38 research outputs found
HIV Protein Sequence Hotspots for Crosstalk with Host Hub Proteins
- Author
- A Greenway
- A Henschel
- AC Vendel
- AK Dunker
- Aydin Tozeren
- B Ackerson
- CL Ruegg
- CM Gould
- D Ekman
- Denis Dupuy
- DR Borger
- EE Hill
- EF Pettersen
- F Cardarelli
- F Diella
- F Meggio
- F Meggio
- G Baier-Bitterlich
- H Jian
- H Li
- H Wang
- HM Berman
- HM Craig
- J Friborg
- JE Dickerson
- K Harada
- K Kadaveru
- K Saksela
- KV Prasad
- L Deng
- M Hiipakka
- M Matsubara
- M Schindler
- MA Dimattia
- MA Perez
- Mahdi Sarmady
- MD Dyer
- MR Schaefer
- N Arhel
- NE Davey
- NE Davey
- O Haffar
- O Tastan
- O Tastan
- P Abada
- P Bayer
- P Beauparlant
- P Evans
- P Evans
- RJ Edwards
- S Balakrishnan
- S Betzi
- S Grzesiek
- S Sei
- SH Tan
- SK Srinivas
- SS Chen
- T Ammosova
- T Kino
- TH Tahirov
- TS Keshava Prasad
- V Neduva
- V Neduva
- W Fu
- W Radding
- William Dampier
- X Yang
- X Yang
- Y He
- Y Liu
- Z Nie
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2011
- Field of study
HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2). We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes
Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome
- Author
- A Asokan
- A Bayes
- A Burgess
- A Wistuba
- AA Scheel
- AM Tintaru
- B Akache
- BR Martin
- C Holscher
- C Naro
- C Pan
- C Summerford
- CA Schreiber
- CF Valori
- CT Chang
- CY Yu
- DM McCarty
- EB Lee
- G Murlidharan
- GS Arnold
- H Buning
- J Chu
- J Cox
- J Cox
- J Du
- J Qiu
- J Rappsilber
- JL Ronan
- JS Johnson
- K Varadi
- KD Foust
- KH Warrington Jr
- L Geng
- L Lisowski
- L Shkreta
- M Akerman
- M Hohl
- M Mano
- M Mielcarek
- M Monici
- MA DiMattia
- MA Kotterman
- MD Stachler
- N Déglon
- N Majdzadeh
- P Wu
- R Weigert
- RB Tunnicliffe
- RD Dayton
- RE Kelemen
- S Michelfelder
- S Shen
- SA Nicklin
- SJ Gray
- SR Adams
- T Kashima
- T Okada
- TA Bolger
- TW Loo
- V Basile
- W Fischle
- X Li
- Y Liu
- Y Zheng
- YS Tseng
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/11/2017
- Field of study
Adeno-associated viruses (AAVs) are attractive gene therapy vectors due to their low toxicity, high stability, and rare integration into the host genome. Expressing ligands on the viral capsid can re-target AAVs to new cell types, but limited sites have been identified on the capsid that tolerate a peptide insertion. Here, we incorporated a site-specific tetracysteine sequence into the AAV serotype 9 (AAV9) capsid, to permit labelling of viral particles with either a fluorescent dye or biotin. We demonstrate that fluorescently labelled particles are detectable in vitro, and explore the utility of the method in vivo in mice with time-lapse imaging. We exploit the biotinylated viral particles to generate two distinct AAV interactomes, and identify several functional classes of proteins that are highly represented: actin/cytoskeletal protein binding, RNA binding, RNA splicing/processing, chromatin modifying, intracellular trafficking and RNA transport proteins. To examine the biological relevance of the capsid interactome, we modulated the expression of two proteins from the interactomes prior to AAV transduction. Blocking integrin αVβ6 receptor function reduced AAV9 transduction, while reducing histone deacetylase 4 (HDAC4) expression enhanced AAV transduction. Our method demonstrates a strategy for inserting motifs into the AAV capsid without compromising viral titer or infectivity
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
- Author
- A Abbate
- A Abhyankar
- A Adams
- A Agafina
- A Akyea-Djamson
- A Alan
- A Alfieri
- A Alfrey
- A Alvarisqueta
- A Amos
- A Anadiotis
- A Anneveldt
- A Antolick
- A Arthur
- A Aslam
- Abaci F
- Abdullakutty J
- Abhaichand R
- Abib E Jr
- Aboufakher R
- Abrantes J
- Abreu M
- Abulencia K
- Acampora D
- Acampora M
- Accini Mendoza Jl
- Aceto L
- Acevedo B
- Acevedo L
- Acheatel R
- Actis Mv
- Adams M
- Adjic Nc
- Affaki Gs
- Agarwal Dk
- Aggarwal Rk
- Agosta Gf
- Aguilar M
- Aguilar M
- Ahire N
- Ahmad I
- Ahmed Sh
- Ahn Y
- Aish B
- Aiub F
- Aiub J
- Ajax K
- Ajioka M
- Akai Y
- Akatova E
- Akrap B
- Al Joundi T
- Al-Khalili F
- Albisu J
- Alcalde Jm
- Alcide P
- Alfonso T
- Allen J
- Alllison Dc
- Almaliky T
- Amerena J
- Andersen K
- Andor M
- Angelova I
- Angiolillo D
- Anita S
- Anker Sd
- Antalik L
- Antonicelli R
- Aparicio Cv
- Apel T
- Apostolovic S
- Ara M
- Aragorn L
- Arango Jl
- Araujo Fonseca M
- Ardissino D
- Arenas Leon Jl
- Arevalo S
- Argiolas G
- Arif I
- Armas E
- Aron G
- Arora S
- Asafu-Adjaye N
- Ashcom T
- Ashford M
- Ashino K
- Asim Oktay Ao
- Assarsson E
- Ata B
- Ather N
- Atieh M
- Aull L
- Avalos V
- Avdonina N
- Awasthi Ak
- Axthelm C
- Ayala M
- Ayasse D
- Ayasse M
- Azizad M
- Azize Gm
- B Becker
- Baar M
- Babu R
- Backer T
- Badea C
- Baden M
- Baehl S
- Baek C
- Baeumer A
- Bagi Es
- Bai A
- Bailey K
- Bailey S
- Bair S
- Baker A
- Baker C
- Bakhai A
- Bakker H
- Baksi A
- Baldin Mg
- Bali Hk
- Ballantyne C
- Ballmajo M
- Balode A
- Balukova E
- Bang Sa
- Banker D
- Banker K
- Baquero A
- Barbarash Ol
- Barbato E
- Barbosa E
- Barnett S
- Baron S
- Barreto M
- Barroso A
- Barroso W
- Bartkowiak A
- Bartosh L
- Bartuseviciene S
- Bashir K
- Baszak J
- Bata Ir
- Bayram E
- Beall K
- Beaudry M
- Beauregard La
- Beckett L
- Belejchak P
- Belle Isle J
- Belohlavek J
- Bendelow T
- Bender D
- Benedetti G
- Benjamin S
- Benton J
- Berdoff R
- Berger V
- Bergeron P
- Bergholtz T
- Bergler-Klein J
- Berk M
- Berli Ma
- Bernstein M
- Berra Fc
- Berti S
- Berulfsen A
- Bevilacqua Mt
- Bhadade S
- Bilazarian S
- Bilodeau N
- Binder A
- Binns Y
- Birdane A
- Bisne V
- Bitzer V
- Blagdon M
- Blahey M
- Blankenberg S
- Blazsek Z
- Bloch S
- Blom Kb
- Bluemel J
- Blumberg C
- Blumenthal R
- Bocanera M
- Bodanese L
- Boffetti P
- Bohra P
- Bohula E
- Boivin Mc
- Bolduc H
- Boley K
- Bolognesi Mg
- Bolsmann C
- Boman K
- Bonner J
- Borrayo Na
- Boström På
- Botelho R
- Botta C
- Boudreaux R
- Boulanger K
- Bourgeois S
- Bouvy C
- Bowen L
- Boyarkin M
- Bradley A
- Brady L
- Bramlet D
- Brath H
- Braun P
- Bredlau C
- Brickman T
- Briggs S
- Briké C
- Brodmann M
- Brons S
- Brousalis L
- Brouwer M
- Brown C
- Brown N
- Brown S
- Buchannan C
- Budaj A
- Budassi N
- Budkova J
- Bugan V
- Buhlman S
- Bulashova O
- Bunschoten P
- Burke W
- Burley T
- Burova N
- Burris H
- Burton C
- Burton J
- Burton M
- Burtt D
- Busak L
- Busic N
- Byars W
- Bøen Rh
- C Clavier-Firmin
- C Conradie
- C Contzen
- C Cotes
- C Covert
- C Cuneo
- Caballero-Valiente B
- Cabau Jr
- Calabrese A
- Campanale Eg
- Candusso R
- Cantor W
- CANTOS Trial Group. Krum H
- Capova L
- Carabajal T
- Carr K
- Carrillo J
- Caruso G
- Casala J
- Caso P
- Casoinic F
- Castillo J
- Castillo T
- Cech V
- Cei L
- Cendali G
- Cepinskiene L
- Cerda L
- Cermak O
- Chachalis G
- Chaggar S
- Chambers J
- Chamblee T
- Chang K
- Chang Kc
- Chang Wh
- Charlier F
- Charmarthi B
- Chattin W
- Chauhan D
- Chauhan H
- Chaussé I
- Chavada J
- Chaverra I
- Chaware G
- Chee L
- Chella S
- Chen Cp
- Chen J
- Chen Mh
- Chen Y
- Chen Yc
- Chen Zc
- Cheng Jj
- Cheng S
- Cheng Sm
- Cherlin R
- Cheung D
- Chhabra A
- Chintala P
- Chiodi L
- Choi Aj
- Chou S
- Chouinard G
- Christensen L
- Christenson S
- Chung A
- Churina S
- Cifkova R
- Ciglenecki N
- Cioffi A
- Cislowski D
- Cleveland T
- Clocotan M
- Cmrecnjak J
- Colfer H
- Colhoun H
- Collier D
- Collins R
- Coloma G
- Colquhoun D
- Colvin T
- Coman S
- Commerford P
- Commerford P
- Conrado Y
- Cools F
- Cornel Jh
- Corona V
- Coronel J
- Cosgrove N
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- Costa Amorim R
- Coufalova Z
- Covell W
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- Crandall L
- Crawford G
- Crea F
- Crepps K
- Crocamo A
- Cromer M
- Cruz H
- Cruz H
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- Csala L
- Cucher F
- Cuentas I
- Cuervo A
- Curiac D
- Cymerman K
- Cyprian R
- Czerski T
- D'Amours Dg
- D Dash
- D Dattani
- D Denham
- D Desai
- D Desalle
- D Digangi
- D Dunn
- Da Costa F
- Da Silva A
- Da Silva D Jr
- Da Silva O Jr
- Dahlen G
- Dalseg Am
- Damron M
- Danik J
- Davalos C
- Dave B
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- Davidsson K
- Davies M
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- Davis B
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- Dawkins-Hughes S
- Dawood Sy
- Dayer M
- De Boer P
- De Caterina R
- De Jong C
- De Knijf K
- De Krumbach L
- De Los Milagros Had M
- De Los Rios M
- De Rosa S
- De Vos A
- De Wolf L
- Dean J
- Debnam S
- Decsi K
- Decsi Kl
- Dedek V
- Dedkova S
- Defosse C
- Degennaro N
- Dehning M
- Dela Llana A
- Delfonso F
- Delforge M
- Delgadillo T
- Dellasa M
- Dellborg M
- Dellorso M
- Demidova M
- Den Hartog F
- Denecke C
- Dengler T
- Dermitzakis A
- Deslongchamps F
- Dessalvi Cc
- Destro M
- Dettmer M
- Devasia T
- Deweerdt N
- Dhanak R
- Dhawan M
- Di Biase M
- Diago M
- Diaz M
- Dicken T
- Dickstein K
- Diederich C
- Diederich M
- Diehl R
- Diller P
- Dimattia M
- Dimitrov G
- Diodati J
- Dobariya H
- Dobilas V
- Dodds G
- Doesborg L
- Doggett J
- Dognini Gp
- Doi M
- Dokupilova A
- Dommerholt R
- Donahue K
- Donath M
- Donaubauer T
- Dong X
- Dormidontova G
- Dorogova I
- Dos Santos A
- Dos Santos F
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- Doughty A
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- Dovgalevskiy Y
- Dovgolis S
- Dragutksy B
- Dreese M
- Drost I
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- Genest J
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- Gotcheva N
- Goudev A
- Gould R
- Govindaraj D
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- Gralow J
- Gravellone M
- Gravenhorst-Muenter U
- Green E
- Greener R
- Greenway F
- Grieshaber V
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- Grigaraviciene I
- Grigorova V
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- Grosse A
- Grover A
- Grundtvig M
- Gudipati Rvc
- Guerrero A
- Guillinta P
- Gundala Ak
- Gupta A
- Gupta A
- Gupta M
- Gupta V
- Gutmann J
- Guzman I
- Guzman P
- Gwyn M
- Gyorgyova E
- H Haldane
- H Hansen
- H Haught
- H Hill
- Haase F
- Haege R
- Haenel T
- Hage F
- Hageman T
- Hagemann D
- Hagenow A
- Hagiwara Y
- Haidar A
- Haider K
- Hakas J
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- Halliwell Tc
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- Hansson A
- Hanustiakova A
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- Hardas S
- Hardee L
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- Hartleib M
- Hartwell J
- Hasan F
- Hasbani E
- Hasegawa K
- Hattler B
- Haughton G
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- Hegedus V
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- Hosokawa S
- Hotchkiss D
- Houra M
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- Hsieh Ic
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- Humbert J
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- Hutchens E
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- Hwang Jj
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- Iijima T
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- Imbrognio M
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- Jaguszewska G
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- Kabakchieva Vm
- Kaczmarek N
- Kafarakis P
- Kaiserova L
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- Kala P
- Kaldara E
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- Kamensky G
- Kamiya H
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- Kanitz S
- Kapp I
- Kara Yd
- Karakai H
- Karel I
- Karpuram M
- Karsai Xz
- Kastelein Jjp
- Kataoka M
- Katona A
- Katova T
- Kaur H
- Kawahara M
- Kawai M
- Kawasaki T
- Kawka-Urbanek T
- Kazanskay E
- Ke Y
- Keba E
- Keenan S
- Kelehan S
- Kellnerova I
- Kelly R
- Kelt T
- Kendall T
- Kereiakes D
- Khan A
- Khan M
- Khan R
- Khan S
- Khariouzov A
- Khirmanov V
- Khromtsova O
- Kick J
- Kiefer R
- Kietselaer B
- Kim B
- Kim Ks
- Kim M
- Kimmel M
- King A
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- Kirkland S
- Kiss Rg
- Kissel S
- Kitchens D
- Klamm M
- Klein C
- Klein P
- Klemsdal To
- Kleve R
- Klugherz B
- Knight J
- Knutsson A
- Koba M
- Kobalava Z
- Kodem Dr
- Koeitti P
- Koenig W
- Kojima E
- Kok M
- Koldas N
- Koleckar P
- Kolikova V
- Kolleroy C
- Kolokathis F
- Komati S
- Komura Y
- Kondagunta V
- Konradi A
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- Kopczyńska M
- Korban E
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- Kormann A
- Korte M
- Korth-Wiemann B
- Kose V
- Kosmacheva E
- Kostakou P
- Kostis J
- Kotek L
- Kouz Sm
- Kovacic D
- Kovacs A
- Kozak M
- Kozlova S
- Krapivsky A
- Kreckova M
- Kreutter F
- Krupciakova B
- Krupicka J
- Kuenzler J
- Kulibaba E
- Kulkarni L
- Kullal P
- Kultursay H
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- Kumbla M
- Kuntzsch A
- Kuo Jy
- Kuramochi T
- Kuruma T
- Kusnick B
- Kuzin A
- Kyo E
- L Levinson
- L Lim
- L Link
- L Liu
- Laane E
- Labovitz R
- Lachance P
- Lai Wt
- Lail J
- Lainscak M
- Lake J
- Lal S
- Lamance J
- Lamas G
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- Lambert J
- Lameira A
- Lamontagne C
- Landers B
- Landolfi A
- Landzberg J
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- Zineldine A.
- Zirlik A
- Zucchetti C
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Similarities between human and animal spatial memory: Item and order information
- Author
- A. A. Wright
- A. A. Wright
- A. Drewnowski
- A. F. Healy
- A. F. Healy
- B. B. Murdock
- B. B. Murdock
- B. B. Murdock
- B. B. Murdock
- B. V. DiMattia
- D. B. Berch
- D. Bartram
- D. Gaffan
- D. McNicol
- D. S. Olton
- E. H. Cornell
- E. M. MacPhail
- G. E. Weaver
- G. Loftus
- H. C. Santiago
- H. G. Shulman
- J. C. Jahnke
- J. M. Neale
- K. A. Haig
- K. Pezdek
- L. Hasher
- L.-G. Nilsson
- M. C. Corballis
- M. Glanzer
- M. J. Hacker
- O. J. L. Tzeng
- P. Muter
- R. C. Atkinson
- R. E. Fitzgerald
- R. G. Crowder
- R. K. R. Thompson
- R. P. Kesner
- R. P. Kesner
- R. T. Zacks
- S. B. Yntema
- S. C. Hirtle
- S. F. Sands
- S. Grossberg
- W. A. Phillips
- W. A. Roberts
- W. A. Roberts
- W. A. Roberts
- W. Donaldson
- W. S. Maki
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
ATLAS detector and physics performance: Technical Design Report, 1
- Author
- Abdinov O.B.
- Abolins M.
- Abramowicz H.
- Acerbi E.
- Ackermann K.
- Ackers M.
- Aderholz M.
- Ahlen S.
- Aielli G.
- Airapetian A.
- Akerman D.
- Akesson T.
- Akhmedov A.
- Akhoundov A.
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- Alam S.
- Aleksa M.
- Aleppo M.
- Alessandria F.
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- Alexander G.
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- Allport P.P.
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- Ambrosini G.
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- Ammosov V.V.
- Amorim A.
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- Andrieux M.L.
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- Publication venue
- Union of Concerned Scientists
- Publication date
- 01/01/1999
- Field of study
Correspondence between rats and humans in the utilization of retrospective and prospective codes
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
What's So Special About Special Libraries?
- Author
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
Rats remember not wisely but too well
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Rats do show primacy and recency effects in memory for lists of spatial locations: A reply to Gaffan
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Primacy, recency, and the variability of data in studies of animals’ working memory
- Author
- A. A. Wright
- A. A. Wright
- A. A. Wright
- A. A. Wright
- B. V. DiMattia
- B. V. DiMattia
- C. P. Shimp
- D. G. Mumby
- D. Gaffan
- D. Gaffan
- D. Gaffan
- E. A. Murray
- E. M. Macphail
- G. J. Hitch
- G. J. Hitch
- H. C. Santiago
- J. Cohen
- J. J. Bolhuis
- J. P. Aggleton
- J. P. Buchanan
- L. A. Rothblat
- M. B. Moss
- P. Reed
- R. G. Cook
- R. G. O’Brien
- R. H. I. Dale
- R. K. R. Thompson
- R. P. Kesner
- R. P. Kesner
- R. P. Kesner
- R. P. Kesner
- R. P. Kesner
- R. P. Kesner
- R. P. Kesner
- R. P. Kesner
- S. R. Sands
- S. Roberts
- W. A. Roberts
- W. A. Roberts
- W. A. Roberts
- W. H. Overman
- W. L. Hays
- W. S. Maki
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study