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Experimental Active-Site Mapping by Fragments - Hot Spots Remote from the Catalytic Center of Endothiapepsin

Successful optimization of a given lead scaffold requires thorough binding-site mapping of the target protein particular in regions remote from the catalytic center where high conservation across protein families is given. We screened a 361-entry fragment library for binding to the aspartic protease endothiapepsin by crystallography. This enzyme is frequently used as surrogate for the design of re

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand struct

High-Throughput Crystallography : Reliable and Efficient Identification of Fragment Hits

Today the identification of lead structures for drug development often starts from small fragment-like molecules raising the chances to find compounds that successfully pass clinical trials. At the heart of the screening for fragments binding to a specific target, crystallography delivers structural information essential for subsequent drug design. While it is common to search for bound ligands in

Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits : A Case Study

Fragment-based lead discovery (FBLD) has become a pillar in drug development. Typical applications of this method comprise at least two biophysical screens as prefilter and a follow-up crystallographic experiment on a subset of fragments. Clearly, structural information is pivotal in FBLD, but a key question is whether such a screening cascade strategy will retrieve the majority of fragment-bound

Förtrollande riter i det offentliga rummet : hur designas den lyckade individen?

Denna artikel diskuterar en ny form av snabbt expanderande praktiker från tidigt 2000-tal och som erbjuds av privata företag eller entreprenörer (lekmannaterapeuter). I fokus står självförverkligande och helande. Jag har med hjälp av verktyg från Ritual Studies valt att analysera dessa praktiker som en form av individ-centrerade riter som designas för att lindra smärta och lågt självförtroende förThis article discusses a new form of practices which are offered by private companies or entrepreneurs (layman therapists) whose practices focusing on self-development and healing rapidly expanded in the early 2000s in Sweden. I have chosen to analyze these practices from a Ritual Studies perspective as individual-centered rites designed to remedy ill health and low self-esteem and to build new, p

Cellular targets of HAMLET, their role in tumor cell death and therapeutic potential

Protein-lipid complexes have broad and specific effects against cancers of different origins. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a complex of partially unfolded α-lactalbumin and oleic acid that kills a wide range of tumor cells but leaves healthy differentiated cells unaffected. Therapeutic efficacy of HAMLET has been demonstrated in several animal models, without appa

Paradoxes of Local Government Reform in Post-Soviet Central Asia

This paper explores the context, problems, quality, and challenges of local governance in four Central Asian countries: Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan. The prime focus is on the question of whether local governments in this region perform their functions in an effective and efficient way. It looks at the four conditions – contextual, structural, institutional and human resource

Essays on Firms' Financing and Investment Decisions

This thesis analyses how the capital structures of financial and non-financial firms affect each other and how shocks in the financial sector affect investments in non-financial firms. The thesis consists of three self-contained essays.The first essay provides new evidence on the capital structure determinants of non-financial firms and contributes to the discussion concerning the effect of a regu

A Study on Energy Used to Deliver H.264/AVC and H.265/HEVC Video Content

We propose an end-to-end approach to describe the energy usage of video delivery within a content delivery framework, and use this to investigate the energy usage behavior of two popular coding schemes, namely, H.264/AVC and H.265/HEVC. Our study based on the proposed model is backed up by measurements of encoding and decoding energy usage of a sample video and shows that, from an end-to-end persp

Taxation of Partnership - Legal national reports for the Nordic Tax Research Council's annual meeting, 2015 in Aarhus

This joint report includes the five legal national reports on the taxation of partnership in the Nordic countries. The general contents of these reports are summarized and thoroughly analyzed in Liselotte Madsen’s General report, published in this issue of the NTaxJ. For additional information, details on legislative measures etc. we find it important, however, to also publish the national reports

Team Reasoning and Collective Intentionality

Different versions of the idea that individualism about agency is the root of standard game theoretical puzzles have been defended by Regan 1980, Bacharach (Research in Economics 53: 117–147, 1999), Hurley (Behavioral and Brain Sciences 26: 264–265, 2003), Sugden (Philosophical Explorations 6(3):165–181, 2003), and Tuomela 2013, among others. While collectivistic game theorists like Michael Bachar

Taxation of Partnership - Economic national reports for the Nordic Tax Research Council's annual meeting, 2015 in Aarhus

This joint report includes economic national reports on the taxation of partnership in the Nordic countries, except Denmark. The general contents of these reports are summarized and thoroughly analyzed in Anna Holst Birket-Smith’s General report, published in this issue of the NTaxJ. For additional information, details on legislative measures etc. we find it important, however, to also publish the

Book Reviews 2015

This section contains three book reviews. First the book Swedish Taxation, Development since 1862 is reviewed. This volume comprises six studies that examine the development of Swedish taxation from 1862 to 2013, and will likely be of great value in future Nordic tax research because of its comprehensiveness. The second review is about a book written in Swedish:Momsfri sjukvård (The VAT exemption

A Low-complexity Channel Shortening Receiver with Diversity Support for Evolved 2G Devices

The second generation (2G) cellular networks are the current workhorse for machine-to-machine (M2M) communications. Diversity in 2G devices can be present both in form of multiple receive branches and blind repetitions. In presence of diversity, intersymbol interference (ISI) equalization and co-channel interference (CCI) suppression are usually very complex. In this paper, we consider the improve

Applying landscape genetics to the microbial world

Landscape genetics, which explicitly quantifies landscape effects on gene flow and adaptation, has largely focused on macroorganisms, with little attention given to microor- ganisms. This is despite overwhelming evidence that microorganisms exhibit spatial genetic structuring in rela- tion to environmental variables. The increasing accessi- bility of genomic data has opened up the opportunity for

The Impact of Classroom Practices on Young Learners' Acquisition of Subject-Verb Agreement in Vietnam : a Pilot Study

Researchers have long emphasized the importance of classroominteraction for enhancing foreign language learning (Carroll 1967; Chihara& Oller, 1987; Krashen, Butler, Birkbaum, & Robertson 1978; Krashen &Seliger, 1976). This pilot study attempts to see how English teaching and learning methods in Vietnamese classrooms affect young learners’acquisition of English subject-verb agreement i