Imaging Molecular Structure of Channels and Receptors with an Atomic Force Microscope

Biological membranes contain specialized protein macromolecules such as channels, pumps and receptors. Physiologically, membranes and their constituent macromolecules are the interface surfaces toward which most of the regulatory biochemical and other signals are directed. Yet very little is known about these surfaces. The structure of biological membranes has been analyzed primarily using imaging techniques that are limited in their resolution of surface topology. An atomic force microscope (AFM) developed by Binnig, Quate and Gerber, can image molecular structures on specimen surfaces with subnanometer resolution, under diverse environmental conditions. Also, AFM can manipulate surfaces with molecular precision: it can nanodissect, translocate, and reorganize molecules on surfaces. The surface topology has been imaged for several hydrated channels, pumps and receptors which were a) present in isolated native membranes, b) reconstituted in artificial membrane or, c) expressed in an appropriate expression system. These images, at molecular resolution, reveal exciting new findings about their architecture. AFM induced force dissection reveals surfaces which are commonly inaccessible. In whole cell studies, in addition to the molecular structure of membrane receptors and channels, correlative electrical and biochemical activities have been examined. Such study suggests a single cell experiment where the structure-function correlation of many cloned channels and receptors can be understood

The influence of consumers' goals on selective attention to product features.

Although attention is a key construct in models of marketing communications and consumer choice, its selective nature has rarely been examined in the time-pressured conditions that consumers face everyday. We investigate how consumers' goals influence selective attention to product features under such conditions. Specifically, we focus on the role of goal salience, that is, the readiness with which particular goals (e.g., personalized customer service) are brought to mind by consumers in relation to a given product category (e.g., banks). Study1 demonstrated that when product feature information was presented rapidly, individuals for whom the goal of personalized customer service had high chronic or habitual salience displayed selective attention in terms of their elevated recall of a target feature (a bank's 'friendly employees'). Also, as expected, individual differences in chronic goal salience affected judgments of the target product. Study2 showed that when subjects were additionally informed about a specific product usage situation (e.g., being new in town or experiencing difficulty in balancing a checkbook), selective attention was no longer affected by individuals' chronic tendencies. Instead, both feature recall and judgments were influenced by the relevance of the target feature to the goals made salient by the situational context. Discussion emphasizes the theoretical and managerial implications of the findings regarding the role of goal salience in selective attention to product features.Product;

Benefit salience and consumers' selective attention to product features.

Although attention is a key construct in models of marketing communication and consumer choice, its selective nature has rarely been examined in common time-pressured conditions. We focus on the role of benefit salience, that is, the readiness with which particular benefits are brought to mind by consumers in relation to a given product category. Study I demonstrated that when product feature information was presented rapidly, individuals for whom the benefit of personalised customer service had high habitual salience displayed selective attention as evidenced by elevated recall and recognition of a target feature (a bank's ''friendly employees''). Also, as expected, individual differences in habitual benefit salience affected judgements of the target product. Study 2 showed that when subjects were additionally informed about a specific product usage situation, selective attention was primarily influenced by the relevance of the target feature to benefits made salient by the usage situation; individual differences played a less important role. Discussion emphasises theoretical aspects of the findings as well as managerial implications with respect to person-situation approaches to benefit segmentation. (C) 1997 Elsevier Science B.V.attention; benefit segmentation; individual construct accessibility; usage context; involvement; segmentation; substitution; experiences; memory; recall; choice; link;

Upgrading the capstone projects: The engineering clinic model

Capstone engineering design projects are ideal for broad application of engineering concepts on open-ended research and design problems. These projects allow students to reinforce their skills and extend their expertise into specialized areas of interest. Often, the capstone projects serve as both test grounds and launch pads for students’ engineering careers. Within the engineering curriculum, these projects typically span the final year of an engineering program and entail a single project within a single disciplinary area. While their significance to the educational experience is unequivocal, the benefits of a capstone project can be expanded to further reflect real-world experiences. Over the span of their careers, professional engineers work on a number of projects and assume a variety of roles within a team of engineers with a range of expertise. How do we model that experience for our students within engineering education? Rowan University’s Henry M. Rowan College of Engineering adopted the Engineering Clinic Model (ECM) to replace capstone projects. With ECM students choose to work across traditional disciplinary boundaries on multiple projects over their junior and senior years. The Junior and Senior Engineering Clinics allow students to work on potentially four distinct projects with both juniors and seniors from any engineering discipline supervised by a faculty. The student teams focus on tangible objectives and present their outcomes for each term before moving to another team. The ECM has demonstrated tremendous resilience against enrollment growth and continues to be the most notable aspect of Rowan Engineering. Its resilience can be attributed to an automated process that prioritizes student preferences and faculty interests. The process begins with faculty from every engineering discipline pitching their projects at the start of the term. Students subsequently rank their preferences for those projects. A custom-developed Clinic Match algorithm assigns students to their projects based on a set criteria. The greatest benefit of this approach has been for the students to build desired competencies in a wide range of fields, regardless of the discipline. For the Spring 2019 semester, over 150 distinct projects, representing 5 engineering disciplines, were pitched to over 500 junior and senior engineering students. Students worked in teams typically ranging from 3-8 members on projects; often funded by the government and industry. This paper highlights the key features of engineering clinics within junior and senior years and supports the outcomes with quantitative trends gathered over the past 10 semesters. The Junior and Senior Engineering Clinics offer a powerful alternative for leveraging the capstone design project to impart a broad skill set among engineering graduates

The 43-kD polypeptide of heart gap junctions: immunolocalization, topology, and functional domains

Analysis by SDS-PAGE of gap junction fractions isolated from heart suggests that the junctions are comprised of a protein with an Mr 43,000. Antibodies against the electroeluted protein and a peptide representing the 20 amino terminal residues bind specifically on immunoblots to the 43-kD protein and to the major products arising from proteolysis during isolation. By immunocytochemistry, the protein is found in ventricle and atrium in patterns consistent with the known distribution of gap junctions. Both antibodies bind exclusively to gap junctions in fractions from heart examined by EM after gold labeling. Since only domains of the protein exposed at the cytoplasmic surface should be accessible to antibody, we conclude that the 43-kD protein is assembled in gap junctions with the amino terminus of the molecule exposed on the cytoplasmic side of the bilayer, that is, on the same side as the carboxy terminus as determined previously. By combining proteolysis experiments with data from immunoblotting, we can identify a third cytoplasmic region, a loop of some 4 kD between membrane protected domains. This loop carries an antibody binding site. The protein, if transmembrane, is therefore likely to cross the membrane four times. We have used the same antisera to ascertain if the 43-kD protein is involved in cell-cell communication. The antiserum against the amino terminus blocked dye coupling in 90% of cell pairs tested; the antiserum recognizing epitopes in the cytoplasmic loop and cytoplasmic tail blocked coupling in 75% of cell pairs tested. Preimmune serum and control antibodies (one against MIP and another binding to a cardiac G protein) had no or little effect on dye transfer. Our experimental evidence thus indicates that, in spite of the differences in amino acid sequence, the gap junction proteins in heart and liver share a general organizational plan and that there may be several domains (including the amino terminus) of the molecule that are involved in the control of junctional permeability

Development of a Composite Tailoring Technique for Airplane Wing

Development of a new composite beam modeling technique to represent the principal load-carrying member in the wing is reported along with the development of a formal design optimization procedure to investigate the effect of composite tailoring on aeroelastic stability and structural characteristics of airplane wings. The developed procedure is used to perform design optimization studies on realistic airplane configurations to investigate the various aeroelastic/structural/dynamic design issues

The Appropriateness of Different Modes of Strategy from a Product-Market Perspective

Strategy-making is an important yet complex task. The present research examines the issue of strategy mode, that is, the manner or style in which strategy is determined in an organization. Prior researchers have proposed various typologies for strategy modes. However, research into which strategy modes are appropriate to what kinds of firm situations and contexts has been limited. Specifically, there has been no research that explores strategy modes from a marketing environment perspective. Given that research at the intersection of marketing and management disciplines has often produced mutually beneficial, rich insights, we approach strategy modes from a product-market perspective and examine the normative appropriateness of different strategy modes with reference to firms\u27 external and internal environments. The research also explores the relevance and value of combining various strategy modes in regard to different stages of the product-market life cycle. In exploring strategy modes and their combinatory influences from a product-market perspective, we develop specific propositions. The paper concludes with a discussion of implications for academics and practitioners

Comparative study of change of HbA1c with voglibose and teneligliptin on ongoing metformin monotherapy

Background: Metformin is a biguanide used as first line treatment of type 2 diabetes mellitus. When Metformin alone is unable to control glycaemic status properly then additional drug needs to be added. Some of the additional drugs reduce primarily fasting blood sugar (FBS) and some reduce post prandial blood sugar (PPBS). Voglibose and Teneligliptin are primarily capable of reducing PPBS. Overall hyperglycaemia is also controlled by these drugs. In this background the present study was planned for comparative study of Voglibose and Teneligliptin to reduce HbA1c ongoing Metformin monotherapy. Materials & Methods: It was a hospital based longitudinal interventional study among patients attending General Medicine Outpatient Department (OPD) of a Medical College, East Medinipur, West Bengal with uncontrolled hyperglycemia and whose HbA1c was above 7 but up to 10% and PPBS above 200mg/dl. One group of patients was given voglibose 0.3mg TDS and another group of patients were given teneligliptin 20mg BD in addition to previous dose of metformin. After 12 weeks of starting additional drug again HbA1c level was assessed for each patient. Results: It was found that mean HbA1c level at the beginning was 8.89% for voglibose group and 8.83% for teneligliptin group. There was no significant difference between these two. After 12 weeks of therapy the mean HbA1c level of voglibose group was significantly higher than teneligliptin group. However both groups showed significant reduction of HbA1c as compared to starting. Conclusion: The study highlights the ability to reduce HbA1c is more with teneligliptin 20mg BD than voglibose 0.3mg TDS