Computational approaches for the design of peptides with anti-breast cancer properties

Background: Breast cancer is the most common cancer among women. Tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment, yet many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Therefore, scientists are searching for breast cancer drugs that have different molecular targets. Methodology: Recently, a computational approach was used to successfully design peptides that are new lead compounds against breast cancer. We used replica exchange molecular dynamics to predict the structure and dynamics of active peptides, leading to the discovery of smaller bioactive peptides. Conclusions: These analogs inhibit estrogen-dependent cell growth in a mouse uterine growth assay, a test showing reliable correlation with human breast cancer inhibition. We outline the computational methods that were tried and used along with the experimental information that led to the successful completion of this research.

Comparison of biolimus eluted from an erodible stent coating with bare metal stents in acute ST-elevation myocardial infarction (COMFORTABLE AMI trial): rationale and design

Compared with bare metal stents (BMS), early generation drug-eluting stents (DES) reduce the risk of revascularisation in patients with ST-elevation myocardial infarction (STEMI) at the expense of an increased risk of very late stent thrombosis (ST). Durable polymer coatings for controlled drug release have been identified as a potential trigger for these late adverse events and this has led to the development of newer generation DES with durable and biodegradable polymer surface coatings with improved biocompatibility. In a recent all-comers trial, biolimus-eluting stents with a biodegradable polymer surface coating were found to reduce the risk of very late ST by 80% compared with sirolimus-eluting stents with durable polymer, which also translated into a lower risk of cardiac death and myocardial infarction (MI) beyond one year.

Influence of Surface Roughness on Mechanical Properties of Two Computer-aided Design/Computer-aided Manufacturing (CAD/CAM) Ceramic Materials

SUMMARY The aim of this study was to evaluate the influence of surface roughness on surface hardness (Vickers; VHN), elastic modulus (EM), and flexural strength (FLS) of two computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic materials. One hundred sixty-two samples of VITABLOCS Mark II (VMII) and 162 samples of IPS Empress CAD (IPS) were ground according to six standardized protocols producing decreasing surface roughnesses (n=27/group): grinding with 1) silicon carbide (SiC) paper #80, 2) SiC paper #120, 3) SiC paper #220, 4) SiC paper #320, 5) SiC paper #500, and 6) SiC paper #1000. Surface roughness (Ra/Rz) was measured with a surface roughness meter, VHN and EM with a hardness indentation device, and FLS with a three-point bending test. To test for a correlation between surface roughness (Ra/Rz) and VHN, EM, or FLS, Spearman rank correlation coefficients were calculated. The decrease in surface roughness led to an increase in VHN from (VMII/IPS; medians) 263.7/256.5 VHN to 646.8/601.5 VHN, an increase in EM from 45.4/41.0 GPa to 66.8/58.4 GPa, and an increase in FLS from 49.5/44.3 MPa to 73.0/97.2 MPa. For both ceramic materials, Spearman rank correlation coefficients showed a strong negative correlation between surface roughness (Ra/Rz) and VHN or EM and a moderate negative correlation between Ra/Rz and FLS. In conclusion, a decrease in surface roughness generally improved the mechanical properties of the CAD/CAM ceramic materials tested. However, FLS was less influenced by surface roughness than expected.

Looking at the effectiveness of an earth science unit designed using the Understanding by Design process

This report shares my efforts in developing a solid unit of instruction that has a clear focus on student outcomes. I have been a teacher for 20 years and have been writing and revising curricula for much of that time. However, most has been developed without the benefit of current research on how students learn and did not focus on what and how students are learning. My journey as a teacher has involved a lot of trial and error. My traditional method of teaching is to look at the benchmarks (now content expectations) to see what needs to be covered. My unit consists of having students read the appropriate sections in the textbook, complete work sheets, watch a video, and take some notes. I try to include at least one hands-on activity, one or more quizzes, and the traditional end-of-unit test consisting mostly of multiple choice questions I find in the textbook. I try to be engaging, make the lessons fun, and hope that at the end of the unit my students get whatever concepts I‘ve presented so that we can move on to the next topic. I want to increase students‘ understanding of science concepts and their ability to connect understanding to the real-world. However, sometimes I feel that my lessons are missing something. For a long time I have wanted to develop a unit of instruction that I know is an effective tool for the teaching and learning of science. In this report, I describe my efforts to reform my curricula using the “Understanding by Design” process. I want to see if this style of curriculum design will help me be a more effective teacher and if it will lead to an increase in student learning. My hypothesis is that this new (for me) approach to teaching will lead to increased understanding of science concepts among students because it is based on purposefully thinking about learning targets based on “big ideas” in science. For my reformed curricula I incorporate lessons from several outstanding programs I‘ve been involved with including EpiCenter (Purdue University), Incorporated Research Institutions for Seismology (IRIS), the Master of Science Program in Applied Science Education at Michigan Technological University, and the Michigan Association for Computer Users in Learning (MACUL). In this report, I present the methodology on how I developed a new unit of instruction based on the Understanding by Design process. I present several lessons and learning plans I‘ve developed for the unit that follow the 5E Learning Cycle as appendices at the end of this report. I also include the results of pilot testing of one of lessons. Although the lesson I pilot-tested was not as successful in increasing student learning outcomes as I had anticipated, the development process I followed was helpful in that it required me to focus on important concepts. Conducting the pilot test was also helpful to me because it led me to identify ways in which I could improve upon the lesson in the future.

No surgical innovation without evaluation: the IDEAL recommendations

Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.

Zukunftspotential durch Design und RM

Im Bereich Medical Design spielen eine hohe Funktionalität und eine angenehme Handhabung eine grosse Rolle. In den Engineering-Projekten der Erdmann Design AG werden kühne Ideen in den Raum gesetzt die das Klima für Innovationen fördern. „Innovation entsteht aus elementarer Neugier und Lust auf eine bessere Zukunft“, sagt Raimund Erdmann. „Wir beraten mit unseren Feed Forward Methoden Start-up Firmen, Kleinunternehmen wie auch etliche, börsenkotierte, international aktive Unternehmen. Und das für excellentes Industrial Design, Corporate Design und Design Management“ mit den überzeugenden Möglichkeiten des Rapid Manufacturing.Im Bereich Medical Design spielen eine hohe Funktionalität und eine angenehme Handhabung eine grosse Rolle. In den Engineering-Projekten der Erdmann Design AG werden kühne Ideen in den Raum gesetzt die das Klima für Innovationen fördern. „Innovation entsteht aus elementarer Neugier und Lust auf eine bessere Zukunft“, sagt Raimund Erdmann. „Wir beraten mit unseren Feed Forward Methoden Start-up Firmen, Kleinunternehmen wie auch etliche, börsenkotierte, international aktive Unternehmen. Und das für excellentes Industrial Design, Corporate Design und Design Management“ mit den überzeugenden Möglichkeiten des Rapid Manufacturing.

Knowledge Exchange in Intra-Organizational Innovation Communities: The Role of Cognitive and Affective States

Many aspects in the area of designing platforms for intra-organizational innovation communities are not well understood. In this article, we examine the impact of technologically induced psychological factors on knowledge exchange in such communities. Using two experimental pretest-posttest experiments, we find that the implementation of (i) technologically induced self-efficacy (expressed by a ‘hurray’ message) and (ii) technologically induced positive affect (expressed by playing some 30 seconds of rock-‘n’-roll music) in the design of the platform results in an influential increase of knowledge exchange. Importantly, the studies suggest that the integration of technologically induced self-efficacy leads to a higher extent of knowledge exchange than technologically induced positive affect. The implications of these results for future research and practice as well as for the design of a platform for such communities are discussed.

Not for Designers: On the Inadequacies of EU Design Law and How to Fix It

Design rights represent an interesting example of how the EU legislature has successfully regulated an otherwise heterogeneous field of law. Yet this type of protection is not for all. The tools created by EU intervention have been drafted paying much more attention to the industry sector rather than to designers themselves. In particular, modern, digitally based, individual or small-sized, 3D printing, open designers and their needs are largely neglected by such legislation. There is obviously nothing wrong in drafting legal tools around the needs of an industrial sector with an important role in the EU economy, on the contrary, this is a legitimate and good decision of industrial policy. However, good legislation should be fair, balanced, and (technologically) neutral in order to offer suitable solutions to all the players in the market, and all the citizens in the society, without discriminating the smallest or the newest: the cost would be to stifle innovation. The use of printing machinery to manufacture physical objects created digitally thanks to computer programs such as Computer-Aided Design (CAD) software has been in place for quite a few years, and it is actually the standard in many industrial fields, from aeronautics to home furniture. The change in recent years that has the potential to be a paradigm-shifting factor is a combination between the opularization of such technologies (price, size, usability, quality) and the diffusion of a culture based on access to and reuse of knowledge. We will call this blend Open Design. It is probably still too early, however, to say whether 3D printing will be used in the future to refer to a major event in human history, or instead will be relegated to a lonely Wikipedia entry similarly to ³Betamax² (copyright scholars are familiar with it for other reasons). It is not too early, however, to develop a legal analysis that will hopefully contribute to clarifying the major issues found in current EU design law structure, why many modern open designers will probably find better protection in copyright, and whether they can successfully rely on open licenses to achieve their goals. With regard to the latter point, we will use Creative Commons (CC) licenses to test our hypothesis due to their unique characteristic to be modular, i.e. to have different license elements (clauses) that licensors can choose in order to adapt the license to their own needs.”

Light curing through glass ceramics with a second- and a third-generation LED curing unit: effect of curing mode on the degree of conversion of dual-curing resin cements

Objectives The aim of this study was to measure the degree of conversion (DC) of five dual-curing resin cements after different curing modes with a second- and a third-generation light-emitting diode (LED) curing unit. Additionally, irradiance of both light curing units was measured at increasing distances and through discs of two glass ceramics for computer-aided design/manufacturing (CAD/CAM). Materials and methods Irradiance and spectra of the Elipar FreeLight 2 (Standard Mode (SM)) and of the VALO light curing unit (High Power Mode (HPM) and Xtra Power Mode (XPM)) were measured with a MARC radiometer. Irradiance was measured at increasing distances (control) and through discs (1.5 to 6 mm thickness) of IPS Empress CAD and IPS e.max CAD. DC of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA was measured with an attenuated total reflectance–Fourier transform infrared spectrometer when self-cured (negative control) or light cured in SM for 40 s, HPM for 32 s, or XPM for 18 s. Light curing was performed directly (positive control) or through discs of either 1.5- or 3-mm thickness of IPS Empress CAD or IPS e.max CAD. DC was analysed with Kruskal–Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). Results Maximum irradiances were 1,545 mW/cm2 (SM), 2,179 mW/cm2 (HPM), and 4,156 mW/cm2 (XPM), and all irradiances decreased by >80 % through discs of 1.5 mm, ≥95 % through 3 mm, and up to >99 % through 6 mm. Generally, self-curing resulted in the lowest DC. For some cements, direct light curing did not result in higher DC compared to when light cured through ceramic discs. For other cements, light curing through ceramic discs of 3 mm generally reduced DC. Conclusions Light curing was favourable for dual-curing cements. Some cements were more susceptible to variations in curing mode than others. Clinical relevance When light curing a given cement, the higher irradiances of the third-generation LED curing unit resulted in similar DC compared to the second-generation one, though at shorter light curing times.

Semantic Methods for Intelligent Distributed Design Environments

Continuous advancements in technology have led to increasingly comprehensive and distributed product development processes while in pursuit of improved products at reduced costs. Information associated with these products is ever changing, and structured frameworks have become integral to managing such fluid information. Ontologies and the Semantic Web have emerged as key alternatives for capturing product knowledge in both a human-readable and computable manner. The primary and conclusive focus of this research is to characterize relationships formed within methodically developed distributed design knowledge frameworks to ultimately provide a pervasive real-time awareness in distributed design processes. Utilizing formal logics in the form of the Semantic Web’s OWL and SWRL, causal relationships are expressed to guide and facilitate knowledge acquisition as well as identify contradictions between knowledge in a knowledge base. To improve the efficiency during both the development and operational phases of these “intelligent” frameworks, a semantic relatedness algorithm is designed specifically to identify and rank underlying relationships within product development processes. After reviewing several semantic relatedness measures, three techniques, including a novel meronomic technique, are combined to create AIERO, the Algorithm for Identifying Engineering Relationships in Ontologies. In determining its applicability and accuracy, AIERO was applied to three separate, independently developed ontologies. The results indicate AIERO is capable of consistently returning relatedness values one would intuitively expect. To assess the effectiveness of AIERO in exposing underlying causal relationships across product development platforms, a case study involving the development of an industry-inspired printed circuit board (PCB) is presented. After instantiating the PCB knowledge base and developing an initial set of rules, FIDOE, the Framework for Intelligent Distributed Ontologies in Engineering, was employed to identify additional causal relationships through extensional relatedness measurements. In a conclusive PCB redesign, the resulting “intelligent” framework demonstrates its ability to pass values between instances, identify inconsistencies amongst instantiated knowledge, and identify conflicting values within product development frameworks. The results highlight how the introduced semantic methods can enhance the current knowledge acquisition, knowledge management, and knowledge validation capabilities of traditional knowledge bases.

Methodology for the design of offshore wind farms

Although still in an early stage, offshore wind development is now characterized by a boom process. This leads to the necessity of applying an integral management model for the design of offshore wind facilities, being the purpose of the model to achieve technical, economical and environmental viability, all within a sustainable development framework. The foregoing led to the research project exposed in this paper, consisting of drawing up an offshore wind farms methodological proposal; this methodology has a global and/or general nature or point of view whilst searching for optimization of the overall process of operations leading to the design of this type of installations and establishing collated theoretical bases for the further development of management tools. This methodological proposal follows a classical engineering thought scheme: it begins with the alternatives study, and ends with the detailed design. With this in mind, the paper includes the following sections: introduction, methodology used for the research project, conditioning factors, methodological proposal for the design of offshore wind farms, checking the methodological proposal, and conclusions

Architectural design and construction costs, tools towards territorial sustainability

This paper is presented in CIB: Management and Innovation Sustainable Built Environment 2011, as the study and analysis of the residential model of a rural area from the Iberian Peninsula, specifically applied to the case of the province of Cáceres, in the autonomous region of Extremadura, in Spain. To this end, from a database made up of building projects whose real costs are known, it is intended to establish the links of the different parameters studied through the corresponding functions of statistical analysis. One of the main objectives of this process is constituted by the possibility of establishing those design variables of higher economic importance, so as to keep an economic control of these parameters, generally geometrical and typological, from the very start of the project. And, in general, a higher optimization of resources in the construction of dwellings in the rural environment from their design is intended.

Migration to an a on-line laboatory in mechanical engineering. The case of a cam-follower design practice.

The European Higher Education Area (EHEA) has leaded to a change in the way the subjects are taught. One of the more important aspects of the EHEA is to support the autonomous study of the students. Taking into account this new approach, the virtual laboratory of the subject Mechanisms of the Aeronautical studies at the Technical University of Madrid is being migrated to an on-line scheme. This virtual laboratory consist on two practices: the design of cam-follower mechanisms and the design of trains of gears. Both practices are software applications that, in the current situation, need to be installed on each computer and the students carry out the practice at the computer classroom of the school under the supervision of a teacher. During this year the design of cam-follower mechanisms practice has been moved to a web application using Java and the Google Development Toolkit. In this practice the students has to design and study the running of a cam to perform a specific displacement diagram with a selected follower taking into account that the mechanism must be able to work properly at high speed regime. The practice has maintained its objectives in the new platform but to take advantage of the new methodology and try to avoid the inconveniences that the previous version had shown. Once the new practice has been ready, a pilot study has been carried out to compare both approaches: on-line and in-lab. This paper shows the adaptation of the cam and follower practice to an on-line methodology. Both practices are described and the changes that has been done to the initial one are shown. They are compared and the weak and strong points of each one are analyzed. Finally we explain the pilot study carried out, the students impression and the results obtained.