Cheaper Faster Drug Development Validated By The Repositioning Of Drugs Against Neglected Tropical Diseases.

There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist 'Eve' designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.

Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

Mycosis fungoides (MF) and Sezary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin`s lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. J Clin Oncol 29:2598-2607. (C) 2011 by American Society of Clinical Oncology

Non-classical error bounds in the central limit theorem

The classical central limit theorem states the uniform convergence of the distribution functions of the standardized sums of independent and identically distributed square integrable real-valued random variables to the standard normal distribution function. While first versions of the central limit theorem are already due to Moivre (1730) and Laplace (1812), a systematic study of this topic started at the beginning of the last century with the fundamental work of Lyapunov (1900, 1901). Meanwhile, extensions of the central limit theorem are available for a multitude of settings. This includes, e.g., Banach space valued random variables as well as substantial relaxations of the assumptions of independence and identical distributions. Furthermore, explicit error bounds are established and asymptotic expansions are employed to obtain better approximations. Classical error estimates like the famous bound of Berry and Esseen are stated in terms of absolute moments of the random summands and therefore do not reflect a potential closeness of the distributions of the single random summands to a normal distribution. Non-classical approaches take this issue into account by providing error estimates based on, e.g., pseudomoments. The latter field of investigation was initiated by work of Zolotarev in the 1960's and is still in its infancy compared to the development of the classical theory. For example, non-classical error bounds for asymptotic expansions seem not to be available up to now ...

Estudi d'inundabilitat de Calonge

Aquest és un projecte per fer un estudi d’inundabilitat de la zona de Calonge i Sant Antoni de Calonge per tal de reduir l’impacte que aquestes inundacions ocasionen. La realització de l’estudi és necessària ja que les inundacions a la zona són periòdiques i els efectes no disminueixen d’un episodi a l’altre, per tant, cal establir mesures correctores i/o minimitzadores per tal d’evitar la perillositat d’aquests efectes. Es tracta d’un projecte de final de Carrera, de 4rt de Ciències Ambientals, que va ser encarregat per l’Ajuntament de Calonge, l’Octubre del 2005 un cop finalitzats els greus episodis d’inundacions que tants de danys van ocasionar al terme municipal

Current multiple myeloma treatment strategies with novel agents: a European perspective.

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Nummi

Vastine Matti Vilppulan artikkeliin // Virittäjä 1983, s. 60-61

Sijamuotojen käytöstä suomenvenäjässä

Summary

Quaestio nostro saeculo inusitata : русское православие в тезисах Йоханнеса Ботвиди “Христиане ли Московиты?” (1620)

Den svenska pastorn Johannes Botvidi (1575-1635) försvarade år 1620 sitt verk Theses de quaestione, utrum Moschovitae sint Christiani (”Är Moskoviterna Kristna?”) vid en allmän disputation som ägde rum vid Akademin i Uppsala. Trots att Botvidis teser är centrala för den protestantiska synen på den ryska ortodoxin vid denna tid har verket inte studerats i detalj. Jag har läst Botvidis verk som en text där olika för tiden aktuella diskurser kommer till uttryck och där innehållet fokuseras ur olika synvinklar. Centrala för Botvidis teser är följande diskurser: i början av 1600-talet har i Europa redan etablerats en syn på moskoviten som den Andre, om vilken man berättar ”enligt vissa mönster”; en protestantisk kritik av ortodoxin har uppstått som en del av en bredare religiös diskurs; i stormakten Sverige uppfattar man sig ha en ny roll som ledare för den protestantiska världen med åtföljande ideologi och retorik; den skolastiska disputationen förutsätter en metod och retorik som i Botvidis teser har till syfte att ge auktoritet åt den svenska teologin. Min metod att studera Botvidis text försiggår således i ett diskurs-perspektiv, där språkliga strukturer och retoriska strategier inbyggda i texten tolkas inom ramen för den relevanta diskursen. Genom denna metod närmar jag mig målet för min utforskning – att förstå inte bara betydelsen av Botvidis text om moskoviternas religion utan också meningen med själva disputationen. Botvidis teser kontextualiseras i sin tid, vilket ger oss insikter i hur ett kulturmedvetande fungerar. Texten ”Är Moskoviterna Kristna?” framstår som ett mångfasetterat dokument som svarar på fler frågor än den som ställs i rubriken. Spännande i Botvidis text är också hur teologen Botvidi genom den medeltida skolastikens metoder lägger grunden för en toleransdiskurs.

Prosessiteollisuuden sekoittimen elinkaariarviointi

Työn tavoitteena oli tehdä elinkaariarviointi (LCA) prosessiteollisuuden sekoittimelle Helmix HF-80 ja analysoida LCA-tulokset, vaikutus ilmaston lämpenemisen potentiaalin (GWP) suhteen, sekä tutkia GWP-vaikutuksen pienentämisen mahdollisuuksia. Tutkittavan sekoittimen mahdolliset käyttökohteet ovat sellu- ja paperiteollisuus, raskaiden jätenesteiden käsittely, sekä muut teollisuusalueet, joissa käytetään tämän tyyppisiä laitteita. Työssä on muun muassa käsitelty sekoitusprosessit, sekoituslaitteiden tyypit, niiden rakenteiden ominaisuudet, käyttötarkoitus, toimintaperiaatteet, sekä sellu- ja paperi-teollisuudessa käytettävien sekoittimien yleiskatsaus. Työssä on myös kuvattu elinkaariarviointi (LCA) -menetelmä ja sen käyttötarkoitus. Tärkeimmistä tuloksista voi mainita sen, että sekoittimen (ilman säiliötä, sähkömoottoria ja vaihteistoa) kokoelinkaaren ilmastonlämpenemisen potentiaali (GWP) on noin 750 000 kg CO2-Equiv. Sekoittimen tuotanto- ja kierrätysaikana syntyy vain 1200 kg CO2-Equiv. ja suurin osa 748 000 kg CO2-Equiv. johtuu sähköenergian kulutuksesta käytön aikana. Käyttöajan vaikutusta voisi pienentää arvoksi 0 kg CO2-Equiv. käyttämällä pelkästään uusiutuvaa energiaa. Jos tuotantoaikana käytetty energia myös korvataan uusiutuvalla energialla, niin GWP-arvo koko elinkaaren aikana laskee arvoon 1006 kg CO2eqv., mikä on vain 0,13 % saaduista tuloksista. Suurin osa tästä arvosta liittyy sekoittimen materiaalin, tässä tapauksessa ruostumattoman teräksen tuotantoon.