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.
  • 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.
  • 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.
  • LifeLines Cohort Study (2018)
    Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
  • Tanskanen, Tomas; van den Berg, Linda; Valimaki, Niko; Aavikko, Mervi; Ness-Jensen, Eivind; Hveem, Kristian; Wettergren, Yvonne; Lindskog, Elinor Bexe; Tonisson, Neeme; Metspalu, Andres; Silander, Kaisa; Orlando, Giulia; Law, Philip J.; Tuupanen, Sari; Gylfe, Alexandra E.; Hanninen, Ulrika A.; Cajuso, Tatiana; Kondelin, Johanna; Sarin, Antti-Pekka; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Jarvinen, Heikki; Renkonen-Sinisalo, Laura; Lepisto, Anna; Bohm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan M.; Timofeeva, Maria N.; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Tim S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Win, Aung K.; Hopper, John; Jenkins, Mark A.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fredrick R.; Casey, Graham; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P.; Houlston, Richard S.; Palin, Kimmo; Aaltonen, Lauri A. (2018)
    Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate
  • Hebbar, Prashantha; Abu-Farha, Mohamed; Alkayal, Fadi; Nizam, Rasheeba; Elkum, Naser; Melhem, Motasem; John, Sumi Elsa; Channanath, Arshad; Abubaker, Jehad; Bennakhi, Abdullah; Al-Ozairi, Ebaa; Tuomilehto, Jaakko; Pitkäniemi, Janne; Alsmadi, Osama; Al-Mulla, Fahd; Thanaraj, Thangavel Alphonse (2020)
    Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 (RPS6KA1) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; beta-discovery = 8.315; beta-replication = 3.442; beta-combined = 6.551). Further, three suggestive associations (p-values <8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.
  • Hällfors, Jenni; Palviainen, Teemu; Surakka, Ida; Gupta, Richa; Buchwald, Jadwiga; Raevuori, Anu; Ripatti, Samuli; Korhonen, Tellervo; Jousilahti, Pekka; Madden, Pamela A. F.; Kaprio, Jaakko; Loukola, Anu (2019)
    The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome-wide association study on 1715 ever smokers ascertained from the population-based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence-based Finnish reference panel. We analyzed three measures of nicotine addiction-smoking quantity, nicotine dependence and nicotine withdrawal. We annotated all genome-wide significant SNPs for their functional potential. First, we detected genome-wide significant association on 16p12 with smoking quantity (P = 8.5 x 10(-9)), near CLEC19A. The lead-SNP stands 22 kb from a binding site for NF-kappa B transcription factors, which play a role in the neurotrophin signaling pathway. However, the signal was not replicated in an independent Finnish population-based sample, FINRISK (n = 6763). Second, nicotine withdrawal showed association on 2q21 in an intron of TMEM163 (P = 2.1 x 10(-9)), and on 11p15 (P = 6.6 x 10(-8)) in an intron of AP2A2, and P = 4.2 x 10(-7) for a missense variant in MUC6, both involved in the neurotrophin signaling pathway). Third, association was detected on 3p22.3 for maximum number of cigarettes smoked per day (P = 3.1 x 10(-8)) near STAC. Associating CLEC19A and TMEM163 SNPs were annotated to influence gene expression or methylation. The neurotrophin signaling pathway has previously been associated with smoking behavior. Our findings further support the role in nicotine addiction.