallel voltage-source active output filter and thus allows a significant reduction of the passive component demand. An excellent harmonic performance is achieved for the operation with small passive filter components, revealing the potential for increasing the power density and efficiency of high power medium voltage converters. As a result, significant reductions of the filter losses and passive components as well as an increased utilization are achieved compared to a reference LCL-filter based converter system

Addressing Disciplinary Literacy: An Examination of Teachers’ Instruction in First Grade

Disciplinary literacy instruction during kindergarten through second grade enables students to begin developing facility with consuming, producing, and learning from texts in academic disciplines across their school careers and for full civic participation. Extant intervention studies and descriptions of practice in the primary grades offer understanding of disciplinary literacy instruction when it is enacted with researchers’ help and/or by teachers with expertise in disciplinary literacy. To address disciplinary literacy in the primary grades, insight into what primary teachers focus on and how they support students’ disciplinary literacy learning during their naturally-occurring instruction is needed. This exploratory collective case study examined the disciplinary literacy learning opportunities available in first-grade teachers’ instruction. Participants included four teachers in four elementary schools situated in a large city in the Midwest. Audio records and field notes were collected over a period of five months during teachers’ literacy instruction. Open coding, progressive refinement of codes, and categorical analyses revealed limited instructional emphasis on disciplinary literacy. When learning opportunities were observed, teachers’ foci and support centered on the social foundations of disciplinary literacy and included sharing of information and student practice. Also, problematic disciplinary literacy learning opportunities were noted. This study underscores the urgent need for additional attention to disciplinary literacy as it is situated within the primary grades, with particular import for how first-grade teachers enact disciplinary literacy instruction

Preservice Teacher Sense-Making as They Learn to Teach Reading as Seen Through Computer-Mediated Discourse

Abstract This collective case study used methods of discourse analysis to consider what computer-mediated collaboration might reveal about preservice teachers’ sense-making in a field-based practicum as they learn to teach reading to children identified as struggling readers. Researchers agree that field-based experiences coupled with time for reflection benefit preservice teachers as they learn to teach reading. However, research is not as clear about which features of practicum experiences lead to preservice teacher learning, which may contribute to preservice teacher misconceptions, and how learning about reading instruction might be rendered more visible to researchers. Grounded in sociocultural perspectives, analysis focused on language as a mediating tool for the construction of knowledge. Data collection spanned three semesters in a literacy assessment and intervention practicum. Preservice teachers constructed understandings of readers and reading instruction through reflecting, planning, and articulating their decision-making processes with one another in the online discussion board. Findings indicated that analysis of preservice teachers’ computer-mediated discussions provided a window into their sense-making processes. While some preservice teachers’ discourse demonstrated marked growth, other preservice teachers’ limited use of precise language related to reading assessment and intervention frequently inhibited their developing understandings and instructional decisions. As well, some of the decisions instructors made likely contributed to several PST misconceptions. We conclude with implications for computer-supported collaborative environments in teacher education as a means to make preservice teacher learning more visible and accessible as a tool for teaching and learning

Science-Literacy Integration: Equity and Learning in First-Grade, Urban Instructional Contexts

Previous research demonstrates that integration of science and literacy instruction in primary grades has positive outcomes for students’ science and literacy development. However, variations in how science and literacy are enacted suggest integration may not be sufficient to meet the literacy and science needs of all students in an equitable manner. The purpose of this study was to examine two first-grade teachers’ science integration during literacy instruction in one high- and one low-income school context within one urban district. Analysis of field notes, transcripts of lessons, and interviews revealed that expectations to integrate science during time set aside for literacy instruction without consideration of contextual factors perpetuated and concealed ongoing inequities in science education for students from the lowest income school. Further, this study adds to evidence from prior studies demonstrating that reading of science-related texts alone, as a substitute for instruction in science as a discipline, does not provide students with the resources needed to learn to think, talk, and act as scientists. Findings from this study require researchers and policy-makers to address the context-specific factors that shape instructional contexts in ways that limit or expand the potential of integrated science–literacy instruction in urban schools