Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

Platinum (II) and palladium (II) complexes with (N,N') and (C,N,N') ligands derived from pyrazole as anticancer and antimalarial agents: synthesis, characterization and in vitro activities

The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH2)2NMe2}-3,5-R2-pzol] {where pzol represents pyrazole and Rdouble bond; length as m-dashH (1a), Me (1b) or Ph (1c)} with [MCl2(DMSO)2] (Mdouble bond; length as m-dashPt or Pd) under different experimental conditions allowed us to isolate and characterize cis-[M{κ2-N,N′-{[1-(CH2)2NMe2}-3,5-R2-pzol])}Cl2] {MMdouble bond; length as m-dashPtPt (2a-2c) or Pd (3a-3c)} and two cyclometallated complexes [M{κ3-C,N,N′-{[1-(CH2)2NMe2}-3-(C5H4)-5-Ph-pzol])}Cl] {Mdouble bond; length as m-dashPt(II) (4c) or Pd(II) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC50 = 3 μM) versus breast cancer cell lines (IC50 > 20 μM). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

Environmental Monitoring using Image Analysis

Tärkeä tehtävä ympäristön tarkkailussa on arvioida ympäristön nykyinen tila ja ihmisen siihen aiheuttamat muutokset sekä analysoida ja etsiä näiden yhtenäiset suhteet. Ympäristön muuttumista voidaan hallita keräämällä ja analysoimalla tietoa. Tässä diplomityössä on tutkittu vesikasvillisuudessa hai vainuja muutoksia käyttäen etäältä hankittua mittausdataa ja kuvan analysointimenetelmiä. Ympäristön tarkkailuun on käytetty Suomen suurimmasta järvestä Saimaasta vuosina 1996 ja 1999 otettuja ilmakuvia. Ensimmäinen kuva-analyysin vaihe on geometrinen korjaus, jonka tarkoituksena on kohdistaa ja suhteuttaa otetut kuvat samaan koordinaattijärjestelmään. Toinen vaihe on kohdistaa vastaavat paikalliset alueet ja tunnistaa kasvillisuuden muuttuminen. Kasvillisuuden tunnistamiseen on käytetty erilaisia lähestymistapoja sisältäen valvottuja ja valvomattomia tunnistustapoja. Tutkimuksessa käytettiin aitoa, kohinoista mittausdataa, minkä perusteella tehdyt kokeet antoivat hyviä tuloksia tutkimuksen onnistumisesta.

Orthogonal protecting groups in the synthesis of tryptophanyl-hexahydropyrroloindoles

The synthesis of various polycyclic systems containing a C3a-Ni bond between a hexahydropyrrolo[2,3-b]indole and an indole tryptophan is described here. A series of experiments were performed to determine the best combination of five orthogonal protecting groups and the best reaction conditions for formation of said bond, which is a common feature among many recently discovered marine natural products.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

Corporate Identity and Desired Image Elements as a Basis for Corporate Image Development, Case: Myllykoski Sales

Tutkimuksen päätavoitteena oli auttaa Myllykoski –ryhmää määrittämään, mistä tekijöistä ryhmän uuden myyntiorganisaation, Myllykoski Salesin, tulevaisuuden imagon tulisi koostua. Näin ollen tutkimus pyrki selvittämään Myllykoski –ryhmän yritysidentiteetin nykytilaa ja Myllykoski Salesin toivottuja imagotekijöitä, sekä vertaamaan niiden vastaavuutta. Lisäksi tutkimuksen tavoitteena oli tutkia Myllykoski –ryhmän nykyistä ja toivottua tulevaisuuden imagotilaa. Jotta imagonrakennusprosessi olisi menestyksekäs, rakennettavan imagon ja viestittävien imagotekijöiden tulisi perustua yritysidentiteetin todellisiin tekijöihin. Yritysidentiteetin voidaan määritellä olevan yhtäläinen sisäisten sidosryhmien muodostaman yritysmielikuvan kanssa ja näin ollen nykyinen yritysidentiteetti voidaan paljastaa tutkimalla henkilökunnan mielipiteitä työorganisaatiotaan kohtaan. Näin ollen käsiteltävä tutkimus suoritettiin tekemällä kaksi sähköpostikyselyä, jotka suunnattiin Myllykoski -ryhmän myynti- ja markkinointihenkilökunnalle. Tutkimusten vastausprosentit olivat 71,4 % (johto, 14 lähetettyä kyselyä) ja 51,9 % (muu henkilökunta, 108 lähetettyä kyselyä). Saatuja vastauksia analysoitiin sekä laadullisesti että määrällisesti. Saaduista vastauksista oli selvästi havaittavissa Myllykoski –ryhmän yritysidentiteetin nykytila, nykyinen ja toivottu imagotila, sekä Myllykoski Salesin toivotut imagotekijät. Verrattaessa toivottuja imagotekijöitä ryhmän yritysidentiteettiin havaittiin, että suurin osa halutuista imagotekijöistä vastasi ryhmän identiteetin nykytilan ominaisuuksia ja näin ollen kyseisiä tekijöitä voitaisiin huoletta viestiä rakennettaessa Myllykoski Salesin imagoa. Joidenkin toivottujen imagotekijöiden viestintää tulisi kuitenkin vakavasti harkita, jottei rakennettaisi epärealistista imagoa.

Value and Prices in Russian Economic Thought: A journey inside the Russian Synthesis, 1890-1920

This book explores Russian synthesis that occurred in Russian economic thought between 1890 and 1920. This includes all the attempts at synthesis between classical political economy and marginalism; the labour theory of value and marginal utility; and value and prices. The various ways in which Russian economists have approached these issues have generally been addressed in a piecemeal fashion in history of economic thought literature. This book returns to the primary sources in the Russian language, translating many into English for the first time, and offers the first comprehensive history of the Russian synthesis. The book first examines the origins of the Russian synthesis by determining the condition of reception in Russia of the various theories of value involved: the classical theories of value of Ricardo and Marx on one side; the marginalist theories of prices of Menger, Walras and Jevons on the other. It then reconstructs the three generations of the Russian synthesis: the first (Tugan-Baranovsky), the second, the mathematicians (Dmitriev, Bortkiewicz, Shaposhnikov, Slutsky, etc.) and the last (Yurovsky), with an emphasis on Tugan-Baranovsky's initial impetus. This volume is suitable for those studying economic theory and philosophy as well as those interested in the history of economic thought.

Image Resilience after Multiple Crises : The Case of Switzerland in the United States

In der heutigen Welt sind die Reputation und das Image eines Landes als wichtige Faktoren für den wirtschaftlichen und politischen Erfolg angesehen. Jedoch ist die Pflege der Marke eines Landes komplex und führt zu zwei Positionen, die sich potentiell widersprechen: Einerseits kann ein positives Erscheinungsbild eines Landes durch aktive Massnahmen gefördert werden. Andererseits ist es schwierig, das Bild eines Landes abzugrenzen und es ist mit Klischees behaftet. Dieser Beitrag analysiert die Auswirkungen von zwei grösseren Krisen auf das Image der Schweiz in den Vereinigten Staaten: die Krise um die nachrichtenlosen Vermögen aus der Zeit des 2. Weltkriegs im Jahr 2000 sowie die Krise um die UBS und das Bankgeheimnis im Jahr 2009. Die Studie zeigt, dass das Erscheinungsbild der Schweiz unberührt blieb, obwohl ein beachtlicher Teil der Bevölkerung und der Meinungsführer von beiden Krisen wusste. Dies stützt die Hypothese, dass das Image eines Landes eine hohe Beständigkeit aufweist. In today's world, country's reputation and image have become key issues, widely believed to be success factors both economically and politically. Nevertheless, managing a country's brand is complex and leads to two positions that are potentially contradictory: On the one hand, a country's image can be influenced either by promotional activities. On the other hand, a country's image is a construct that is very difficult to delimit and is highly stereotyped. This contribution study the impact of two major crises on the image of Switzerland in the United States: the unclaimed wartime deposits crisis in 2000 and the UBS and banking secrecy crisis in 2009. It shows that despite the fact that a substantial proportion of the public and of opinion leaders was aware of both crises, the image of Switzerland was unaffected, which tends to support the hypothesis of strong stability of a country's image.

Statistical Analysis of Spectral Images

Tämä diplomityö liittyy Spektrikuvien tutkimiseen tilastollisen kuvamallin näkökulmasta. Diplomityön ensimmäisessä osassa tarkastellaan tilastollisten parametrien jakaumien vaikutusta väreihin ja korostumiin erilaisissa valaistusolosuhteissa. Havaittiin, että tilastollisten parametrien väliset suhteet eivät riipu valaistusolosuhteista, mutta riippuvat kuvan häiriöttömyydestä. Ilmeni myös, että korkea huipukkuus saattaa aiheutua värikylläisyydestä. Lisäksi työssä kehitettiin tilastolliseen spektrimalliin perustuvaa tekstuurinyhdistämisalgoritmia. Sillä saavutettiin hyviä tuloksia, kun tilastollisten parametrien väliset riippuvuussuhteet olivat voimassa. Työn toisessa osassa erilaisia spektrikuvia tutkittiin käyttäen itsenäistä komponenttien analyysia (ICA). Seuraavia itsenäiseen komponenttien analyysiin tarkoitettuja algoritmia tarkasteltiin: JADE, kiinteän pisteen ICA ja momenttikeskeinen ICA. Tutkimuksissa painotettiin erottelun laatua. Paras erottelu saavutettiin JADE- algoritmilla, joskin erot muiden algoritmien välillä eivät olleet merkittäviä. Algoritmi jakoi kuvan kahteen itsenäiseen, joko korostuneeseen ja korostumattomaan tai kromaattiseen ja akromaattiseen, komponenttiin. Lopuksi pohditaan huipukkuuden suhdetta kuvan ominaisuuksiin, kuten korostuneisuuteen ja värikylläisyyteen. Työn viimeisessä osassa ehdotetaan mahdollisia jatkotutkimuskohteita.

Highly efficient, multigram and enantiopure synthesis of (S)-2-(2,4′-bithiazol-2-yl)pyrrolidine

(S)-2-(4-Bromo-2,4"-bithiazole)-1-(tert-butoxycarbonyl)pyrrolidine ((S)-1) was obtained as a single enantiomer and in high yield by means of a two-step modified Hantzsch thiazole synthesis reaction when bromoketone 3 and thioamide (S)-4 were used. Further conversion of (S)-1 into trimethyltin derivative (S)-2 broadens the scope for further cross-coupling reactions.