Browsing by Subject "EFFICIENT"

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  • Lagerspets, Emi; Valbonetti, Evelyn; Eronen, Aleksi; Repo, Timo (2021)
    We report here novel Cu(I) thiophene carbaldimine catalysts for the selective aerobic oxidation of primary alcohols to their corresponding aldehydes and various diols to lactones or lactols. In the presence of the in situ generated Cu(I) species, a persistent radical (2,2,6,6-tetramethylpiperdine-N-oxyl (TEMPO)) and N-methylimidazole (NMI) as an auxiliary ligand, the reaction proceeds under aerobic conditions and at ambient temperature. Especially the catalytic system of 1-(thiophen-2-yl)-N-(4-(trifluoromethoxy)phenyl)methanimine (ligand L2) with copper(I)-iodide showed high reactivity for all kind of alcohols (benzylic, allylic and aliphatic). In the case of benzyl alcohol even 2.5 mol% of copper loading gave quantitative yield. Beside high activity under aerobic conditions, the catalysts ability to oxidize 1,5-pentadiol to the corresponding lactol (86% in 4 h) and Nphenyldiethanolamine to the corresponding morpholine derivate lactol (86% in 24 h) is particularly noteworthy.
  • Bahadori, Milad; Jarvinen, Kimmo (2020)
    A multitude of privacy-enhancing technologies (PETs) has been presented recently to solve the privacy problems of contemporary services utilizing cloud computing. Many of them are based on additively homomorphic encryption (AHE) that allows the computation of additions on encrypted data. The main technical obstacles for adaptation of PETs in practical systems are related to performance overheads compared with current privacy-violating alternatives. In this article, we present a hardware/software (HW/SW) codesign for programmable systems-on-chip (SoCs) that is designed for accelerating applications based on the Paillier encryption. Our implementation is a microcode-based multicore architecture that is suitable for accelerating various PETs using AHE with large integer modular arithmetic. We instantiate the implementation in a Xilinx Zynq-7000 programmable SoC and provide performance evaluations in real hardware. We also investigate its efficiency in a high-end Xilinx UltraScale+ programmable SoC. We evaluate the implementation with two target use cases that have relevance in PETs: privacy-preserving computation of squared Euclidean distances over encrypted data and multi-input functional encryption (FE) for inner products. Both of them represent the first hardware acceleration results for such operations, and in particular, the latter one is among the very first published implementation results of FE on any platform.
  • Wannasarit, Saowanee; Wang, Shiqi; Figueiredo, Patricia; Trujillo Olvera, Claudia Ximenia; Eburnea, Francesca; Simón-Gracia, Lorena; Correia, Alexandra; Ding, Yaping; Teesalu, Tambet; Liu, Dongfei; Wiwattanapatapee, Ruedeekorn; Santos, Hélder A.; Li, Wei (2019)
    Achieving cellular internalization and endosomal escape remains a major challenge for many antitumor therapeutics, especially macromolecular drugs. Viral drug carriers are reported for efficient intracellular delivery, but with limited choices of payloads. In this study, a novel polymeric nanoparticle (ADMAP) is developed, resembling the structure and functional features of a virus. ADMAP is synthesized by grafting endosomolytic poly(lauryl methacrylate‐co‐methacrylic acid) on acetalated dextran. The endosomolytic polymer mimics the capsid protein for endosomal escape, and acetalated dextran resembles the viral core for accommodating payloads. After polymer synthesis, the subsequent controlled nanoprecipitation on a microfluidic device yields uniform nanoparticles with high encapsulation efficiency. At late endosomal pH (5.0), the ADMAP particles successfully destabilize endosomal membranes and release the drug payloads synergistically, resulting in a greater therapeutic efficacy compared with that of free anticancer drugs. Further conjugation of a tumor‐penetrating peptide enhances the antitumor efficacy toward 3D spheroids and finally leads to spheroid disintegration. The unique structure along with the synergistic endosomal escape and drug release make ADMAP nanoparticles favorable for intracellular delivery of antitumor therapeutics.
  • Fraser, James P.; Postnikov, Pavel; Miliutina, Elena; Kolska, Zdenka; Valiev, Rashid; Svorcik, Vaclav; Lyutakov, Oleksiy; Ganin, Alexey Y.; Guselnikova, Olga (2020)
    Two-dimensional (2D) transition-metal dichalcogenides have become promising candidates for surface-enhanced Raman spectroscopy (SERS), but currently very few examples of detection of relevant molecules are available. Herein, we show the detection of the lipophilic disease marker beta-sitosterol on few-layered MoTe2 films. The chemical vapor deposition (CVD)-grown films are capable of nanomolar detection, exceeding the performance of alternative noble-metal surfaces. We confirm that the enhancement occurs through the chemical enhancement (CE) mechanism via formation of a surface-analyte complex, which leads to an enhancement factor of approximate to 10(4), as confirmed by Fourier transform infrared (FTIR), UV-vis, and cyclic voltammetry (CV) analyses and density functional theory (DFT) calculations. Low values of signal deviation over a seven-layered MoTe2 film confirms the homogeneity and reproducibility of the results in comparison to noble-metal substrate analogues. Furthermore, beta-sitosterol detection within cell culture media, a minimal loss of signal over 50 days, and the opportunity for sensor regeneration suggest that MoTe2 can become a promising new SERS platform for biosensing.
  • Popov, Georgi; Bačić, Goran; Mattinen, Miika; Manner, Toni; Lindström, Hannu; Seppänen, Heli; Suihkonen, Sami; Vehkamäki, Marko; Kemell, Marianna; Jalkanen, Pasi; Mizohata, Kenichiro; Räisänen, Jyrki; Leskelä, Markku; Koivula, Hanna Maarit; Barry, Seán T.; Ritala, Mikko (2020)
    Atomic layer deposition (ALD) is a viable method for depositing functional, passivating, and encapsulating layers on top of halide perovskites. Studies in that area have only focused on metal oxides, despite a great number of materials that can be made with ALD. This work demonstrates that, in addition to oxides, other ALD processes can be compatible with the perovskites. We describe two new ALD processes for lead sulfide. These processes operate at low deposition temperatures (45-155 degrees C) that have been inaccessible to previous ALD PbS processes. Our processes rely on volatile and reactive lead precursors Pb(dbda) (dbda = rac-N-2,N-3-di-tertbutylbutane-2,3-diamide) and Pb(btsa)(2) (btsa = bis(trimethylsilyl)amide) as well as H2S. These precursors produce high quality PbS thin films that are uniform, crystalline, and pure. The films exhibit p- type conductivity and good mobilities of 10-70 cm(2) V-1 s(-1). Low deposition temperatures enable direct ALD of PbS onto a halide perovskite CH3NH3PbI3 (MAPI) without its decomposition. The stability of MAPI in ambient air is greatly improved by capping with ALD PbS. More generally, these new processes offer valuable alternatives for PbS-based devices, and we hope that this study will inspire more studies on ALD of non-oxides on halide perovskites.
  • Yang, Dong; Tenhu, Heikki; Hietala, Sami (2020)
    In both chemo- and biocatalysis the immobilization of catalysts to carriers is often beneficial in terms of catalytic activity and ease of operation. In the present study we encapsulated an enzyme, beta-D-glucosidase, inside thermosensitive poly(N-acryloyl glycinamide) microgels by radical polymerization of N-acryloyl glycinamide in the presence of the enzymes. Properties of these hybrid microgels were studied varying the enzyme-monomer ratio and the degree of crosslinking. The enzymatic activities of the microgels were assessed using a model reaction, enzymatic cleavage of p-nitrophenyl-beta-D-glucopyranoside under different conditions. The microgel encapsulated enzymes showed enhanced activity at high pH compared to the native enzymes. Once the enzymatic activity of the microgels was ascertained, introduction of silver nanoparticles inside the enzyme carrying microgels was made to develop bicatalytic systems. The bicatalytic microgels were shown to be capable of carrying out a cascade reaction combining enzymatic catalysis and reduction of the reaction product 4-nitrophenol to 4-aminophenol.
  • Makela, Mikko K.; Bulatov, Evgeny; Malinen, Kiia; Talvitie, Juulia; Nieger, Martin; Melchionna, Michele; Lenarda, Anna; Hu, Tao; Wirtanen, Tom; Helaja, Juho (2021)
    Oxidized active carbon (oAC) catalyses the formation of polysubstituted quinolines from o-vinyl anilines and aldehydes. The reaction proceeds in a cascade manner through condensation, electrocyclization and dehydrogenation, and gives access to a wide range of quinolines with alkyl and/or aryl substituents as demonstrated with 40 examples. The metal-free catalytic procedure allows a heterogeneous protocol for the synthesis of various polysubstituted quinolines. The mechanistic studies imply that both the acid and quinoidic groups in oAC are integral for the catalytic manifold.
  • Al-Hunaiti, Afnan; Abu-Radaha, Batool; Wraith, Darren; Repo, Timo (2022)
    Here, we disclose a new copper(i)-Schiff base complex series for selective oxidation of primary alcohols to aldehydes under benign conditions. The catalytic protocol involves 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), N-methylimidazole (NMI), ambient air, acetonitrile, and room temperature. This system provides a straightforward and rapid pathway to a series of Schiff bases, particularly, the copper(i) complexes bearing the substituted (furan-2-yl)imine bases N-(4-fluorophenyl)-1-(furan-2-yl)methanimine (L2) and N-(2-fluoro-4-nitrophenyl)-1-(furan-2-yl)methanimine (L4) have shown excellent yields. Both benzylic and aliphatic alcohols were converted to aldehydes selectively with 99% yield (in 1-2 h) and 96% yield (in 16 h). The mechanistic studies via kinetic analysis of all components demonstrate that the ligand type plays a key role in reaction rate. The basicity of the ligand increases the electron density of the metal center, which leads to higher oxidation reactivity. The Hammett plot shows that the key step does not involve H-abstraction. Additionally, a generalized additive model (GAM, including random effect) showed that it was possible to correlate reaction composition with catalytic activity, ligand structure, and substrate behavior. This can be developed in the form of a predictive model bearing in mind numerous reactions to be performed or in order to produce a massive data-set of this type of oxidation reaction. The predictive model will act as a useful tool towards understanding the key steps in catalytic oxidation through dimensional optimization while reducing the screening of statistically poor active catalysis.
  • Sandholm, Niina; Haukka, Jani K.; Toppila, Iiro; Valo, Erkka; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik (2018)
    Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value <5 x 10(-8)) with diabetic albuminuria, in Finnish individuals with type 1 diabetes; However, replication attempt in non-Finnish Europeans with type 1 diabetes showed nominally significant association in the opposite direction, suggesting a population-specific effect, but simultaneously leaving the finding controversial. In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association. The association was particularly pronounced in subjects not reaching the treatment target for blood glucose levels (HbA(1c) > 7%; N = 2560, p = 1.7 x 10(-9)). Even though further studies are needed to pinpoint the causal variants, dissecting the association at the GLRA3 locus may uncover novel molecular mechanisms for diabetic albuminuria irrespective of population background.
  • Savelainen, Matti; Väliviita, Jussi; Walia, Parampreet; Rusak, Stanislav; Kurki-Suonio, Hannu (2013)
  • Ma, Hao; Zhou, Bo; Li, Yiqun; Argyropoulos, Dimitris S. (2012)
  • Beyer, Hannes M.; Mikula, Kornelia M.; Kudling, Tatiana V.; Iwaï, Hideo (2019)
    Self-splicing inteins are mobile genetic elements invading host genes via nested homing endonuclease (HEN) domains. All HEN domains residing within inteins are inserted at a highly conserved insertion site. A purifying selection mechanism directing the location of the HEN insertion site has not yet been identified. In this work, we solved the three-dimensional crystal structures of two inteins inserted in the cell division control protein 21 of the hyperthermophilic archaea Pyrococcus abyssi and Pyrococcus horikoshii. A comparison between the structures provides the structural basis for the thermo-stabilization mechanism of inteins that have lost the HEN domain during evolution. The presence of an entire extein domain in the intein structure from Pyrococcus horikoshii suggests the selection mechanism for the highly conserved HEN insertion point.
  • NHLBI TOPMED Lipids Working Grp (2018)
    Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation(similar to 30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.
  • Parkkinen, Pauli; Xu, Wen-Hua; Solala, Eelis; Sundholm, Dage (2018)
    Density functional theory within the Kohn-Sham density functional theory (KS-DFT) ansatz has been implemented into our bubbles and cube real-space molecular electronic structure framework, where functions containing steep cusps in the vicinity of the nuclei are expanded in atom-centered one-dimensional (1D) numerical grids multiplied with spherical harmonics (bubbles). The remainder, i.e., the cube, which is the cusp-free and smooth difference between the atomic one-center contributions and the exact molecular function, is represented on a three-dimensional (3D) equidistant grid by using a tractable number of grid points. The implementation of the methods is demonstrated by performing 3D numerical KS-DFT calculations on light atoms and small molecules. The accuracy is assessed by comparing the obtained energies with the best available reference energies.
  • LifeLines Cohort Study; DiscovEHR MyCode Study; VA Million Vet Program; LifeLines Cohort Study; DiscovEHR MyCode Study; VA Million Vet Program; Winkler, Thomas W.; Rasheed, Humaira; Teumer, Alexander; Perola, Markus; Salomaa, Veikko; Kuokkanen, Mikko (2022)
    A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease. Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n(DM) = 178,691, n(noDM) = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
  • Stahlberger, Mareen; Schwarz, Noah; Zippel, Christoph; Hohmann, Jens; Nieger, Martin; Hassan, Zahid; Brase, Stefan (2022)
    This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienayme three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation.
  • Vauhkonen, Jari (2020)
    Key Message Tree-level forest inventory data are becoming increasingly available, which motivates the use of these data for decision-making. However, airborne inventories carried out tree-by-tree typically include systematic errors, which can propagate to objective function variables used to determine optimal forest management. Effects of under-detection focused on the smallest trees on predicted immediate harvest profits and future expectation values were assessed assuming different sites and interest rates. Management decisions based on the erroneous information caused losses of 0-17% of the total immediate and future expected income of Scots pine stands. Context Optimal decisions on how to manage forest stands can depend on the absence or presence of intermediate and understory trees. Yet, these tree strata are likely prone to inventory errors. Aims The aim of this study is to examine implications of making stand management decisions based on data that include systematic errors resembling those typically observed in airborne inventories carried out tree-by-tree. Methods Stand management instructions were developed based on theoretical diameter distribution functions simulated to have different shape, scale, and frequency parameters corresponding to various degrees of under-detection focused on the smallest trees. Immediate harvest income and future expectation value were derived based on various management alternatives simulated. Results Errors in diameter distributions affected the predicted harvest profits and future expectation values differently between the simulated alternatives and depending on site type and interest rate assumptions. As a result, different alternatives were considered as optimal management compared to the use of the error-free reference distributions. In particular, the use of no management or most intensive management alternatives became preferred over alternatives with intermediate harvesting intensities. Certain harvesting types such as thinning from below became preferred more often than what was optimal. The errors did not affect the selection of the management alternative in 71% of the simulations, whereas in the remaining proportion, relying on the erroneous information would have caused losing 2%, on average, and 17% at maximum, of the total immediate and future expected income. Conclusion The effects above might not have been discovered, if the results were validated for inventory totals instead of separately considering the immediate and future income and losses produced by the erroneous decisions. It is recommended not to separate but to integrate the inventory and planning systems for well-informed decisions.
  • Isokuortti, Jussi; Kuntze, Kim; Virkki, Matti; Ahmed, Zafar; Vuorimaa-Laukkanen, Elina; Filatov, Mikhail A.; Turshatov, Andrey; Laaksonen, Timo; Priimagi, Arri; Durandin, Nikita A. (2021)
    Developing azobenzene photoswitches capable of selective and efficient photoisomerization by long-wavelength excitation is an enduring challenge. Herein, rapid isomerization from the Z- to E-state of two ortho-functionalized bistable azobenzenes with near-unity photoconversion efficiency was driven by triplet energy transfer upon red and near-infrared (up to 770 nm) excitation of porphyrin photosensitizers in catalytic micromolar concentrations. We show that the process of triplet-sensitized isomerization is efficient even when the sensitizer triplet energy is substantially lower (>200 meV) than that of the azobenzene used. This makes the approach applicable for a wide variety of sensitizer-azobenzene combinations and enables the expansion of excitation wavelengths into the near-infrared spectral range. Therefore, indirect excitation via endothermic triplet energy transfer provides efficient and precise means for photoswitching upon 770 nm near-infared light illumination with no chemical modification of the azobenzene chromophore, a desirable feature in photocontrollable biomaterials.
  • Gilman, Ekaterina; Tamminen, Satu; Keskinarkaus, Anja; Anagnostopoulos, Theodoros; Su, Xiang; Pirttikangas, Susanna; Riekki, Jukka (IEEE Computer Society, 2020)
    IEEE International Conference on Data Engineering Workshop
    Advances in technology equip traffic domain with instruments to gather and analyse data for safe and fuel-efficient traveling. In this article, we elaborate on the effects that taxi drivers' route selection has on fuel efficiency. For this purpose, we fuse real driving behaviour data from taxi cabs, weather, digital map, and traffic situation information to gain understanding of how the routes are selected and what are the effects in terms of fuel-efficiency. Analysis of actually driven trips and their quickest and shortest counterparts is conducted to find out the fuel-efficiency consequences on route selection. The judgments are used for developing a fuel-consumption model, exploring further the route characteristics and external factors affecting fuel consumption.
  • FinnGen; Leskelä, Jaakko; Toppila, Iiro; Härmä, Mari-Anne; Palviainen, Teemu; Salminen, Aino; Sandholm, Niina; Pietiäinen, Milla; Kopra, Elisa; Pais de Barros, Jean-Paul; Lassenius, Mariann I.; Kumar, Anmol; Harjutsalo, Valma; Roslund, Kajsa; Forsblom, Carol; Loukola, Anu; Havulinna, Aki S.; Lagrost, Laurent; Salomaa, Veikko; Groop, Per-Henrik; Perola, Markus; Kaprio, Jaakko; Lehto, Markku; Pussinen, Pirkko J. (2021)
    Background Translocation of lipopolysaccharide from gram-negative bacteria into the systemic circulation results in endotoxemia. In addition to acute infections, endotoxemia is detected in cardiometabolic disorders, such as cardiovascular diseases and obesity. Methods and Results We performed a genome-wide association study of serum lipopolysaccharide activity in 11 296 individuals from 6 different Finnish study cohorts. Endotoxemia was measured by limulus amebocyte lysate assay in the whole population and by 2 other techniques (Endolisa and high-performance liquid chromatography/tandem mass spectrometry) in subpopulations. The associations of the composed genetic risk score of endotoxemia and thrombosis-related clinical end points for 195 170 participants were analyzed in FinnGen. Lipopolysaccharide activity had a genome-wide significant association with 741 single-nucleotide polymorphisms in 5 independent loci, which were mainly located at genes affecting the contact activation of the coagulation cascade and lipoprotein metabolism and explained 1.5% to 9.2% of the variability in lipopolysaccharide activity levels. The closest genes included KNG1, KLKB1, F12, SLC34A1, YPEL4, CLP1, ZDHHC5, SERPING1, CBX5, and LIPC. The genetic risk score of endotoxemia was associated with deep vein thrombosis, pulmonary embolism, pulmonary heart disease, and venous thromboembolism. Conclusions The biological activity of lipopolysaccharide in the circulation (ie, endotoxemia) has a small but highly significant genetic component. Endotoxemia is associated with genetic variation in the contact activation pathway, vasoactivity, and lipoprotein metabolism, which play important roles in host defense, lipopolysaccharide neutralization, and thrombosis, and thereby thromboembolism and stroke.