Polymer Photovoltaic Cells: Enhanced Efficiencies via a Network of Internal Donor-Acceptor Heterojunctions

G. Yu, J. Gao, J. C. Hummelen, F. Wudl, A. J. Heeger

Institute for Polymers and Organic Solids, University of California at Santa Barbara, Santa Barbara, CA 93106-5090, USA.

Abstract: The carrier collection efficiency (η c ) and energy conversion efficiency (η e ) of polymer photovoltaic cells were improved by blending of the semiconducting polymer with C 60 or its functionalized derivatives. Composite films of poly(2-methoxy-5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene) (MEH-PPV) and fullerenes exhibit η c of about 29 percent of electrons per photon and η e of about 2.9 percent, efficiencies that are better by more than two orders of magnitude than those that have been achieved with devices made with pure MEH-PPV. The efficient charge separation results from photoinduced electron transfer from the MEH-PPV (as donor) to C 60 (as acceptor); the high collection efficiency results from a bicontinuous network of internal donor-acceptor heterojunctions.


Solar Water Splitting Cells

Michael G. Walter, Emily L. Warren, James R. McKone, Shannon W. Boettcher, Qixi Mi, Elizabeth A. Santori, Nathan S. Lewis

Division of Chemistry and Chemical Engineering, 210 Noyes Laboratory, 127-72 California Institute of Technology, Pasadena, California 91125


Abundances of the elements: Meteoritic and solar


The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine


A simple technique for quantitation of low levels of DNA damage in individual cells

Narendra P. Singh, Michael T. McCoy, Raymond R. Tice, Edward L. Schneider


Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

American Association for the Advancement of Science (AAAS)

Junying Yu, Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L. Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, James A. Thomson

Genome Center of Wisconsin, Madison, WI 53706–1580, USA.

Abstract: Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors ( OCT4, SOX2, NANOG , and LIN28 ) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.


A novel potent vasoconstrictor peptide produced by vascular endothelial cells

Masashi Yanagisawa, Hiroki Kurihara, Sadao Kimura, Yoko Tomobe, Mieko Kobayashi, Youji Mitsui, Yoshio Yazaki, Katsutoshi Goto, Tomoh Masaki


Dye-Sensitized Solar Cells

Anders Hagfeldt, Gerrit Boschloo, Licheng Sun, Lars Kloo, Henrik Pettersson

Department of Physical and Analytical Chemistry, Uppsala University, Box 259, SE-751 05 Uppsala, Sweden, Department of Chemistry, KTH - Royal Institute of Technology, Teknikringen 30, SE-100 44 Stockholm, Sweden, State Key Laboratory of Fine Chemicals, DUT-KTH Joint Education and Research Centre on Molecular Devices, Dalian University of Technology (DUT), Dalian 116012, China, and Swerea IVF AB, Box 104, SE-431 22 Mölndal, Sweden


Prospective identification of tumorigenic breast cancer cells

Proceedings of the National Academy of Sciences

Muhammad Al-Hajj, Max S. Wicha, Adalberto Benito-Hernandez, Sean J. Morrison, Michael F. Clarke

Departments of Internal Medicine and Pathology, Comprehensive Cancer Center, Department of Developmental Biology, and Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109

Abstract: Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD44 + CD24 −/low Lineage − in eight of nine patients. As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. The tumorigenic subpopulation could be serially passaged: each time cells within this population generated new tumors containing additional CD44 + CD24 −/low Lineage − tumorigenic cells as well as the phenotypically diverse mixed populations of nontumorigenic cells present in the initial tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies.


Powering the planet: Chemical challenges in solar energy utilization

*Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125; and

Abstract: Global energy consumption is projected to increase, even in the face of substantial declines in energy intensity, at least 2-fold by midcentury relative to the present because of population and economic growth. This demand could be met, in principle, from fossil energy resources, particularly coal. However, the cumulative nature of CO 2 emissions in the atmosphere demands that holding atmospheric CO 2 levels to even twice their preanthropogenic values by midcentury will require invention, development, and deployment of schemes for carbon-neutral energy production on a scale commensurate with, or larger than, the entire present-day energy supply from all sources combined. Among renewable energy resources, solar energy is by far the largest exploitable resource, providing more energy in 1 hour to the earth than all of the energy consumed by humans in an entire year. In view of the intermittency of insolation, if solar energy is to be a major primary energy source, it must be stored and dispatched on demand to the end user. An especially attractive approach is to store solar-converted energy in the form of chemical bonds, i.e., in a photosynthetic process at a year-round average efficiency significantly higher than current plants or algae, to reduce land-area requirements. Scientific challenges involved with this process include schemes to capture and convert solar energy and then store the energy in the form of chemical bonds, producing oxygen from water and a reduced fuel such as hydrogen, methane, methanol, or other hydrocarbon species.


Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells

Sayda M. Elbashir, Jens Harborth, Winfried Lendeckel, Abdullah Yalcin, Klaus Weber, Thomas Tuschl


Stem cells, cancer, and cancer stem cells

Tannishtha Reya, Sean J. Morrison, Michael F. Clarke, Irving L. Weissman


Efficient planar heterojunction perovskite solar cells by vapour deposition

Mingzhen Liu, Michael B. Johnston, Henry J. Snaith


Lead Iodide Perovskite Sensitized All-Solid-State Submicron Thin Film Mesoscopic Solar Cell with Efficiency Exceeding 9%

Hui-Seon Kim, Chang-Ryul Lee, Jeong-Hyeok Im, Ki-Beom Lee, Thomas Moehl, Arianna Marchioro, Soo-Jin Moon, Robin Humphry-Baker, Jun-Ho Yum, Jacques E. Moser, Michael Grätzel, Nam-Gyu Park


Nutrient requirements of suspension cultures of soybean root cells


The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells

Sendurai A. Mani, Wenjun Guo, Mai-Jing Liao, Elinor Ng. Eaton, Ayyakkannu Ayyanan, Alicia Y. Zhou, Mary Brooks, Ferenc Reinhard, Cheng Cheng Zhang, Michail Shipitsin, Lauren L. Campbell, Kornelia Polyak, Cathrin Brisken, Jing Yang, Robert A. Weinberg


Massively parallel digital transcriptional profiling of single cells

Grace X. Y. Zheng, Jessica M. Terry, Phillip Belgrader, Paul Ryvkin, Zachary W. Bent, Ryan Wilson, Solongo B. Ziraldo, Tobias D. Wheeler, Geoff P. McDermott, Junjie Zhu, Mark T. Gregory, Joe Shuga, Luz Montesclaros, Jason G. Underwood, Donald A. Masquelier, Stefanie Y. Nishimura, Michael Schnall-Levin, Paul W. Wyatt, Christopher M. Hindson, Rajiv Bharadwaj, Alexander Wong, Kevin D. Ness, Lan W. Beppu, H. Joachim Deeg, Christopher McFarland, Keith R. Loeb, William J. Valente, Nolan G. Ericson, Emily A. Stevens, Jerald P. Radich, Tarjei S. Mikkelsen, Benjamin J. Hindson, Jason H. Bielas

Abstract: Abstract Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3′ mRNA counting of tens of thousands of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6 min, with ∼50% cell capture efficiency. To demonstrate the system’s technical performance, we collected transcriptome data from ∼250k single cells across 29 samples. We validated the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. We profiled 68k peripheral blood mononuclear cells to demonstrate the system’s ability to characterize large immune populations. Finally, we used sequence variation in the transcriptome data to determine host and donor chimerism at single-cell resolution from bone marrow mononuclear cells isolated from transplant patients.


Isolation of Putative Progenitor Endothelial Cells for Angiogenesis

Takayuki Asahara, Toyoaki Murohara, Alison Sullivan, Marcy Silver, Rien van der Zee, Tong Li, Bernhard Witzenbichler, Gina Schatteman, Jeffrey M. Isner

Departments of Medicine (Cardiology) and Biomedical Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, MA 02135, USA.

Abstract: Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression. In vitro, these cells differentiated into ECs. In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis. These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis.


The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells

Cole Trapnell, Davide Cacchiarelli, Jonna Grimsby, Prapti Pokharel, Shuqiang Li, Michael Morse, Niall J Lennon, Kenneth J Livak, Tarjei S Mikkelsen, John L Rinn


Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets

Evan Z. Macosko, Anindita Basu, Rahul Satija, James Nemesh, Karthik Shekhar, Melissa Goldman, Itay Tirosh, Allison R. Bialas, Nolan Kamitaki, Emily M. Martersteck, John J. Trombetta, David A. Weitz, Joshua R. Sanes, Alex K. Shalek, Aviv Regev, Steven A. McCarroll


The emergence of perovskite solar cells

Martin A. Green, Anita Ho-Baillie, Henry J. Snaith


Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics

X. Michalet, F. F. Pinaud, L. A. Bentolila, J. M. Tsay, S. Doose, J. J. Li, G. Sundaresan, A. M. Wu, S. S. Gambhir, S. Weiss

Department of Chemistry and Biochemistry, University of California, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA.

Abstract: Research on fluorescent semiconductor nanocrystals (also known as quantum dots or qdots) has evolved over the past two decades from electronic materials science to biological applications. We review current approaches to the synthesis, solubilization, and functionalization of qdots and their applications to cell and animal biology. Recent examples of their experimental use include the observation of diffusion of individual glycine receptors in living neurons and the identification of lymph nodes in live animals by near-infrared emission during surgery. The new generations of qdots have far-reaching potential for the study of intracellular processes at the single-molecule level, high-resolution cellular imaging, long-term in vivo observation of cell trafficking, tumor targeting, and diagnostics.


What Are Batteries, Fuel Cells, and Supercapacitors?

Institute for Chemistry and Technology of Inorganic Materials, Graz University of Technology, Stremayrgasse 16, A-8010 Graz, Austria


Observation of a new particle in the search for the Standard Model Higgs boson with the ATLAS detector at the LHC

G. Aad, T. Abajyan, B. Abbott, J. Abdallah, S. Abdel Khalek, A.A. Abdelalim, O. Abdinov, R. Aben, B. Abi, M. Abolins, O.S. AbouZeid, H. Abramowicz, H. Abreu, B.S. Acharya, L. Adamczyk, D.L. Adams, T.N. Addy, J. Adelman, S. Adomeit, P. Adragna, T. Adye, S. Aefsky, J.A. Aguilar-Saavedra, M. Agustoni, M. Aharrouche, S.P. Ahlen, F. Ahles, A. Ahmad, M. Ahsan, G. Aielli, T. Akdogan, T.P.A. Åkesson, G. Akimoto, A.V. Akimov, M.S. Alam, M.A. Alam, J. Albert, S. Albrand, M. Aleksa, I.N. Aleksandrov, F. Alessandria, C. Alexa, G. Alexander, G. Alexandre, T. Alexopoulos, M. Alhroob, M. Aliev, G. Alimonti, J. Alison, B.M.M. Allbrooke, P.P. Allport, S.E. Allwood-Spiers, J. Almond, A. Aloisio, R. Alon, A. Alonso, F. Alonso, A. Altheimer, B. Alvarez Gonzalez, M.G. Alviggi, K. Amako, C. Amelung, V.V. Ammosov, S.P. Amor Dos Santos, A. Amorim, N. Amram, C. Anastopoulos, L.S. Ancu, N. Andari, T. Andeen, C.F. Anders, G. Anders, K.J. Anderson, A. Andreazza, V. Andrei, M.-L. Andrieux, X.S. Anduaga, S. Angelidakis, P. Anger, A. Angerami, F. Anghinolfi, A. Anisenkov, N. Anjos, A. Annovi, A. Antonaki, M. Antonelli, A. Antonov, J. Antos, F. Anulli, M. Aoki, S. Aoun, L. Aperio Bella, R. Apolle, G. Arabidze, I. Aracena, Y. Arai, A.T.H. Arce, S. Arfaoui, J.-F. Arguin, E. Arik, M. Arik, A.J. Armbruster, O. Arnaez, V. Arnal, C. Arnault, A. Artamonov, G. Artoni, D. Arutinov, S. Asai, S. Ask, B. Åsman, L. Asquith, K. Assamagan, A. Astbury, M. Atkinson, B. Aubert, E. Auge, K. Augsten, M. Aurousseau, G. Avolio, R. Avramidou, D. Axen, G. Azuelos, Y. Azuma, M.A. Baak, G. Baccaglioni, C. Bacci, A.M. Bach, H. Bachacou, K. Bachas, M. Backes, M. Backhaus, J. Backus Mayes, E. Badescu, P. Bagnaia, S. Bahinipati, Y. Bai, D.C. Bailey, T. Bain, J.T. Baines, O.K. Baker, M.D. Baker, S. Baker, P. Balek, E. Banas, P. Banerjee, Sw. Banerjee, D. Banfi, A. Bangert, V. Bansal, H.S. Bansil, L. Barak, S.P. Baranov, A. Barbaro Galtieri, T. Barber, E.L. Barberio, D. Barberis, M. Barbero, D.Y. Bardin, T. Barillari, M. Barisonzi, T. Barklow, N. Barlow, B.M. Barnett, R.M. Barnett, A. Baroncelli, G. Barone, A.J. Barr, F. Barreiro, J. Barreiro Guimarães da Costa, P. Barrillon, R. Bartoldus, A.E. Barton, V. Bartsch, A. Basye, R.L. Bates, L. Batkova, J.R. Batley, A. Battaglia, M. Battistin, F. Bauer, H.S. Bawa, S. Beale, T. Beau, P.H. Beauchemin, R. Beccherle, P. Bechtle, H.P. Beck, A.K. Becker, S. Becker, M. Beckingham, K.H. Becks, A.J. Beddall, A. Beddall, S. Bedikian, V.A. Bednyakov, C.P. Bee, L.J. Beemster, M. Begel, S. Behar Harpaz, P.K. Behera, M. Beimforde, C. Belanger-Champagne, P.J. Bell, W.H. Bell, G. Bella, L. Bellagamba, M. Bellomo, A. Belloni, O. Beloborodova, K. Belotskiy, O. Beltramello, O. Benary, D. Benchekroun, K. Bendtz, N. Benekos, Y. Benhammou, E. Benhar Noccioli, J.A. Benitez Garcia, D.P. Benjamin, M. Benoit, J.R. Bensinger, K. Benslama, S. Bentvelsen, D. Berge, E. Bergeaas Kuutmann, N. Berger, F. Berghaus, E. Berglund, J. Beringer, P. Bernat, R. Bernhard, C. Bernius, F.U. Bernlochner, T. Berry, C. Bertella, A. Bertin, F. Bertolucci, M.I. Besana, G.J. Besjes, N. Besson, S. Bethke, W. Bhimji, R.M. Bianchi, M. Bianco, O. Biebel, S.P. Bieniek, K. Bierwagen, J. Biesiada, M. Biglietti, H. Bilokon, M. Bindi, S. Binet, A. Bingul, C. Bini, C. Biscarat, B. Bittner, K.M. Black, R.E. Blair, J.-B. Blanchard, G. Blanchot, T. Blazek, I. Bloch, C. Blocker, J. Blocki, A. Blondel, W. Blum, U. Blumenschein, G.J. Bobbink, V.B. Bobrovnikov, S.S. Bocchetta, A. Bocci, C.R. Boddy, M. Boehler, J. Boek, N. Boelaert, J.A. Bogaerts, A. Bogdanchikov, A. Bogouch, C. Bohm, J. Bohm, V. Boisvert, T. Bold, V. Boldea, N.M. Bolnet, M. Bomben, M. Bona, M. Boonekamp, S. Bordoni, C. Borer, A. Borisov, G. Borissov, I. Borjanovic, M. Borri, S. Borroni, V. Bortolotto, K. Bos, D. Boscherini, M. Bosman, H. Boterenbrood, J. Bouchami, J. Boudreau, E.V. Bouhova-Thacker, D. Boumediene, C. Bourdarios, N. Bousson, A. Boveia, J. Boyd, I.R. Boyko, I. Bozovic-Jelisavcic, J. Bracinik, P. Branchini, G.W. Brandenburg, A. Brandt, G. Brandt, O. Brandt, U. Bratzler, B. Brau, J.E. Brau, H.M. Braun, S.F. Brazzale, B. Brelier, J. Bremer, K. Brendlinger, R. Brenner, S. Bressler, D. Britton, F.M. Brochu, I. Brock, R. Brock, F. Broggi, C. Bromberg, J. Bronner, G. Brooijmans, T. Brooks, W.K. Brooks, G. Brown, H. Brown, P.A. Bruckman de Renstrom, D. Bruncko, R. Bruneliere, S. Brunet, A. Bruni, G. Bruni, M. Bruschi, T. Buanes, Q. Buat, F. Bucci, J. Buchanan, P. Buchholz, R.M. Buckingham, A.G. Buckley, S.I. Buda, I.A. Budagov, B. Budick, V. Büscher, L. Bugge, O. Bulekov, A.C. Bundock, M. Bunse, T. Buran, H. Burckhart, S. Burdin, T. Burgess, S. Burke, E. Busato, P. Bussey, C.P. Buszello, B. Butler, J.M. Butler, C.M. Buttar, J.M. Butterworth, W. Buttinger, S. Cabrera Urbán, D. Caforio, O. Cakir, P. Calafiura, G. Calderini, P. Calfayan, R. Calkins, L.P. Caloba, R. Caloi, D. Calvet, S. Calvet, R. Camacho Toro, P. Camarri, D. Cameron, L.M. Caminada, R. Caminal Armadans, S. Campana, M. Campanelli, V. Canale, F. Canelli, A. Canepa, J. Cantero, R. Cantrill, L. Capasso, M.D.M. Capeans Garrido, I. Caprini, M. Caprini, D. Capriotti, M. Capua, R. Caputo, R. Cardarelli, T. Carli, G. Carlino, L. Carminati, B. Caron, S. Caron, E. Carquin, G.D. Carrillo-Montoya, A.A. Carter, J.R. Carter, J. Carvalho, D. Casadei, M.P. Casado, M. Cascella, C. Caso, A.M. Castaneda Hernandez, E. Castaneda-Miranda, V. Castillo Gimenez, N.F. Castro, G. Cataldi, P. Catastini, A. Catinaccio, J.R. Catmore, A. Cattai, G. Cattani, S. Caughron, V. Cavaliere, P. Cavalleri, D. Cavalli, M. Cavalli-Sforza, V. Cavasinni, F. Ceradini, A.S. Cerqueira, A. Cerri, L. Cerrito, F. Cerutti, S.A. Cetin, A. Chafaq, D. Chakraborty, I. Chalupkova, K. Chan, P. Chang, B. Chapleau, J.D. Chapman, J.W. Chapman, E. Chareyre, D.G. Charlton, V. Chavda, C.A. Chavez Barajas, S. Cheatham, S. Chekanov, S.V. Chekulaev, G.A. Chelkov, M.A. Chelstowska, C. Chen, H. Chen, S. Chen, X. Chen, Y. Chen, Y. Cheng, A. Cheplakov, R. Cherkaoui El Moursli, V. Chernyatin, E. Cheu, S.L. Cheung, L. Chevalier, G. Chiefari, L. Chikovani, J.T. Childers, A. Chilingarov, G. Chiodini, A.S. Chisholm, R.T. Chislett, A. Chitan, M.V. Chizhov, G. Choudalakis, S. Chouridou, I.A. Christidi, A. Christov, D. Chromek-Burckhart, M.L. Chu, J. Chudoba, G. Ciapetti, A.K. Ciftci, R. Ciftci, D. Cinca, V. Cindro, C. Ciocca, A. Ciocio, M. Cirilli, P. Cirkovic, Z.H. Citron, M. Citterio, M. Ciubancan, A. Clark, P.J. Clark, R.N. Clarke, W. Cleland, J.C. Clemens, B. Clement, C. Clement, Y. Coadou, M. Cobal, A. Coccaro, J. Cochran, L. Coffey, J.G. Cogan, J. Coggeshall, E. Cogneras, J. Colas, S. Cole, A.P. Colijn, N.J. Collins, C. Collins-Tooth, J. Collot, T. Colombo, G. Colon, G. Compostella, P. Conde Muiño, E. Coniavitis, M.C. Conidi, S.M. Consonni, V. Consorti, S. Constantinescu, C. Conta, G. Conti, F. Conventi, M. Cooke, B.D. Cooper, A.M. Cooper-Sarkar, N.J. Cooper-Smith, K. Copic, T. Cornelissen, M. Corradi, F. Corriveau, A. Cortes-Gonzalez, G. Cortiana, G. Costa, M.J. Costa, D. Costanzo, D. Côté, L. Courneyea, G. Cowan, C. Cowden, B.E. Cox, K. Cranmer, F. Crescioli, M. Cristinziani, G. Crosetti, S. Crépé-Renaudin, C.-M. Cuciuc, C. Cuenca Almenar, T. Cuhadar Donszelmann, M. Curatolo, C.J. Curtis, C. Cuthbert, P. Cwetanski, H. Czirr, P. Czodrowski, Z. Czyczula, S. DʼAuria, M. DʼOnofrio, A. DʼOrazio, M.J. Da Cunha Sargedas De Sousa, C. Da Via, W. Dabrowski, A. Dafinca, T. Dai, C. Dallapiccola, M. Dam, M. Dameri, D.S. Damiani, H.O. Danielsson, V. Dao, G. Darbo, G.L. Darlea, J.A. Dassoulas, W. Davey, T. Davidek, N. Davidson, R. Davidson, E. Davies, M. Davies, O. Davignon, A.R. Davison, Y. Davygora, E. Dawe, I. Dawson, R.K. Daya-Ishmukhametova, K. De, R. de Asmundis, S. De Castro, S. De Cecco, J. de Graat, N. De Groot, P. de Jong, C. De La Taille, H. De la Torre, F. De Lorenzi, L. de Mora, L. De Nooij, D. De Pedis, A. De Salvo, U. De Sanctis, A. De Santo, J.B. De Vivie De Regie, G. De Zorzi, W.J. Dearnaley, R. Debbe, C. Debenedetti, B. Dechenaux, D.V. Dedovich, J. Degenhardt, C. Del Papa, J. Del Peso, T. Del Prete, T. Delemontex, M. Deliyergiyev, A. DellʼAcqua, L. DellʼAsta, M. Della Pietra, D. della Volpe, M. Delmastro, P. Delpierre, P.A. Delsart, C. Deluca, S. Demers, M. Demichev, B. Demirkoz, J. Deng, S.P. Denisov, D. Derendarz, J.E. Derkaoui, F. Derue, P. Dervan, K. Desch, E. Devetak, P.O. Deviveiros, A. Dewhurst, B. DeWilde, S. Dhaliwal, R. Dhullipudi, A. Di Ciaccio, L. Di Ciaccio, C. Di Donato, A. Di Girolamo, B. Di Girolamo, S. Di Luise, A. Di Mattia, B. Di Micco, R. Di Nardo, A. Di Simone, R. Di Sipio, M.A. Diaz, E.B. Diehl, J. Dietrich, T.A. Dietzsch, S. Diglio, K. Dindar Yagci, J. Dingfelder, F. Dinut, C. Dionisi, P. Dita, S. Dita, F. Dittus, F. Djama, T. Djobava, M.A.B. do Vale, A. Do Valle Wemans, T.K.O. Doan, M. Dobbs, R. Dobinson, D. Dobos, E. Dobson, J. Dodd, C. Doglioni, T. Doherty, Y. Doi, J. Dolejsi, I. Dolenc, Z. Dolezal, B.A. Dolgoshein, T. Dohmae, M. Donadelli, J. Donini, J. Dopke, A. Doria, A. Dos Anjos, A. Dotti, M.T. Dova, J.D. Dowell, A.D. Doxiadis, A.T. Doyle, N. Dressnandt, M. Dris, J. Dubbert, S. Dube, E. Duchovni, G. Duckeck, D. Duda, A. Dudarev, F. Dudziak, M. Dührssen, I.P. Duerdoth, L. Duflot, M.-A. Dufour, L. Duguid, M. Dunford, H. Duran Yildiz, R. Duxfield, M. Dwuznik, F. Dydak, M. Düren, W.L. Ebenstein, J. Ebke, S. Eckweiler, K. Edmonds, W. Edson, C.A. Edwards, N.C. Edwards, W. Ehrenfeld, T. Eifert, G. Eigen, K. Einsweiler, E. Eisenhandler, T. Ekelof, M. El Kacimi, M. Ellert, S. Elles, F. Ellinghaus, K. Ellis, N. Ellis, J. Elmsheuser, M. Elsing, D. Emeliyanov, R. Engelmann, A. Engl, B. Epp, J. Erdmann, A. Ereditato, D. Eriksson, J. Ernst, M. Ernst, J. Ernwein, D. Errede, S. Errede, E. Ertel, M. Escalier, H. Esch, C. Escobar, X. Espinal Curull, B. Esposito, F. Etienne, A.I. Etienvre, E. Etzion, D. Evangelakou, H. Evans, L. Fabbri, C. Fabre, R.M. Fakhrutdinov, S. Falciano, Y. Fang, M. Fanti, A. Farbin, A. Farilla, J. Farley, T. Farooque, S. Farrell, S.M. 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Yoshihara, C. Young, C.J. Young, S. Youssef, D. Yu, J. Yu, J. Yu, L. Yuan, A. Yurkewicz, M. Byszewski, B. Zabinski, R. Zaidan, A.M. Zaitsev, Z. Zajacova, L. Zanello, D. Zanzi, A. Zaytsev, C. Zeitnitz, M. Zeman, A. Zemla, C. Zendler, O. Zenin, T. Ženiš, Z. Zinonos, D. Zerwas, G. Zevi della Porta, D. Zhang, H. Zhang, J. Zhang, X. Zhang, Z. Zhang, L. Zhao, Z. Zhao, A. Zhemchugov, J. Zhong, B. Zhou, N. Zhou, Y. Zhou, C.G. Zhu, H. Zhu, J. Zhu, Y. Zhu, X. Zhuang, V. Zhuravlov, D. Zieminska, N.I. Zimin, R. Zimmermann, S. Zimmermann, S. Zimmermann, M. Ziolkowski, R. Zitoun, L. Živković, V.V. Zmouchko, G. Zobernig, A. Zoccoli, M. zur Nedden, V. Zutshi, L. Zwalinski

ANPCyT, YerPhI, ARC, BMWF, ANAS, SSTC, CNPq, FAPESP, NSERC, NRC, CFI, CERN, CONICYT, CAS, MOST, NSFC, COLCIENCIAS, MSMT CR, MPO CR, VSC CR, DNRF, DNSRC, Lundbeck Foundation, EPLANET, ERC, IN2P3-CNRS, CEA-DSM/IRFU, GNAS, BMBF, DFG, HGF, MPG, AvH Foundation, GSRT, ISF, MINERVA, GIF, DIP, Benoziyo Center, INFN, MEXT, JSPS, CNRST, FOM, NWO, RCN, MNiSW, GRICES, FCT, MERYS (MECTS), MES of Russia, ROSATOM, JINR, MSTD, MSSR, ARRS, MVZT, DST/NRF, MICINN, SRC, Wallenberg Foundation, SER, SNSF, Cantons of Bern and Geneva, NSC, TAEK, STFC, Royal Society, Leverhulme Trust, DOE, NSF


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Nam Joong Jeon, Jun Hong Noh, Young Chan Kim, Woon Seok Yang, Seungchan Ryu, Sang Il Seok


A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

G P Dimri, X Lee, G Basile, M Acosta, G Scott, C Roskelley, E E Medrano, M Linskens, I Rubelj, O Pereira-Smith

Department of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.

Abstract: Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.


Interface engineering of highly efficient perovskite solar cells

Huanping Zhou, Qi Chen, Gang Li, Song Luo, Tze-bing Song, Hsin-Sheng Duan, Ziruo Hong, Jingbi You, Yongsheng Liu, Yang Yang

Department of Materials Science and Engineering, University of California, Los Angeles, CA 90095, USA.

Abstract: A layered approach improves solar cells Perovskite films received a boost in photovoltaic efficiency through controlled formation of charge-generating films and improved current transfer to the electrodes. Zhou et al. lowered the defect density of the film by controlling humidity while the perovskite film formed from lead chloride and methylammonium iodide. Low-temperature processing steps allowed the use of materials that draw current out of the perovskite layer more efficiently. These and other modifications enabled a maximum cell efficiency of just over 19% and an average of 16.6%. Science , this issue p. 542


A scalable Bayesian functional GWAS method accounting for multivariate quantitative functional annotations with applications for studying Alzheimer disease

Junyu Chen, Lei Wang, Philip L. De Jager, David A. Bennett, Aron S. Buchman, Jingjing Yang

National Institute on Aging, National Institute on Aging, National Institute on Aging, National Institute on Aging, National Institute on Aging, National Institute on Aging, National Institute on Aging, National Institute on Aging, National Institute on Aging, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Translational Genomics Research Institute, Mayo Foundation for Medical Education and Research, Illinois Department of Public Health, National Institutes of Health, NIGMS, National Institute of Neurological Disorders and Stroke


Identification of 15 candidate structured noncoding RNA motifs in fungi by comparative genomics

National Institutes of Health, Howard Hughes Medical Institute


Large indel detection in region-based phased diploid assemblies from linked-reads

Can Luo, Brock A. Peters, Xin Maizie Zhou

National Institutes of Health, Complete Genomics

Abstract: Abstract Background Linked-reads improve de novo assembly, haplotype phasing, structural variant (SV) detection, and other applications through highly-multiplexed genome partitioning and barcoding. Whole genome assembly and assembly-based variant detection based on linked-reads often require intensive computation costs and are not suitable for large population studies. Here we propose an efficient pipeline, RegionIndel, a region-based diploid assembly approach to characterize large indel SVs. This pipeline only focuses on target regions (50kb by default) to extract barcoded reads as input and then integrates a haplotyping algorithm and local assembly to generate phased diploid contiguous sequences (contigs). Finally, it detects variants in the contigs through a pairwise contig-to-reference comparison. Results We applied RegionIndel on two linked-reads libraries of sample HG002, one using 10x and the other stLFR. HG002 is a well-studied sample and the Genome in a Bottle (GiaB) community provides a gold standard SV set for it. RegionIndel outperformed several assembly and alignment-based SV callers in our benchmark experiments. After assembling all indel SVs, RegionIndel achieved an overall F1 score of 74.8% in deletions and 61.8% in insertions for 10x linked-reads, and 64.3% in deletions and 36.7% in insertions for stLFR linked-reads, respectively. Furthermore, it achieved an overall genotyping accuracy of 83.6% and 80.8% for 10x and stLFR linked-reads, respectively. Conclusions RegionIndel can achieve diploid assembly and detect indel SVs in each target region. The phased diploid contigs can further allow us to investigate indel SVs with nearby linked single nucleotide polymorphism (SNPs) and small indels in the same haplotype.


The role of DNA repair in herpesvirus pathogenesis


The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health

Kristin Bornstein, Gary Gryan, E. Sally Chang, Aron Marchler-Bauer, Valerie A. Schneider

National Center for Biotechnology Information (NCBI) of the National Library of Medicine (NLM), National Institutes of Health, National Institutes of Health

Abstract: AbstractComparative genomics is the comparison of genetic information within and across organisms to understand the evolution, structure, and function of genes, proteins, and non-coding regions (Sivashankari and Shanmughavel, Bioinformation 1:376-8, 2007). Advances in sequencing technology and assembly algorithms have resulted in the ability to sequence large genomes and provided a wealth of data that are being used in comparative genomic analyses. Comparative analysis can be leveraged to systematically explore and evaluate the biological relationships and evolution between species, aid in understanding the structure and function of genes, and gain a better understanding of disease and potential drug targets. As our knowledge of genetics expands, comparative genomics can help identify emerging model organisms among a broader span of the tree of life, positively impacting human health. This impact includes, but is not limited to, zoonotic disease research, therapeutics development, microbiome research, xenotransplantation, oncology, and toxicology. Despite advancements in comparative genomics, new challenges have arisen around the quantity, quality assurance, annotation, and interoperability of genomic data and metadata. New tools and approaches are required to meet these challenges and fulfill the needs of researchers. This paper focuses on how the National Institutes of Health (NIH) Comparative Genomics Resource (CGR) can address both the opportunities for comparative genomics to further impact human health and confront an increasingly complex set of challenges facing researchers.


SoMaCX: a complex generative genome modeling framework


Transcriptional regulation of mammalian miRNA genes


Neurotranscriptome profiles of multiple zebrafish strains


Controlling for conservation in genome-wide DNA methylation studies


Finding RNA structure in the unstructured RBPome

Yaron Orenstein, Uwe Ohler, Bonnie Berger


Integrating ChIP-seq with other functional genomics data


Double or nothing: Ancient duplications in the amylase locus drove human adaptation


Better together: Non-additive interactions between schizophrenia risk genes


Disease consequences of human adaptation


CrossFilt: A Cross-species Filtering Tool that Eliminates Alignment Bias in Comparative Genomics Studies

Department of Medicine, University of Chicago; Chicago, IL 60637, USA

National Institutes of Health, National Institutes of Health

Abstract: Abstract Comparative functional genomic studies are often affected by biased read mapping across species due to inter-species differences in genome structure, sequence composition, and annotation quality. We developed CrossFilt, a filtering strategy that retains only sequencing reads that map reciprocally between genomes, ensuring that quantification of read counts is based on directly comparable genomic features. Using both real and simulated RNA-sequencing data from primates, we show that CrossFilt outperforms five alternative approaches that are commonly used, resulting in more accurate inference of gene expression differences. Our results highlight the impact of preprocessing strategies on the analysis of cross-species functional genomics data.


Predicting the combined effect of multiple genetic variants

Mingming Liu, Layne T. Watson, Liqing Zhang


Using genetics, genomics, and transcriptomics to identify therapeutic targets in juvenile idiopathic arthritis

Rheumatology Research Foundation, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases


Leveraging our common African origins to understand human evolution and health


5-Hydroxymethylcytosine: A stable or transient DNA modification?

Maria A. Hahn, Piroska E. Szabó, Gerd P. Pfeifer


Sampling a wide swathe of primate genetic diversity


Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

Abstract: AbstractBackgroundDeciphering gene regulation is essential for understanding the underlying mechanisms of healthy and disease states. While the regulatory networks formed by transcription factors (TFs) and their target genes has been mostly studied with relation tociseffects such as in TF binding sites, we focused ontranseffects of TFs on the expression of their transcribed genes and their potential mechanisms.ResultsWe provide a comprehensive tissue-specific atlas, spanning 49 tissues of TF variations affecting gene expression through computational models considering two potential mechanisms, including combinatorial regulation by the expression of the TFs, and by genetic variants within the TF.We demonstrate that similarity between tissues based on our discovered genes corresponds to other types of tissue similarity. The genes affected by complex TF regulation, and their modelled TFs, were highly enriched for pharmacogenomic functions, while the TFs themselves were also enriched in several cancer and metabolic pathways. Additionally, genes that appear in multiple clusters are enriched for regulation of immune system while tissue clusters include cluster-specific genes that are enriched for biological functions and diseases previously associated with the tissues forming the cluster. Finally, our atlas exposes multilevel regulation across multiple tissues, where TFs regulate other TFs through the two tested mechanisms.ConclusionsOur tissue-specific atlas provides hierarchical tissue-specifictransgenetic regulations that can be further studied for association with human phenotypes.


The Drosophila transcriptional network is structured by microbiota

Adam J. Dobson, John M. Chaston, Angela E. Douglas


Deciphering epigenomic code for cell differentiation using deep learning

National Science Foundation, National Institutes of Health

Abstract: Abstract Background Although DNA sequence plays a crucial role in establishing the unique epigenome of a cell type, little is known about the sequence determinants that lead to the unique epigenomes of different cell types produced during cell differentiation. To fill this gap, we employed two types of deep convolutional neural networks (CNNs) constructed for each of differentially related cell types and for each of histone marks measured in the cells, to learn the sequence determinants of various histone modification patterns in each cell type. Results We applied our models to four differentially related human CD 4 + T cell types and six histone marks measured in each cell type. The cell models can accurately predict the histone marks in each cell type, while the mark models can also accurately predict the cell types based on a single mark. Sequence motifs learned by both the cell or mark models are highly similar to known binding motifs of transcription factors known to play important roles in CD 4 + T cell differentiation. Both the unique histone mark patterns in each cell type and the different patterns of the same histone mark in different cell types are determined by a set of motifs with unique combinations. Interestingly, the level of sharing motifs learned in the different cell models reflects the lineage relationships of the cells, while the level of sharing motifs learned in the different histone mark models reflects their functional relationships. These models can also enable the prediction of the importance of learned motifs and their interactions in determining specific histone mark patterns in the cell types. Conclusion Sequence determinants of various histone modification patterns in different cell types can be revealed by comparative analysis of motifs learned in the CNN models for multiple cell types and histone marks. The learned motifs are interpretable and may provide insights into the underlying molecular mechanisms of establishing the unique epigenomes in different cell types. Thus, our results support the hypothesis that DNA sequences ultimately determine the unique epigenomes of different cell types through their interactions with transcriptional factors, epigenome remodeling system and extracellular cues during cell differentiation.


Identification of imprinting regulators at the Meg3 differentially methylated region


Data-driven projections of candidate enhancer-activating SNPs in immune regulation

Markus Hoffmann, Tiago Vaz, Shreeti Chhatrala, Lothar Hennighausen

Abstract: Abstract Background Millions of single nucleotide polymorphisms (SNPs) have been identified in humans, but the functionality of almost all SNPs remains unclear. While current research focuses primarily on SNPs altering one amino acid to another one, the majority of SNPs are located in intergenic spaces. Some of these SNPs can be found in candidate cis-regulatory elements (CREs) such as promoters and enhancers, potentially destroying or creating DNA-binding motifs for transcription factors (TFs) and, hence, deregulating the expression of nearby genes. These aspects are understudied due to the sheer number of SNPs and TF binding motifs, making it challenging to identify SNPs that yield phenotypic changes or altered gene expression. Results We developed a data-driven computational protocol to prioritize high-potential SNPs informed from former knowledge for experimental validation. We evaluated the protocol by investigating SNPs in CREs in the Janus kinase (JAK) – Signal Transducer and Activator of Transcription (-STAT) signaling pathway, which is activated by a plethora of cytokines and crucial in controlling immune responses and has been implicated in diseases like cancer, autoimmune disorders, and responses to viral infections. The protocol involves scanning the entire human genome (hg38) to pinpoint DNA sequences that deviate by only one nucleotide from the canonical binding sites (TTCnnnGAA) for STAT TFs. We narrowed down from an initial pool of 3,301,512 SNPs across 17,039,967 nearly complete STAT motifs and identified six potential gain-of-function SNPs in regions likely to influence regulation within the JAK-STAT pathway. This selection was guided by publicly available open chromatin and gene expression data and further refined by filtering for proximity to immune response genes and conservation between the mouse and human genomes. Conclusion Our findings highlight the value of combining genomic, epigenomic, and cross-species conservation data to effectively narrow down millions of SNPs to a smaller number with a high potential to induce interferon regulation of nearby genes. These SNPs can finally be reviewed manually, laying the groundwork for a more focused and efficient exploration of regulatory SNPs in an experimental setting.


Implementing differentially pigmented skin models for predicting drug response variability across human ancestries


Inference of kinship using spatial distributions of SNPs for genome-wide association studies


Decoupling behavioral and transcriptional responses to color in an eyeless cnidarian

Abstract: AbstractBackgroundAnimals have specific molecular, physiological, and behavioral responses to light that are influenced by wavelength and intensity. Predictable environmental changes – predominantly solar and lunar cycles – drive endogenous daily oscillations by setting internal pacemakers, otherwise known as the circadian clock. Cnidarians have been a focal group to discern the evolution of light responsiveness due to their phylogenetic position as a sister phylum to bilaterians and broad range of light-responsive behaviors and physiology. Marine species that occupy a range of depths will experience different ranges of wavelengths and light intensities, which may result in variable phenotypic responses. Here, we utilize the eyeless sea anemoneNematostella vectensis, an estuarine anemone that typically resides in shallow water habitats, to compare behavioral and molecular responses when exposed to different light conditions.ResultsQuantitative measures of locomotion clearly showed that this species responds to light in the blue and green spectral range with a circadian activity profile, in contrast to a circatidal activity profile in the red spectral range and in constant darkness. Differences in average day/night locomotion was significant in each condition, with overall peak activity during the dark period. Comparative analyses of 96 transcriptomes from individuals sampled every 4 h in each lighting treatment revealed complex differences in gene expression between colors, including in many of the genes likely involved in the cnidarian circadian clock. Transcriptional profiling showed the majority of genes are differentially expressed when comparing mid-day with mid-night, and mostly in red light. Gene expression profiles were largely unique in each color, although animals in blue and green were overall more similar to each other than to red light.ConclusionsTogether, these analyses support the hypothesis that cnidarians are sensitive to red light, and this perception results in a rich transcriptional and divergent behavioral response. Future work determining the specific molecular mechanisms driving the circadian and potential circatidal rhythms measured here would be impactful to connect gene expression variation with behavioral variation in this eyeless species.


Taxonomic distribution and evolutionary analysis of the equol biosynthesis gene cluster

Keith Dufault-Thompson, Brantley Hall, Xiaofang Jiang

Abstract: Abstract Background Equol, an isoflavonoid metabolite with possible health benefits in humans, is known to be produced by some human gut bacteria. While the genes encoding the equol production pathway have been characterized in a few bacterial strains, a systematic analysis of the equol production pathway is currently lacking. Results This study presents an analysis of the taxonomic distribution and evolutionary history of the gene cluster encoding the equol production pathway. A survey for equol gene clusters within the Genome Taxonomy Database bacterial genomes and human gut metagenomes resulted in the identification of a highly conserved gene cluster found in nine bacterial species from the Eggerthellaceae family. The identified gene clusters from human gut metagenomes revealed potential variations in the equol gene cluster organization and gene content within the equol-producing Eggerthellaceae clades. Subsequent analysis showed that in addition to the four genes directly involved in equol production, multiple other genes were consistently found in the equol gene clusters. These genes were predicted to encode a putative electron transport complex and hydrogenase maturase system, suggesting potential roles for them in the equol production pathway. Analysis of the gene clusters and a phylogenetic reconstruction of a putative NAD kinase gene provided evidence of the recent transfer of the equol gene cluster from a basal Eggerthellaceae species to Slackia_A equolifaciens, Enteroscipio sp000270285, and Lactococcus garvieae 20–92. Conclusions This analysis demonstrates that the highly conserved equol gene cluster is taxonomically restricted to the Eggerthellaceae family of bacteria and provides evidence of the role of horizontal gene transfer in the evolutionary history of these genes. These results provide a foundation for future studies of equol production in the human gut and future efforts related to bioengineering and the use of equol-producing bacteria as probiotics.


DNA methyltransferases in hematological malignancies


Mapping disease loci to biological processes via joint pleiotropic and epigenomic partitioning

Gaspard Kerner, Nolan Kamitaki, Benjamin Strober, Alkes L. Price


Genotype-expression interactions for BDNF across human brain regions

Patrick Devlin, Xueyuan Cao, Ansley Grimes Stanfill

Abstract: AbstractBackgroundGenetic variations in brain-derived neurotrophic factor (BDNF) are associated with various psychiatric disorders including depression, obsessive-compulsive disorder, substance use disorders, and schizophrenia; altered gene expression triggered by these genetic variants may serve to create these phenotypes. But genotype-expression interactions for this gene have not been well-studied across brain regions relevant for psychiatric disorders.ResultsAt false discovery rate (FDR) of 10% (q < 0.1), a total of 61 SNPs were associated withBDNFexpression in cerebellum (n = 209), 55 SNPs in cortex (n = 205), 48 SNPs in nucleus accumbens (n = 202), 47 SNPs in caudate (n = 194), and 58 SNPs in cerebellar hemisphere (n = 175). We identified a set of 30 SNPs in 2 haplotype blocks that were associated with alterations in expression for each of these 5 regions. The first haplotype block included variants associated in the literature with panic disorders (rs16917204), addiction (rs11030104), bipolar disorder (rs16917237/rs2049045), and obsessive-compulsive disorder (rs6265). Likewise, variants in the second haplotype block have been previously associated with disorders such as nicotine addiction, major depressive disorder (rs988748), and epilepsy (rs6484320/rs7103411).ConclusionsThis work supports the association of variants withinBDNFfor expression changes in these key brain regions that may contribute to common behavioral phenotypes for disorders of compulsion, impulsivity, and addiction. These SNPs should be further investigated as possible therapeutic and diagnostic targets to aid in management of these and other psychiatric disorders.


Molecular subtyping of leiomyosarcoma with 3′ end RNA sequencing

Xiangqian Guo, Erna Forgó, Matt van de Rijn


Evaluating genetic ancestry inference from single-cell transcriptomic datasets


Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species

Anthony Mannion, Zeli Shen, James G. Fox

National Institutes of Health, National Institutes of Health, National Institutes of Health, National Institutes of Health


The DNA methylation landscape of human melanoma

Seung-Gi Jin, Wenying Xiong, Xiwei Wu, Lu Yang, Gerd P. Pfeifer


Understanding hypertensive renal injury: a well-structured approach

University of Texas Health Science Center at Houston


Rapid discrimination between deleterious and benign missense mutations in the CAGI 6 experiment

Eshel Faraggi, Robert L. Jernigan, Andrzej Kloczkowski


Clustering multilayer omics data using MuNCut

National Institutes of Health, National Bureau of Statistics of China


A repetitive DNA-directed program of chromosome packaging during mitosis


Complement regulator CD46: genetic variants and disease associations


COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy

Giuseppe Novelli, Michela Biancolella, Ruty Mehrian-Shai, Vito Luigi Colona, Anderson F. Brito, Nathan D. Grubaugh, Vasilis Vasiliou, Lucio Luzzatto, Juergen K. V. Reichardt

National Institutes of Health, Fondazione Roma

Abstract: AbstractCOVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.


Gene expression profiling of U2AF2 dependent RNA-protein interactions during CD4 + T cell activation


Update of the sideroflexin (SLC56) gene family

Angeliki I. Katsafadou, Daniel W. Nebert, Sergey A. Krupenko, David C. Thompson, Vasilis Vasiliou


Multilocus molecular mapping of the mouse X chromosome

Linda J. Mullins, Stephen G. Grant, Dennis A. Stephenson, Verne M. Chapman


Enhancer jungles establish robust tissue-specific regulatory control in the human genome

National Institutes of Health, U.S. National Library of Medicine


Genome-wide positioning of bivalent mononucleosomes

Subhojit Sen, Kirsten F. Block, Alice Pasini, Stephen B. Baylin, Hariharan Easwaran


The audacity of interpretation: Protecting patients or piling on?


Comparative genomics of tadpole shrimps (Crustacea, Branchiopoda, Notostraca): Dynamic genome evolution against the backdrop of morphological stasis

Andrea Luchetti, Giobbe Forni, Jacopo Martelossi, Castrense Savojardo, Pier Luigi Martelli, Rita Casadio, Alyza M. Skaist, Sarah J. Wheelan, Barbara Mantovani

National Cancer Institute, Indiana University, National Institutes of Health


Epigenetic and genetic alterations and their influence on gene regulation in chronic lymphocytic leukemia


Portuguese History Teachers’ Ideas about History


COMPARATIVE HISTORY AND WOMEN’S HISTORY


THE HISTORY OF ECONOMICS AND THE HISTORY OF AGENCY


History, Memory and Learning to Teach


HISTORY


WHAT HISTORY IS


History, citizenship and diversity


Taiwanese Students’ Understanding of Differences in History Textbook Accounts


The Epistemological Reach of the History Teacher


The sound of guns


COMPARING AND GENERALIZING


Introduction


INTRODUCTION

THE DISCIPLINE OF HISTORY AND THE HISTORY OF THOUGHT


HISTORY OF PHILOSOPHY AND HISTORY OF IDEAS


Citizenship, political literacy and history


DOING HISTORY IN THE POST-MODERN WORLD


‘Till New Facts are Discovered’


Understanding the Knowledge Bases of History Teaching

ANNA PENDRY, CHRIS HUSBANDS, ALISON KITSON


The history teacher and global citizenship


Architectural history


The study of Earth history


COMPARATIVE HISTORY


INTRODUCTION


A Revolutionary history


THE HISTORY OF CLASSICAL AND FREQUENTIST THEORIES OF PROBABILITY


STORYTELLING IN HISTORY

HISTORY AND ENGLISH IN THE PRIMARY SCHOOL


Conclusion


Citizenship education and the teaching and learning of history


Students’ Approaches to Validating Historical Claims


British History as a ‘new subject’


HISTORY, ANALOGY, AND POLICY REALISM


TOWARD A HISTORY OF AMERICANIST LINGUISTICS

TOWARD A HISTORY OF AMERICAN LINGUISTICS


Securing a place for citizenship education in the history department


Communitarianism and the teaching of history


The Early History of the Synapse


‘Marxism is not a “Science of History”’


THE EARLIER HISTORY OF MONEY


XENOPHON, HISTORY AND ORDER


REFLECTIONS ON SCHUMPETER’S<i>HISTORY OF ECONOMIC ANALYSIS</i>IN LIGHT OF HIS UNIVERSAL SOCIAL SCIENCE


WRITING ABOUT HISTORY IN THE EARLY YEARS


Children’s Understanding of Historical Narrative in Portugal


RMA Anatomy


HISTORY AND CHILDREN’S FICTION


IS THERE A PRE-HISTORY OF GLOBALIZATION?


Teaching and learning European citizenship in history lessons


HISTORY, CONTINGENCY, AND THE ROOTS OF REALISM


Approaching extremism


The moral dimensions of promoting citizenship through the teaching of history


HISTORY


Resting-State fMRI Using Passband Balanced Steady-State Free Precession

Joe S. Cheng, Patrick P. Gao, Iris Y. Zhou, Russell W. Chan, Queenie Chan, Henry K. Mak, Pek L. Khong, Ed X. Wu


Analysis of Human RSV Immunity at the Molecular Level: Learning from the Past and Present

Kerrie Vaughan, Julia Ponomarenko, Bjoern Peters, Alessandro Sette


Towards a Hierarchical Strategy to Explore Multi-Scale IP/MS Data for Protein Complexes

Joachim Kutzera, Age K. Smilde, Tom F. Wilderjans, Huub C. J. Hoefsloot


Cryptic Contamination and Phylogenetic Nonsense

Anna Linderholm, Helena Malmström, Kerstin Lidén, Gunilla Holmlund, Anders Götherström


Early Biodistribution and Persistence of a Protective Live Attenuated SIV Vaccine Elicits Localised Innate Responses in Multiple Lymphoid Tissues

Deborah Ferguson, Giada Mattiuzzo, Claire Ham, Richard Stebbings, Bo Li, Nicola J. Rose, Edward T. Mee, Deborah Smith, Mark Page, Martin P. Cranage, Neil Almond, Greg J. Towers, Neil J. Berry


Protein Interactions and Regulation of EscA in Enterohemorrhagic E. coli

Ching-Nan Lin, Wei-Sheng W. Sun, Hui-Yin Lu, Swee-Chuan Ng, Ying-Shu Liao, Wan-Jr Syu


Rescue the Failed Half-ZFN by a Sensitive Mammalian Cell-Based Luciferase Reporter System

Weifeng Zhang, Yuanxu Guo, Chen Zhang, Haiyan Ji, Wenpeng Meng, Dongyang Wang, Xing Li, Qinwen Mao, Haibin Xia


Differences in Statin Usage and Target-Goal Achievement between Departments at the Same Hospital

Zhong Chen, Xin Wang, Zhen Ding, Peiying Fan, Genshan Ma


Disruption of Glycerol Metabolism by RNAi Targeting of Genes Encoding Glycerol Kinase Results in a Range of Phenotype Severity in Drosophila

Patrick J. Wightman, George R. Jackson, Katrina M. Dipple


Characterization of Resistance to Rhabdovirus and Retrovirus Infection in a Human Myeloid Cell Line


Regulation of Gag- and Env-Specific CD8+ T Cell Responses in ART-Naïve HIV-Infected Patients: Potential Implications for Individualized Immunotherapy

Christian Prebensen, Andreas Lind, Anne-Ma Dyrhol-Riise, Dag Kvale


Common Immunosuppressive Monotherapy for Graves’ Ophthalmopathy: A Meta-Analysis

Pei Mou, Li-Hong Jiang, Yun Zhang, Yu-Zhen Li, Heng Lou, Cheng-Cheng Zeng, Qiu-Hong Wang, Jin-Wei Cheng, Rui-Li Wei


NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF

Xue-Lian Lin, Xu-Dong Tang, Zheng-Xu Cai, Feng-Yun Wang, Ping Li, Hua Sui, Hui-Shu Guo


Rebuttal to the Formal Comment on Schorr et al. (2014) submitted by Tyack et al. (2015)

Gregory S. Schorr, Erin A. Falcone, David J. Moretti, Russel D. Andrews


Dominance of Orientation over Frequency in the Perception of 3-D Slant and Shape


Inferring the Population Expansions in Peopling of Japan


Mechanisms Underlying Stage-1 TRPL Channel Translocation in Drosophila Photoreceptors

Minh-Ha Lieu, Maximiliano J. Vallejos, Emily Michael, Susan Tsunoda


Functional Pathway Analysis Using SCNP of FLT3 Receptor Pathway Deregulation in AML Provides Prognostic Information Independent from Mutational Status

Alessandra Cesano, Santosh Putta, David B. Rosen, Aileen C. Cohen, Urte Gayko, Kavita Mathi, John Woronicz, Rachael E. Hawtin, Larry Cripe, Zhuoxin Sun, Martin S. Tallman, Elisabeth Paietta


A Genome-Wide Analysis of Array-Based Comparative Genomic Hybridization (CGH) Data to Detect Intra-Species Variations and Evolutionary Relationships


Snoring and Glaucoma

Ya Xing Wang, Liang Xu, Jian Jun Li, Hua Yang, Ya Qin Zhang, Jost B. Jonas


Neonatal Androgenization Exacerbates Alcohol-Induced Liver Injury in Adult Rats, an Effect Abrogated by Estrogen

Whitney M. Ellefson, Ashley M. Lakner, Alicia Hamilton, Iain H. McKillop, Herbert L. Bonkovsky, Nury M. Steuerwald, Yvette M. Huet, Laura W. Schrum


Analysis of IL-6, STAT3 and HSPA1L Gene Polymorphisms in Anti-Tuberculosis Drug-Induced Hepatitis in a Nested Case-Control Study

Jing Wang, Ru Chen, Shaowen Tang, Xiaozhen Lv, Shanshan Wu, Yuan Zhang, Yinyin Xia, Pei Gao, Dehua Tu, Dafang Chen, Siyan Zhan


Combining Evidence of Preferential Gene-Tissue Relationships from Multiple Sources

Jing Guo, Mårten Hammar, Lisa Öberg, Shanmukha S. Padmanabhuni, Marcus Bjäreland, Daniel Dalevi


Inverse association of dietary consumption of n3 and n6 fatty acids with hyperuricemia among adults

Huakai Wang, Chao Zhang, Yuxin Sun, Sirui Sun, Zhe Wang, Honggang Xiang

National Natural Science Foundation of China, Technology Development Project of Pudong Science, Technology and Economic Commission of Shanghai, Outstanding Leaders Training Program of Pudong Health Commission of Shanghai

Abstract: Background The precise link between dietary consumption of n-3 and n-6 fatty acids and hyperuricemia remains equivocal. Accordingly, the purpose of the current investigation is to clarify any possible associations between the consumption of n-3 and n-6 fatty acids and hyperuricemia in the context of American adults. Materials and methods The present investigation employed a cross-sectional design, comprising a sample of 21,120 American adults above the age of 20 from the National Health and Nutrition Examination Survey (NHANES) waves between 2007 and 2016. The dietary consumption of n-3 and n-6 fatty acids was measured through two 24-h dietary recall interviews. To assess the relationships of dietary consumption of n3 and n6 fatty acids with hyperuricemia, we applied multivariable logistic regression, t tests, chi-square tests, and restricted cubic spline. To determine the robustness of our findings, sensitivity analyses were also carried out. Results The results of the multivariable logistic regression models indicated a significant correlation between dietary consumption of n3 and n6 fatty acids and hyperuricemia. The ORs with 95% CIs of hyperuricemia for the highest tertile versus lowest tertile of dietary consumption of n3 and n6 fatty acids were 0.76 (0.66, 0.88) (p < 0.001) and 0.72 (0.64, 0.82) (p < 0.001), respectively. Moreover, dose‒response analyses revealed a linear relationship between n-3 and n-6 fatty acid consumption and the risk of hyperuricemia. Conclusion The findings of this study indicate a significant inverse correlation between the dietary consumption of n3 and n6 fatty acids and hyperuricemia in the US adult population. Notably, there was no significant relationship between the n6:n3 ratio and hyperuricemia.


A Class Representative Model for Pure Parsimony Haplotyping under Uncertain Data

Daniele Catanzaro, Martine Labbé, Luciano Porretta


Scalable and rapid nearest neighbor particle search using adaptive disk sector

Abstract: In this paper, we propose a framework for efficiently accelerating Nearest Neighbor Particle (NNP) calculations in a movable particle-based system by leveraging the dynamic changes in disk sectors. The NNP region based on particles and disk sectors is determined by the following three conditions: 1) The position of the disk resides within the range of neighbor particles. 2) The position of a neighbor particle exists within a disk sector. 3) A neighbor particle exists between the two vectors that form the disk sector. When all of these conditions are satisfied, we assume that there is a particle within the disk sector. In this paper, we automatically update the inspection range of NNP, which is the disk sector, based on the movement of particles. To calculate the dynamic changes in the disk sector, we control the direction, length, and angle of the disk based on the positions and velocities of particles. Ultimately, we accelerate the computation of NNP by utilizing the particles located within the calculated disk sector. The proposed acceleration method can be implemented simply, as it operates on the particles within the disk sector using closed-form expressions, without the explicit data structures like trees. Especially in the case of movable particles, unlike the conventional adaptive tree approach that requires continuous data structure updates, the proposed method can be efficiently utilized in applications requiring NNP. This is because it rapidly calculates collision areas using closed-form expressions that are adjusted according to the particles’ motion. Our method yielded results that were 2 to 20 times faster compared to Hash tables or K-d trees in experiments conducted across diverse scenes. Furthermore, its scalability was demonstrated through its application in various scenarios (particle-based fluids, splash and foam, isoline tracking, turbulent flow, collision handling).


A Simple Model for the Influence of Meiotic Conversion Tracts on GC Content


Netrin-1 – DCC Signaling Systems and Age-Related Macular Degeneration

John Paul SanGiovanni, Jing Chen, Ankur S. Gupta, Lois E. H. Smith, Przemyslaw Sapieha, Phil H. Lee


Extensive Field Survey, Laboratory and Greenhouse Studies Reveal Complex Nature of Pseudomonas syringae-Associated Hazelnut Decline in Central Italy

Jay Ram Lamichhane, Claudia Bartoli, Leonardo Varvaro


Effect of High-Frequency Stimulation of the Perforant Path on Previously Acquired Spatial Memory in Rats: Influence of Memory Strength and Reactivation


The Effects of the Shape and Size of the Clinical Target Volume on the Planning Target Volume Margin


Bovine Lactoferrin Decreases Cholera-Toxin-Induced Intestinal Fluid Accumulation in Mice by Ganglioside Interaction

Fulton P. Rivera, Anicia M. Medina, Sandra Bezada, Roberto Valencia, María Bernal, Rina Meza, Ryan C. Maves, Theresa J. Ochoa


Presence of IgG Anti-gp160/120 Antibodies Confers Higher HIV Capture Capacity to Erythrocytes from HIV-Positive Individuals

Maria Noé Garcia, Maria Sol dos Ramos Farias, Lucia Fazzi, Daniel Grasso, Roberto Daniel Rabinovich, Maria Mercedes Ávila


Do Randomized Controlled Trials Discuss Healthcare Costs?

G. Michael Allan, Christina Korownyk, Kate LaSalle, Ben Vandermeer, Victoria Ma, Douglas Klein, Donna Manca


A Reconstruction Method Based on AL0FGD for Compressed Sensing in Border Monitoring WSN System

Yan Wang, Xi Wu, Wenzao Li, Yi Zhang, Zhi Li, Jiliu Zhou


Fabrication of Dense Non-Circular Nanomagnetic Device Arrays Using Self-Limiting Low-Energy Glow-Discharge Processing

Zhen Zheng, Long Chang, Ivan Nekrashevich, Paul Ruchhoeft, Sakhrat Khizroev, Dmitri Litvinov


Unique Profile of Ordered Arrangements of Repetitive Elements in the C57BL/6J Mouse Genome Implicating Their Functional Roles

Young-Kwan Lee, Kang-Hoon Lee, Seon-Gyu Kim, Ramzi Melhem, Chang-Suk Moon, Sicong Liu, David G. Greenhalgh, Kiho Cho


Perioperative Chemotherapy in Gastroesophageal Cancer. A Retrospective Monocenter Evaluation of 42 Cases

Ann-Christin E. Brehler, Wolfgang Hartmann, Stefanie Wiebe, Andrea Kerkhoff, Christoph Schliemann, Daniel Palmes, Norbert Senninger, Frank Lenze, Hansjoerg Ullerich, Wolfgang E. Berdel, Torsten Kessler


An AUG Codon Conserved for Protein Function Rather than Translational Initiation: The Story of the Protein sElk1

Noemie Legrand, Tanguy Araud, Beatrice Conne, Odin Kuijpers, Pascale Jaquier-Gubler, Joseph Curran


Added Value of Arterial Enhancement Fraction Color Maps for the Characterization of Small Hepatic Low-Attenuating Lesions in Patients with Colorectal Cancer

Mina Park, Yong Eun Chung, Kyung Ah Kim, Woo-Suk Chung, Hye Sun Lee, Kyung Hwa Han, Myeong-Jin Kim, Ki Whang Kim


Translational Initiation at a Non-AUG Start Codon for Human and Mouse Negative Elongation Factor-B

Haihui Pan, Xiayan Zhao, Xiaowen Zhang, Mohamed Abouelsoud, Jianlong Sun, Craig April, Asma Amleh, Jian-Bing Fan, Yanfen Hu, Rong Li


Strain Differences in Fitness of Escherichia coli O157:H7 to Resist Protozoan Predation and Survival in Soil

Subbarao V. Ravva, Chester Z. Sarreal, Robert E. Mandrell


PML Nuclear Bodies and SATB1 Are Associated with HLA Class I Expression in EBV+ Hodgkin Lymphoma

Yuxuan Liu, Anke van den Berg, Rianne Veenstra, Bea Rutgers, Ilja Nolte, Gustaaf van Imhoff, Lydia Visser, Arjan Diepstra


Robust Metabolic Responses to Varied Carbon Sources in Natural and Laboratory Strains of Saccharomyces cerevisiae


Health Behaviors of Korean Gastric Cancer Survivors with Hypertension: A Propensity Analysis of KNHANES III-V (2005–2012)

So-Ra Jo, Ju-Youn Joh, Ju-Ri Jeong, Sun Kim, Yeon-Pyo Kim


Protein NMR Structures Refined without NOE Data

Hyojung Ryu, Tae-Rae Kim, SeonJoo Ahn, Sunyoung Ji, Jinhyuk Lee


Role of Polypyrimidine Tract Binding Protein in Mediating Internal Initiation of Translation of Interferon Regulatory Factor 2 RNA

Debojyoti Dhar, Musturi Venkataramana, Anand Ponnuswamy, Saumitra Das


Predicting Inter-Species Cross-Talk in Two-Component Signalling Systems

Sonja Pawelczyk, Kathryn A. Scott, Rebecca Hamer, Gareth Blades, Charlotte M. Deane, George H. Wadhams


Comparative Transcriptional Analysis Reveals Differential Gene Expression between Asymmetric and Symmetric Zygotic Divisions in Tobacco


Luminance, Colour, Viewpoint and Border Enhanced Disparity Energy Model

Jaime A. Martins, João M. F. Rodrigues, Hans du Buf


Spectral Distance Between Graphs and the Energy-Based Controllability of Networks

Institute of Electrical and Electronics Engineers (IEEE)

Department of Electrical Engineering, The University of Texas at Dallas, Richardson, TX, USA


ALTITUDINAL VARIATION IN HAWAIIAN METROSIDEROS

Department of Botany University of Hawaii  Honolulu

Abstract: Hawaiian Metrosideros is a highly polymorphic complex that is distributed throughout the six major islands of the Hawaiian Island chain from tropical climates near sea level to altitudes up to 8,500 ft with frost. Its populations extend continuously over many areas with average annual precipitation ranging from 30 to 450 in. and with diverse edaphic and topographical features. The Hawaiian forms are probably all derived from one or a very small number of ancestral introductions that arrived within the last 20 million years by longdistance dispersal. Seeds collected from diverse altitudinal sites on the islands of Hawaii and Maui and grown under uniform greenhouse conditions at Honolulu show evidence of ecotypic differentiation along altitudinal gradients. Seedlings from these islands separated by 50 miles of ocean show parallelism in their altitudinal differentiation in plant height and leaf size, but with strongly overlapping variation from site to site.


Role of CdTe Interface Structure on CdS/CdTe Photovoltaic Device Performance

Niva K. Jayswal, Dipendra Adhikari, Indra Subedi, Ambalanath Shan, Nikolas J. Podraza

Department of Physics and Astronomy, Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo, OH 43606, USA

National Science Foundation (NSF), National Science Foundation (NSF), Air Force Research Laboratory, Air Force Research Laboratory

Abstract: Glancing angle deposition (GLAD) of CdTe can produce a cubic, hexagonal, or mixed phase crystal structure depending upon the oblique deposition angles (Φ) and substrate temperature. GLAD CdTe films are prepared at different Φ at room temperature (RT) and a high temperature (HT) of 250 °C and used as interlayers between the n-type hexagonal CdS window layer and the p-type cubic CdTe absorber layer to investigate the role of interfacial tailoring at the CdS/CdTe heterojunction in photovoltaic (PV) device performance. The Φ = 80° RT GLAD CdTe interlayer and CdS both have the hexagonal structure, which reduces lattice mismatch at the CdS/CdTe interface and improves electronic quality at the heterojunction for device performance optimization. The device performance of HT CdS/CdTe solar cells with Φ = 80° RT with 50 to 350 nm thick GLAD CdTe interlayers is evaluated in which a 250 nm interlayer device shows the best device performance with a 0.53 V increase in open-circuit voltage and fill-factor product and a 0.73% increase in absolute efficiency compared to the HT baseline PV device without an interlayer.


Derivatives of compound matrix valued functions

Journal of Mathematical Analysis and Applications

National Science Foundation, Office of Naval Research, National Science Foundation, Office of Naval Research