1,509 research outputs found

    Sometimes magic

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    Oktrivanje funkcionalno sličnog koda zanimljiv je problem te njegovo rješenje može pomoći u raznim područjima poput detekcije zlonamjernih programa. U ovom radu predložen je algoritam za otkrivanje sličnosti koji koristi sažimanje određenih značajki Android izvršnih datoteka. Postoje četiri inačice algoritma koje s različitom preciznošću pronalaze funkcionalno slične Android primjenske programe. Provedeno je ispitivanje i analiza na skupu od 50000 Android primjen- skih programa. Algoritam je postigao vrlo dobre rezultate.Detection of functionally similar code is an interesting problem and it’s solution could be valuable to many different areas, one of which is malware detection. In this thesis, new algorithm for detection of similar code is proposed which hashes particular Android executable’s features. There are four versions of algorithm detecting similar Android applications with different precisions. Testing and analysis were conducted on set of 50000 Android applications. Algorithm achieved very good results

    Perspectives of Occupational Therapy Practitioners on Benefits and Barriers on Providing Occupational Therapy Services via Telehealth

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    The purpose of this project is to gain a better understanding of the provider’s perspectives about the strengths and barriers of occupational therapy (OT) services provided via telehealth. Based on the evidence that will be collected through surveys and interviews, this research can help determine specific factors on whether or not therapist choose to provide services through telehealth. Centered around those perspectives of telehealth, the results can help explore more in depth on the issues and concerns therapists have regarding telehealth as a service delivery model

    Sometimes magic

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    Discovery and development of novel inhibitors for the kinase Pim-1 and G-Protein Coupled Receptor Smoothened

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    Investigation of the cause of disease is no easy business. This is particularly so when one reflects upon the lessons taught us in antiquity. Prior to the beginning of the last century, diagnosis and treatment of diseases such as cancers was so bereft of hope that there was little physicians could offer in the way of comfort, let alone treatment. One of the major insights from investigations into cancers this century has been that those involved in research leading to treatments are not dealing with a singular malady but multiple families of diseases with different mechanisms and modes of action. Therefore, despite the end game being similar in cancers, that of uncontrolled growth and replication leading to cellular dysfunction, different diseases require different approaches in targeting them. This leads us to a particular broad treatment approach, that of drug design. A drug is, in the classical sense, a small molecule that, upon introduction into the body, interacts with biochemical targets to induce a wider biological effect, ideally with both an intended target and intended effect. The conceptual basis underpinning this `lock-and-key' paradigm was elucidated over a century ago and the primary occupation of those involved in biochemical research has been to determine as much information as possible about both of these protein locks and drug keys. And, as inferred from the paradigm, molecular shape is all-important in determining and controlling action against the most important locks with the most potent and specific keys. The two most important target classes in drug discovery for some time have been protein kinases and G Protein-Coupled Receptors (GPCRs). Both classes of proteins are large families that perform very different tasks within the body. Kinases activate and inactive many cellular processes by catalysing the transfer of a phosphate group from Adenosine Tri-Phosphate (ATP) to other targets. GPCRs perform the job of interacting with chemical signals and communicating them into a biological response. Dysfunction in both types of proteins in certain cells can lead to a loss of biological control and, ultimately, a cancer. Both of kinases and GPCRs have entirely different chemical structures so structural knowledge therefore becomes crucial in any approach targeting cells where dysfunction has occurred. Thus, for this thesis, a member from each class was investigated using a combination of structural approaches. From the kinase class, the kinase Proviral Integration site for MuLV (Pim-1) and from the GPCR class, the cell membrane-bound Smoothened receptor (SMO). The kinase \pimone\ was the target of various approaches in \autoref{chap:three}. Although a heavily studied target from the mid-2000's, there is a paucity of inhibitors targeting residues more remote from structural characteristics that define kinases. Further limiting extension possibilities is that \pimone\ is constitutively active so no inhibitors targeting an inactive state are possible. An initial project (\pone) used the known binding properties of small molecules, or, `fragments' to elucidate structural and dynamic information useful for targeting \pimone. This was followed by three projects, all with the goal of inhibitor discovery, all with different foci. In \ptwo, fragment binding modes from \pone\ provided the basis for the extension and development of drug-like inhibitors with a focus on synthetic feasibility. In contrast, inhibitors were found in \pthree\ via a large-scale public dataset of purchasable molecules that possess drug-like properties. Finally, \pfour\ took the truncated form of a particularly attractive fragment from \pone\ that was crystallised with \pimone, verified its binding mode and then generated extensions with, again, a focus on synthetic feasibility. The GPCR \smo\ has fewer molecular studies and much about its structural behaviour remains unknown. As the most `druggable' protein in the Hedgehog pathway, structural studies have primarily focussed on stabilising its inactive state to prevent signal transduction. Allied to this is that there are generally few inhibitors for \smo\ and the drugs for cancers related to its dysfunction are vulnerable to mutations that significantly reduce their effectiveness or abrogate it entirely. The elucidation of structural information in therefore of high priority. An initial study attempting to identify an unknown molecule from prior experiments led to insights regarding binding characteristics of specific moieties. This was particularly important to understand not just where favourable moieties bind but also sections of the \smo\ binding pocket with unfavourable binding. In both subsequent virtual screens performed in Chapter 4, the primary aim was to find new drug-like inhibitors of \smo\ using large public datasets of commercially-available molecules. The initial screen retrieved relatively few inhibitors so the binding pocket was modified to find a structural state more amenable to small molecule binding. These modifications led to a significant number of new, chemically novel inhibitors for \smo, some structural information useful for future inhibitors and the elucidation of structure-activity relationships useful for inhibitor design. This underpins the idea that structural information is of critical importance in the discovery and design of molecular inhibitors

    Taking Tasers Seriously: The Need for Better Regulation of Stun Guns in New York

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    This report analyzes 851 Taser incident reports from eight police departments across the state as well as 10 departments' policies and guidelines for using the weapons, which deliver up to 50,000 volts of electricity and have caused the deaths of more than a dozen New Yorkers in recent years. The report concludes that police officers throughout New York State are consistently misusing and overusing Tasers

    Perspectives of Occupational Therapists on Telehealth

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    The purpose of this project is to gain a better understanding of the provider’s perspectives about the strengths and barriers of OT services provided via telehealth. Based on the evidence that will be collected through surveys and interviews, it can help determine specific factors on whether or not therapist choose to provide services through telehealth. Centered around those perspectives of telehealth, the results can help explore more in depth on the issues and concerns therapists have when it comes to telehealth as a service delivery model.https://soar.usa.edu/casmfall2019/1010/thumbnail.jp

    Identification and Management of Scotch Thistle (Onopordum acanthium L.) in Pastures, Rangelands, and Non-Crop Settings

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    Scotch thistle (Onopordum acanthium) is an invasive species native to Eurasia. It was likely introduced into North America during the late 19th century (Young & Evans, 1969). Due to the plant’s size and prickles, a stand can damage pasture productivity, ruin campsites, or make trails nearly impassable. The thistle also outcompetes desirable plants and greatly reduces forage use by large animals. Since not all thistles are related or alike, it is essential to correctly identify Scotch thistle before making management decisions. This fact sheet provides information about identification, lifecycle and distribution, and management

    AFLOW-SYM: Platform for the complete, automatic and self-consistent symmetry analysis of crystals

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    Determination of the symmetry profile of structures is a persistent challenge in materials science. Results often vary amongst standard packages, hindering autonomous materials development by requiring continuous user attention and educated guesses. Here, we present a robust procedure for evaluating the complete suite of symmetry properties, featuring various representations for the point-, factor-, space groups, site symmetries, and Wyckoff positions. The protocol determines a system-specific mapping tolerance that yields symmetry operations entirely commensurate with fundamental crystallographic principles. The self consistent tolerance characterizes the effective spatial resolution of the reported atomic positions. The approach is compared with the most used programs and is successfully validated against the space group information provided for over 54,000 entries in the Inorganic Crystal Structure Database. Subsequently, a complete symmetry analysis is applied to all 1.7++ million entries of the AFLOW data repository. The AFLOW-SYM package has been implemented in, and made available for, public use through the automated, ab-initio\textit{ab-initio} framework AFLOW.Comment: 24 pages, 6 figure
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