Convergence of strain energy release rate components for edge-delaminated composite laminates

Strain energy release rates for edge delaminated composite laminates were obtained using quasi 3 dimensional finite element analysis. The problem of edge delamination at the -35/90 interfaces of an 8-ply composite laminate subjected to uniform axial strain was studied. The individual components of the strain energy release rates did not show convergence as the delamination tip elements were made smaller. In contrast, the total strain energy release rate converged and remained unchanged as the delamination tip elements were made smaller and agreed with that calculated using a classical laminated plate theory. The studies of the near field solutions for a delamination at an interface between two dissimilar isotropic or orthotropic plates showed that the imaginary part of the singularity is the cause of the nonconvergent behavior of the individual components. To evaluate the accuracy of the results, an 8-ply laminate with the delamination modeled in a thin resin layer, that exists between the -35 and 90 plies, was analyzed. Because the delamination exists in a homogeneous isotropic material, the oscillatory component of the singularity vanishes

An evaluation of potential locations for AROD ground stations

Airborne Range and Orbit Determination tracking stations potential locations evaluation and accuracy during early minutes of fligh

Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation

The proteome contains hundreds of proteins that in theory could be excellent therapeutic targets for the treatment of human diseases. However, many of these proteins are from functional classes that have never been validated as viable candidates for the development of small molecule inhibitors. Thus, to exploit fully the potential of the Human Genome Project to advance human medicine, there is a need to develop generic methods of inhibiting protein activity that do not rely on the target protein’s function. We previously demonstrated that a normally stable protein, methionine aminopeptidase-2 or MetAP-2, could be artificially targeted to an Skp1-Cullin-F-box (SCF) ubiquitin ligase complex for ubiquitination and degradation through a chimeric bridging molecule or Protac (proteolysis targeting chimeric molecule). This Protac consisted of an SCFß-TRCP-binding phosphopeptide derived from I{kappa}B{alpha} linked to ovalicin, which covalently binds MetAP-2. In this study, we employed this approach to target two different proteins, the estrogen (ER) and androgen (AR) receptors, which have been implicated in the progression of breast and prostate cancer, respectively. We show here that an estradiol-based Protac can enforce the ubiquitination and degradation of the {alpha} isoform of ER in vitro, and a dihydroxytestosterone-based Protac introduced into cells promotes the rapid disappearance of AR in a proteasome-dependent manner. Future improvements to this technology may yield a general approach to treat a number of human diseases, including cancer

Molecular Understanding and Modern Application of Traditional Medicines: Triumphs and Trials

Traditional medicines provide fertile ground for modern drug development, but first they must pass along a pathway of discovery, isolation, and mechanistic studies before eventual deployment in the clinic. Here, we highlight the challenges along this route, focusing on the compounds artemisinin, triptolide, celastrol, capsaicin, and curcumin

Timber composite floor beams under 2 years lon-term load

The long-term behaviour of composite beams is characterised by the response of its component parts (flanges and webs) to load, moisture content, temperature and relative humidity of the environment. This paper reports the results of a two years long-term test on two 6 m span composite floor beams made of laminated veneer lumber (LVL) under service load performed in an indoor, semi-controlled, and unheated environment. The environmental conditions were characterized by artificially induced cyclic air humidity with quasi-constant temperature. These conditions can be characterized as reasonably severe and presumably close to service class 3 according to Eurocode 5. During the test, the mid-span deflection, moisture content and air humidity were monitored. The paper recommends a creep factor for design of timber composite beams in severe environmental conditions

Tension perpendicular to grain strength of wood, Laminated Veneer Lumber (LVL), and Cross-Banded LVL (LVL-C)

Recent experimental tests carried out on structural timber members have highlighted the importance of tension perpendicular to grain strength, particularly in beams with holes and notches, in connection regions, in curved beams, and in post-tensioned timber frames. Innovative engineered wood products such as Cross Banded Laminated Veneer Lumber (LVL-C) have been introduced into the market specifically to improve the perpendicular to grain properties of normal Laminated Veneer Lumber (LVL). This paper reports on tests that were performed at the University of Canterbury using specimens of sawn timber Radiata Pine, LVL and LVL-C. The perpendicular to grain tension strengths of LVL was generally lower than those for sawn timber, but the LVL-C showed a significantly improved strength. The paper also compares the experimental results with strengths predicted using both coupled elastic Finite Element Method (FEM) and Linear Elastic Fracture Mechanics (LEFM) models. These models were found to predict the average strength with reasonable accuracy. © 2011 Taylor & Francis Group, London

Design and applications of bifunctional small molecules: Why two heads are better than one

Induction of protein−protein interactions is a daunting challenge, but recent studies show promise for small molecules that specifically bring two or more protein molecules together for enhanced or novel biological effect. The first such bifunctional molecules were the rapamycin- and FK506-based “chemical inducers of dimerization”, but the field has since expanded with new molecules and new applications in chemical genetics and cell biology. Examples include coumermycin-mediated gyrase B dimerization, proteolysis targeting chimeric molecules (PROTACs), drug hybrids, and strategies for exploiting multivalency in toxin binding and antibody recruitment. This Review discusses these and other advances in the design and use of bifunctional small molecules and potential strategies for future systems

Competing Perspectives During Organizational Socialization on the Role of Certified Athletic Trainers in High School Settings

When certified athletic trainers (ATCs) enter a workplace, their potential for professional effectiveness is affected by a number of factors, including the individual\u27s ability to put acquired knowledge, skills, and attitudes into practice. This ability may be influenced by the preconceived attitudes and expectations of athletes, athletes\u27 parents, athletic directors, physical therapists, physicians, and coaches. Objective: To examine the perspectives of high school coaches and ATCs toward the ATC\u27s role in the high school setting by looking at 3 questions: (1) What are coaches\u27 expectations of ATCs during different phases of a sport season? (2) What do ATCs perceive their role to be during different phases of a season? and (3) How do coaches\u27 expectations compare with ATCs\u27 expectations

Triptolide Directly Inhibits dCTP Pyrophosphatase

Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti-inflammatory, antifertility, and antipolycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide-interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide