Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site.

The structure of a folded core of IL-16 is similar to that of intracellular protein modules called PDZ domains. IL-16 is thus the first extracellular protein found to have a PDZ-like fold. However, it does not exhibit normal peptide binding properties of PDZ domains. This is due to alterations of the structure at the 'PDZ-like binding site' of IL-16 (the GLGF cleft): the GLGF cleft of IL-16 is much smaller than those of PDZ-domains and is additionally blocked with a tryptophan side chain at its center. Our experiments indicate also that IL-16 nonspecifically aggregates in solution; but formation of a homo-tetrameric protein is not required, in contrast to previous suggestions, for its chemo-attractant activity

Purtscher-like retinopathy following valsalva maneuver effect: case report

<p>Abstract</p> <p>Introduction</p> <p>Purtscher's retinopathy is a rare condition that is noted in cases related to various types of trauma. The characteristic finding in the fundus is the presence of multiple Purtscher flecken. Purtscher-like retinopathy has a similar presentation in the fundus, but without an association with trauma.</p> <p>Case presentation</p> <p>A 43-year old Malay man presented with a sudden onset of central foggy vision in the left eye after holding his breath for two minutes while catching a falling object. It was not associated with floaters, flashes of light, or head trauma. His vision in the right eye was 6/6, and in his left eye it was finger counting. He had bilateral temporal sub-conjunctival hemorrhages. An examination of his left fundus revealed multiple white cotton wool spots and dot-blot retinal hemorrhages with diffuse retinal edema at the posterior pole. His right fundus was noted to have only mild temporal peri-papillary edema associated with a few dot-blot hemorrhages. Fundus fluorescein angiography showed good arterial perfusion and no evidence of leaking or neo-vascularization. A diagnosis of Purtscher-like retinopathy was made, and the patient was treated with indomethacin tablets for six weeks. At his six-week follow-up examination, his left eye visual acuity had improved to 6/12. His bilateral sub-conjunctival hemorrhage had resolved. His left fundus showed residual multiple cotton wool spots and reduced retinal edema.</p> <p>Conclusions</p> <p>Treatment with non-steroidal anti-inflammatory drugs seems to be effective in reducing edema in patients with Purtscher-like retinopathy.</p

Optimized Inhibitors of MDM2 via an Attempted Protein-Templated Reductive Amination

Innovative and efficient hit-identification techniques are required to accelerate drug discovery. Protein-templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein-templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists. Herein, we present our attempts to use a protein-templated reductive amination to target protein-protein interactions (PPIs), a challenging class of drug targets. We address a flexible pocket, which is difficult to achieve by structure-based drug design. After careful analysis we did not find one of the possible products in the kinetic target-guided synthesis (KTGS) approach, however subsequent synthesis and biochemical evaluation of each library member demonstrated that all the obtained molecules inhibit MDM2. The most potent library member (Ki=0.095 μm) identified is almost as active as Nutlin-3, a potent inhibitor of the p53-MDM2 PPI

Enabling large-scale design, synthesis and validation of small molecule protein-protein antagonists

Although there is no shortage of potential drug targets, there are only a handful known low-molecular-weight inhibitors of protein-protein interactions (PPIs). One problem is that current efforts are dominated by low-yield high-throughput screening, whose rigid framework is not suitable for the diverse chemotypes present in PPIs. Here, we developed a novel pharmacophore-based interactive screening technology that builds on the role anchor residues, or deeply buried hot spots, have in PPIs, and redesigns these entry points with anchor-biased virtual multicomponent reactions, delivering tens of millions of readily synthesizable novel compounds. Application of this approach to the MDM2/p53 cancer target led to high hit rates, resulting in a large and diverse set of confirmed inhibitors, and co-crystal structures validate the designed compounds. Our unique open-access technology promises to expand chemical space and the exploration of the human interactome by leveraging in-house small-scale assays and user-friendly chemistry to rationally design ligands for PPIs with known structure. © 2012 Koes et al

Artificial intelligence (AI): multidisciplinary perspectives on emerging challenges, opportunities, and agenda for research and practice

As far back as the industrial revolution, great leaps in technical innovation succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision making engendering new opportunities for continued innovation. The impact of AI is significant, with industries ranging from: finance, retail, healthcare, manufacturing, supply chain and logistics all set to be disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: technological, business and management, science and technology, government and public sector. The research offers significant and timely insight to AI technology and its impact on the future of industry and society in general

Construction diagnosting using digital image correlation

W artykule zaprezentowano zastosowanie bezkontaktowych metod optycznych do analizy kształtu ugięcia konstrukcji. W tym celu za pomocą macierzy homografii oraz współczynnika korelacji wyznaczono przemieszczenia reprezentujące deformacje konstrukcji w oparciu o obrazy konstrukcji przed i po deformacji uzyskane z dowolnie umiejscowionej kamery. Zastosowanie technik podpikselowych umożliwiło zwiększenie dokładności pomiarowej otrzymanego pola przemieszczeń analizowanego obiektu. Opracowaną metodykę oraz procedury zaimplementowano oraz przetestowano w środowisku programowym MATLAB.In the paper the application of non-contact optical methods for a construction deformation analysis was presented. Homography matrix and correlation coefficient were employed by the means of two construction images: state before and after deformation in order to obtain displacements field. It represents a shape deformation of the analyzed construction. Introduced subpixel techniques allowed measurement accuracy increasing for calculated displacement field. Developed methods and procedures were implemented and tested in programming environment - MATLAB

Application of vision techniques for construction state monitoring

W pracy dokonano przeglądu dostępnych na rynku trójwymiarowych wizyjnych systemów pomiarowych. Przedstawiono koncepcję nowego systemu wizyjnego do pomiaru deformacji i struktury obiektów inżynierii lądowej oraz pomiaru przebiegów drgań, oraz wizualizacji operacyjnych postaci drgań. W artykule przedstawiono wstępne wyniki testów metody pomiaru ugięcia konstrukcji z wykorzystaniem współczynnika korelacji obrazów na stanowisku laboratoryjnym oraz na obiektach rzeczywistych.Review of 3D vision measurement systems available on the market is presented in the paper. A concept of new vision systems dedicat-ed to measurements of deformation and geometry of civil engineer-ing objects as well as vibrations of structures and visualization of operational shape modes is introduced. The first system described in the paper enables in-plane defection course to be obtained by means of homography matrix and digital image correlation. As a result the deflection field can be computed from two images of the structure acquired from two different points in space. Epipolar geometry methods were introduced in order to provide 3D deformation's of the structures. The second system enables obtaining amplitudes of vibrations of analyzed scene objects along with their structure based upon data derived from one or two calibrated digital fast cameras. For this purpose techniques based on epipolar geometry are employed. Courses of vibrations computed by the system can be used as data for experimental modal analysis. Mode shapes visualization can be carried out by a high resolution digital camera and developed lock-in techniques. Results of preliminary tests of 2D vision deflection measurement method using digital image correlation coefficient in the laboratory as well as on the real construction are presented