Artigos de revistas: "Jake"

1

Andracki, Thaddeus. "Just Jake by Jake Marcionette". Bulletin of the Center for Children's Books 67, n.º 7 (2014): 366–67. http://dx.doi.org/10.1353/bcc.2014.0183.

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Chudnov, Daniel, Cynthia Crooker e Kimberly Parker. "jake". Serials Review 26, n.º 4 (dezembro de 2000): 12–17. http://dx.doi.org/10.1080/00987913.2000.10764619.

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Major, Genée Ciurus. "Everything’s Jake". English Journal 107, n.º 2 (1 de novembro de 2017): 31–34. http://dx.doi.org/10.58680/ej201729352.

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This article explores the compassion created when students ask essential questions about life and death. The author describes her personal journey with her students as they experience what it means to be human.

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Gonzalez-Traves, P., B. Murray, F. Campigotto, A. Meng e J. A. DI Paolo. "THU0067 JAK SELECTIVITY AND THE IMPACT ON CYTOKINE SIGNALING INHIBITION AT CLINICAL RHEUMATOID ARTHRITIS DOSES". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 246.1–246. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2074.

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Background:Janus kinase 1 (JAK1) inhibitors are efficacious in rheumatoid arthritis (RA). Despite having similar efficacy, in vitro studies have shown differences in JAK selectivity profiles for the small-molecule JAK inhibitors (JAKi) baricitinib (BARI), tofacitinib (TOFA), and upadacitinib (UPA).1For example, BARI and UPA are JAK1/JAK2 selective, while TOFA is JAK1/JAK3 selective, but each JAKi has some activity against other JAKs. As JAKs form signaling pairs, differences in selectivity could lead to distinct pharmacologic profiles that may impact clinical efficacy and safety.Objectives:As a first step to understand the basis of potential differences at therapeutic doses, we compared the selectivity and potency of filgotinib (FIL) and its major metabolite (MET) to those of BARI, TOFA, and UPA in cytokine-stimulated peripheral blood mononuclear cells (PBMCs) and whole blood (WB).Methods:PBMCs and WB from healthy donors were incubated in vitro with 8 doses of each JAKi, and levels of signal transducer and activator of transcription phosphorylation (pSTAT) were measured following cytokine stimulation. Half maximal inhibitory concentration (IC50) values were calculated in phenotypically sorted leukocyte populations by flow cytometry. Therapeutic dose relevance of the in vitro analyses was assessed using calculated mean concentration-time profiles from JAKi population pharmacokinetic data in RA subjects. For each JAKi, the time above IC50and average daily pSTAT inhibition were calculated for each cytokine/STAT pair in B cells, CD4+ T cells, CD8+ T cells, monocytes, and/or NK cells.Results:Cellular assays in PBMCs and WB showed dose-dependent inhibition of cytokine-induced pSTATs with all JAKi (correlation between the protein-adjusted IC50values from PBMCs and IC50values from WB, r2=0.98). Among the most potently inhibited pathways were JAK1/TYK2-dependent cytokine, interferon alpha (IFNα), and the JAK1/2-dependent cytokine, interleukin (IL)-6. FIL and MET had weaker potencies against JAK2/TYK2 (G-CSF/pSTAT3), JAK1/2 (IFNƴ/pSTAT1), and JAK2/2 (granulocyte-macrophage colony-stimulating factor [GM-CSF])-dependent pathways compared to JAK1/TYK2 (IFNα/pSTAT5). FIL and MET showed the greatest selectivity vs the JAK2/2 pathway (GM-CSF/pSTAT3) in monocytes.The mean concentration-time profiles and time above IC50over 24 hr for each cytokine/STAT pathway showed that JAK1/2 (IL-6/pSTAT1) and JAK1/TYK2 (IFNα/pSTAT1) pathways were strongly modulated with all tested JAKi. FIL (200 mg) showed similar activity in average target coverage and time above IC50to the approved low doses of TOFA (5 mg) and UPA (15 mg); conversely, FIL had reduced mean average inhibition and time above IC50levels against JAK1/2 (IFNƴ/pSTAT1), JAK1/3-dependent cytokines (IL-2, -4, and -15), JAK2/TYK2 (G-CSF/pSTAT3), and JAK2/2 (GM-CSF/pSTAT5)-dependent pathways compared to TOFA and UPA, and in certain cases to BARI (2 mg).Conclusion:Different JAKi modulate distinct cytokine pathways to varying degrees, and no agent potently and continuously inhibited an individual cytokine signaling pathway throughout the dosing interval. FIL (200 mg) showed a similar inhibition profile to TOFA, BARI, and UPA against the JAK1/TYK2- (IFNα/pSTAT1) or JAK1/2-dependent (IL-6/pSTAT1) responses, consistent with the role of these pathways in clinical efficacy.2However, FIL displayed a differentiated pharmacologic profile from the other JAKi, showing biologically reduced activity on the JAK1/2 (IFNγ)-, JAK1/3 (IL-2, -4 and -15)-, JAK2/TYK2 (G-CSF)-, and JAK2/2 (GM-CSF)-dependent pathways, which play important roles in hematopoiesis and immune function. These data suggest that FIL (200 mg) may have less impact on a subset of homeostatic immune functions signaling via JAK2 and JAK3 than those observed at the clinically approved doses of TOFA (5 mg and 10 mg), UPA (15 mg), and BARI (4 mg).References:[1]McInnes IB, et al. Arthritis Res Ther. 2019;21:183.[2]Banerjee S, et al. Drugs. 2017;77:521-546.Disclosure of Interests:Paqui Gonzalez-Traves Employee of: Gilead, Bernard Murray Employee of: Gilead, Federico Campigotto Employee of: Gilead, Amy Meng Shareholder of: Gilead Sciences, Employee of: Gilead, Julie A. Di Paolo Employee of: Gilead

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Spaner, D., M. Iqbal, A. Navabi, K. Strenzke e B. Beres. "Jake hard red spring wheat". Canadian Journal of Plant Science 100, n.º 1 (1 de fevereiro de 2020): 129–35. http://dx.doi.org/10.1139/cjps-2019-0130.

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Jake hard red spring wheat (Triticum aestivum L.) was developed using a modified bulk breeding method at the University of Alberta, Edmonton, AB. Jake is an awned, hollow-stemmed line with high yield potential, medium tall plants, and medium maturity. During the three years (2015–2017) of evaluation in the Parkland Wheat Cooperative test, Jake yielded 6% higher than the mean of all of the checks, and matured 0.7 and 1.7 d later than Parata and Splendor but 2.9 d earlier than Glenn. Jake was 91.2 cm tall, shorter than AC Splendor (95.8 cm), but similar in height to Glenn (91.8 cm) and Parata (92 cm). The lodging score of Jake (2.2) was lower than Parata (3.1) and AC Splendor (3.1), but similar to Glenn. The test weight of Jake (80.8) was higher than AC Splendor (78.3), similar to Parata (80.5), but lower than Glenn (82.5). The grain weight of Jake (35.6 g) was similar to Parata (35.6 g), but lower than Glenn (36.7 g) and AC Splendor (37.4 g), while the NIR Protein of Jake (15.9%) was higher than Glenn (15.5%) and similar to the other checks. Jake was moderately resistant to resistant to leaf, stem, and stripe rusts, and moderately resistant to common bunt during the 3 yr of testing. The reaction of Jake to Fusarium head blight was variable and ranged from moderately susceptible to moderately resistant, with DON values similar to Carberry and Glenn. Three years of end-use quality evaluation has indicated that Jake is acceptable for the CWRS class.

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6

Nina Notman, special to C&EN. "Jacob “Jake” Eichhorn". C&EN Global Enterprise 100, n.º 29 (22 de agosto de 2022): 26. http://dx.doi.org/10.1021/cen-10029-obits3.

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7

MacDonald, Douglas. "Portrait of Jake". American Journal of Hospice and Palliative Medicine® 18, n.º 4 (julho de 2001): 283–85. http://dx.doi.org/10.1177/104990910101800416.

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8

Weiss, Jillian. "Awakening to Jake". Missouri Review 41, n.º 4 (2018): 116–33. http://dx.doi.org/10.1353/mis.2018.0050.

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9

Scaife, B. "John ("Jake") Stohlner". BMJ 324, n.º 7352 (22 de junho de 2002): 1527e—1527. http://dx.doi.org/10.1136/bmj.324.7352.1527/e.

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10

Deverell, William, e Tom Sitton. "Forget it, Jake". Boom 3, n.º 3 (2013): 3–7. http://dx.doi.org/10.1525/boom.2013.3.3.3.

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This article places the 1974 film Chinatown alongside the historical events that the film portrays. Rather than a simple comparison between fact and fiction, Deverell and Sitton instead explore what we can learn about the people, places, and events in both Chinatown and the history of the Los Angeles aqueduct.

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Lees, J. A., P. R. Bown e J. R. Young. "Jake Hancock: reminiscences". Proceedings of the Geologists' Association 117, n.º 2 (janeiro de 2006): 125–27. http://dx.doi.org/10.1016/s0016-7878(06)80004-0.

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12

Brent Chesley. "Jake, It's Chinatown". Fourth Genre: Explorations in Nonfiction 4, n.º 1 (2002): 172–82. http://dx.doi.org/10.1353/fge.2013.0071.

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13

Kennedy, W. J. "Jake Hancock 1928–2004". Mineralogical Magazine 68, n.º 4 (agosto de 2004): 712–13. http://dx.doi.org/10.1180/s0026461x00041815.

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14

Silver, Joel. "EXIT INTERVIEW: JAKE CHERNOFSKY". RBM: A Journal of Rare Books, Manuscripts, and Cultural Heritage 1, n.º 1 (1 de março de 2000): 77–82. http://dx.doi.org/10.5860/rbm.1.1.182.

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Jacob L. (“Jake”) Chernofsky recently retired from his position of editor and publisher of AB Bookman’s Weekly magazine, which he joined in 1973. AB, which was originally titled Antiquarian Bookman, was founded on January 3, 1948 by Sol. Malkin, and the magazine’s name was changed to AB Bookman’s Weekly in 1967, “in recognition of a readership comprising mostly specialist dealers.” AB, which had been widely read for several decades by people involved in the world of antiquarian books, suspended publication in December 1999. How did you get involved in antiquarian books and AB? I got involved in antiquarian books through . . .

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15

Sullivan, Jake. "Remarks by Jake Sullivan". Proceedings of the ASIL Annual Meeting 109 (2015): 341–42. http://dx.doi.org/10.5305/procannmeetasil.109.2015.0341a.

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16

Shannon, J. G., J. A. Wrather, D. A. Sleper, R. T. Robbins, H. T. Nguyen e S. C. Anand. "Registration of ‘Jake’ Soybean". Journal of Plant Registrations 1, n.º 1 (maio de 2007): 29–30. http://dx.doi.org/10.3198/jpr2006.05.0347crc.

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17

Tacchi, Derek. "James (“Jake”) Knox Russell". BMJ 334, n.º 7594 (22 de março de 2007): 643.5–643. http://dx.doi.org/10.1136/bmj.39155.563796.be.

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18

Spisak, April. "Nightfall by Jake Halpern". Bulletin of the Center for Children's Books 69, n.º 4 (2015): 200. http://dx.doi.org/10.1353/bcc.2015.0914.

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19

Doḡu, Hikmet. "BREAKFAST SPECIAL. Jake Tilson". Art Documentation: Journal of the Art Libraries Society of North America 9, n.º 3 (outubro de 1990): 151. http://dx.doi.org/10.1086/adx.9.3.27948246.

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20

Sponsel, Valerie. "Jake MacMillan (1924–2014)". Phytochemistry 115 (julho de 2015): 271–72. http://dx.doi.org/10.1016/j.phytochem.2014.11.001.

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Batten, David J., e Jim Kennedy. "Jake Hancock: an appreciation". Cretaceous Research 25, n.º 4 (agosto de 2004): 435–37. http://dx.doi.org/10.1016/j.cretres.2004.06.001.

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22

Anderson, Donna S., John H. Melby e James L. Folcik. "A Short History of the “Jake” Niobrara Horizontal Oil Discovery, Weld County, Colorado". Mountain Geologist 52, n.º 3 (1 de julho de 2015): 5–12. http://dx.doi.org/10.31582/rmag.mg.52.3.5.

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In late 2009, the EOG Resources Jake 2-01H horizontal well (Sec. 1, T11N, R63W, Weld County, CO) re-opened the Niobrara oil play in the DJ basin. The play for EOG was built on comprehensive geologic scrutiny across the entire DJ basin of Colorado and Wyoming. Niobrara tests in the original Hereford field, four miles east of the Jake discovery, had bypassed Niobrara pay. This data, along with a 1991-vintage horizontal well with a vertical core through the Niobrara B Chalk in the original Hereford field, set up the prospect around the Jake discovery. A proprietary 40 square-mile 3-D seismic survey acquired and processed between May and July 2009 provided data for well-location planning. Determination of current-day maximum horizontal stress of N55°E in the Lamotta 5-01M monitoring well led to the drilling of the Jake 2-01H, although the Jake well was not the original planned location for the first horizontal test in the prospect area. Since the Jake discovery, EOG has drilled 71 Niobrara horizontal wells in Hereford field, and industry has drilled more than 4400 horizontal wells in the entire DJ basin Niobrara play.

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23

Spisak, April. "The Well by Jake Wyatt". Bulletin of the Center for Children's Books 75, n.º 7 (2022): 235. http://dx.doi.org/10.1353/bcc.2022.0151.

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24

Shankar, Guha. "Discovering Rastafari! by Jake Homiak". American Anthropologist 113, n.º 3 (24 de agosto de 2011): 508–9. http://dx.doi.org/10.1111/j.1548-1433.2011.01363.x.

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25

Silverstone, Daniel, e Joe Whittle. "‘Forget it, Jake. It’s Chinatown’". Police Journal: Theory, Practice and Principles 89, n.º 1 (26 de fevereiro de 2016): 70–84. http://dx.doi.org/10.1177/0032258x16631566.

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26

Ebright, Ryan. "Moby-Dick by Jake Heggie". Notes 71, n.º 1 (2014): 140–41. http://dx.doi.org/10.1353/not.2014.0102.

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27

Epp, Jake. "Address: The Honourable Jake Epp". Health Promotion International 1, n.º 4 (1986): 413–17. http://dx.doi.org/10.1093/heapro/1.4.413.

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28

Browne, Ray B. "Jake Page's Indian Crime Fiction". Journal of American Culture 26, n.º 3 (setembro de 2003): 291–312. http://dx.doi.org/10.1111/1542-734x.00093.

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Chauvier, Éric. "Amy et Jake. Care, réflexivité, négativité". Recherche en soins infirmiers N° 122, n.º 3 (2015): 97. http://dx.doi.org/10.3917/rsi.122.0097.

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Stojanović, Đorđe, e Živojin Đurić. "TEORETSKO ZASNIVANJE KONTINUUMA JAKE-SLABE DRŽAVE". Srpska politička misao 38, n.º 4 (2012): 95–120. http://dx.doi.org/10.22182/spm.3842012.5.

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Gussow, Leon. "The Jake Walk and Limber Trouble". Emergency Medicine News 26, n.º 10 (outubro de 2004): 48. http://dx.doi.org/10.1097/00132981-200410000-00045.

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32

Morrison, Hope. "Jake at Gymnastics by Rachel Isadora". Bulletin of the Center for Children's Books 68, n.º 2 (2014): 110. http://dx.doi.org/10.1353/bcc.2014.0826.

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33

Krygier, John. "Jake Barton’s Performance Maps: An Essay". Cartographic Perspectives, n.º 53 (1 de março de 2006): 41–50. http://dx.doi.org/10.14714/cp53.361.

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Jake Barton, a New York-based designer, creates public maps that generate social interaction, personal expression, and collaborative storytelling. Barton’s work is centered on performance, drawing attention to the performative capacity of maps, a seldom-explored facet of cartographic design and theory. Examples of Barton’s projects, realized and unrealized, are detailed, with a focus on the manner in which maps are designed to evoke performance.

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34

O’Connell, Mark. "Review of A Kid Like Jake". Journal of the American Psychoanalytic Association 62, n.º 2 (abril de 2014): 363–72. http://dx.doi.org/10.1177/0003065114527612.

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35

Shanley, James B., James M. Buttle e Richard P. Hooper. "Preface for Jake Peters' special issue". Hydrological Processes 34, n.º 8 (8 de fevereiro de 2020): 1680–81. http://dx.doi.org/10.1002/hyp.13710.

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36

Lovensheimer, Jim. "Mormons, Musical Theater, and Belonging in America, Jake Johnson (2019) Lying in the Middle: Musical Theater and Belief at the Heart of America, Jake Johnson (2021)". Studies in Musical Theatre 16, n.º 3 (1 de dezembro de 2022): 248–51. http://dx.doi.org/10.1386/smt_00110_5.

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Review of: Mormons, Musical Theater, and Belonging in America, Jake Johnson (2019) Urbana, Chicago and Springfield, IL: University of Illinois Press, 199 pp., ISBN 978-0-25208-433-1, p/bk, $25.00 Lying in the Middle: Musical Theater and Belief at the Heart of America, Jake Johnson (2021) Urbana, Chicago and Springfield, IL: University of Illinois Press, 159 pp., ISBN 978-0-25208-599-4, p/bk, $24.95

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37

Avouac, Jérôme. "Janus Kinase Inhibitor Selectivity in Rheumatoid Arthritis: Where Do We Stand?" Rheumatology 1, n.º 1 (2022): 5. http://dx.doi.org/10.17925/rmd.2022.1.1.5.

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The selectivity of Janus kinase inhibitors (JAKis) is still a matter of debate, as no JAKi is specific for only one Janus kinase (JAK) isoform. Currently approved JAKis in rheumatoid arthritis (RA) all inhibit JAK1, which is an effective therapeutic target in RA. Although selective JAK1 inhibition seems not to decrease drug efficacy, JAKi selectivity may modify the safety profile of this class. Indeed, the balance of benefit and risk of inhibiting JAK2, JAK3 and tyrosine kinase 2 is not certain and should be carefully evaluated in the future.

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Bangerter, Abigail, Nikolay V. Manyakov, David Lewin, Matthew Boice, Andrew Skalkin, Shyla Jagannatha, Meenakshi Chatterjee et al. "Caregiver Daily Reporting of Symptoms in Autism Spectrum Disorder: Observational Study Using Web and Mobile Apps". JMIR Mental Health 6, n.º 3 (26 de março de 2019): e11365. http://dx.doi.org/10.2196/11365.

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Background Currently, no medications are approved to treat core symptoms of autism spectrum disorder (ASD). One barrier to ASD medication development is the lack of validated outcome measures able to detect symptom change. Current ASD interventions are often evaluated using retrospective caregiver reports that describe general clinical presentation but often require recall of specific behaviors weeks after they occur, potentially reducing accuracy of the ratings. My JAKE, a mobile and Web-based mobile health (mHealth) app that is part of the Janssen Autism Knowledge Engine—a dynamically updated clinical research system—was designed to help caregivers of individuals with ASD to continuously log symptoms, record treatments, and track progress, to mitigate difficulties associated with retrospective reporting. Objective My JAKE was deployed in an exploratory, noninterventional clinical trial to evaluate its utility and acceptability to monitor clinical outcomes in ASD. Hypotheses regarding relationships among daily tracking of symptoms, behavior, and retrospective caregiver reports were tested. Methods Caregivers of individuals with ASD aged 6 years to adults (N=144) used the My JAKE app to make daily reports on their child’s sleep quality, affect, and other self-selected specific behaviors across the 8- to 10-week observational study. The results were compared with commonly used paper-and-pencil scales acquired over a concurrent period at regular 4-week intervals. Results Caregiver reporting of behaviors in real time was successfully captured by My JAKE. On average, caregivers made reports 2-3 days per week across the study period. Caregivers were positive about their use of the system, with over 50% indicating that they would like to use My JAKE to track behavior outside of a clinical trial. More positive average daily reporting of overall type of day was correlated with 4 weekly reports of lower caregiver burden made at 4-week intervals (r=–0.27, P=.006, n=88) and with ASD symptoms (r=–0.42, P<.001, n=112). Conclusions My JAKE reporting aligned with retrospective Web-based or paper-and-pencil scales. Use of mHealth apps, such as My JAKE, has the potential to increase the validity and accuracy of caregiver-reported outcomes and could be a useful way of identifying early changes in response to intervention. Such systems may also assist caregivers in tracking symptoms and behavior outside of a clinical trial, help with personalized goal setting, and monitoring of progress, which could collectively improve understanding of and quality of life for individuals with ASD and their families. Trial Registration ClinicalTrials.gov NCT02668991; https://clinicaltrials.gov/ct2/show/NCT02668991

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Palumbo, Matthew D., Francisco J. Vilella, Bronson K. Strickland, Guiming Wang e Dave Godwin. "Brood Surveys and Hunter Observations Used to Predict Gobbling Activity of Wild Turkeys in Mississippi". Journal of Fish and Wildlife Management 5, n.º 1 (1 de janeiro de 2014): 151–56. http://dx.doi.org/10.3996/032013-jfwm-023.

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Abstract The Mississippi Department of Wildlife, Fisheries, and Parks utilize data from turkey hunter observations and brood surveys from across the state to manage wild turkey Meleagris gallopavo populations. Since 1995, hunters have collected gobbling and jake observation data, while the Mississippi Department of Wildlife, Fisheries, and Parks' personnel and cooperating wildlife managers of several natural resource agencies throughout the state have collected brood survey data. Both sources of data serve to forecast poult recruitment and gobbling activity. The objective of this study was to evaluate if these data can serve as a viable predictor of gobbling activity. We used three mixed models to investigate the relationship between the number of jakes observed per hour of hunting 1 y prior and the total number of poults per hens 2 y prior (model 1), number of gobblers heard per hour of hunting and the number of jakes observed per hour of hunting 1 y prior (model 2), the number of gobblers heard per hour of hunting and the total number poults per total hens observed 2 y prior (model 3) using data from 1995 to 2008 among five wild turkey management regions encompassing the state. We incorporated region as a random effect to account for spatial variation. We found the number of jakes observed per hour of hunting 1 y prior correlated with the total number of poults per total hens observed 2 y prior. We also found the number of gobblers heard per hour of hunting correlated with the number of jakes observed per hour of hunting 1 y prior. Additionally, we found that the total poults per total hens observed 2 y prior was correlated to the number of gobblers heard per hour of hunting. Our results show promise for using indices of gobbling activity, jake observations, and brood surveys to estimate gobbling activity.

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Hernandez, Josefino. "Jacob S. Matubis, MD (1950-2022) “Bye, Jake!”". Philippine Journal of Otolaryngology Head and Neck Surgery 37, n.º 1 (5 de junho de 2022): 63. http://dx.doi.org/10.32412/pjohns.v37i1.1943.

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Those words reverberate in our minds as we remember how Dr. Nati Almazan, president of the Philippine Board of Otolaryngology- Head and Neck Surgery, bid Jake goodbye on many occasions, also being a member of the board. Dr. Jacob Sadang Matubis, a colleague, a brother in the Mu Sigma Phi fraternity, and a batchmate during our residency in Otolaryngology-Head and Neck Surgery at the University of the Philippines-Philippine General Hospital from 1981 to 1984, was a friend to many of us. Jake, as we fondly called him, was a member of the UP Medicine Class of 1977, 2 years ahead of my batch, the Class of 1979. During our days at the UP College of Medicine, we joined the UP Medicine football team and competed with the other teams from the different colleges of the University of the Philippines. I played the left-out forward position, now called a striker and Jake was a half-back, now called a midfielder. During our time, we were champions on two occasions, boasting of players who played the game during high school in La Salle Greenhills and Ateneo, as well as having one burly American studying Medicine in UP at that time, playing the defender position. Being champions will always remain happy memories. Jake joined the Mu Sigma Phi fraternity in the summer of 1973. His baritone voice was his ticket to become a member of the Mu Sounds, a singing group of fraternity brothers, together with Dr. Alfee Pontejos, another brother and colleague. They performed in many venues and occasions especially during our fraternity anniversaries and college activities. I would say that Jake was one of the most determined to be an Otorhinolaryngologist-Head and Neck Surgeon, having applied to our department for 3 consecutive years. It didn’t mean that he was not good. It was just unfortunate that when our secretary at that time, Raquel, called their house regarding his application, his mom told her that Jake was going to try to make it in the United States. Upon learning this, Dr. Mariano Caparas, the chair of the department at the time --who was also a pillar of our society and a staunch nationalist— immediately removed Jake from the list of applicants. It took Jake three attempts to convince Dr. Caparas that he was not leaving for the US and that it was his intention to stay in the Philippines and continue to serve the Filipino people--his commitment ever since his UP Diliman days. It was January of 1981 when he started his residency. How Jake ended up as my batchmate during residency was like destiny. Being batchmates, we practically lived together day-in and day-out for 4 years learning surgeries, discussing our patients, spending long days, and sleeping in the call room even during off-duty days, effectively sealing our friendship forever. Back then, we were carefree and we talked a lot about our future. We were fond of playing poker during our downtime. Jake’s favorite game was called “Indian”. Each player would place a card on his forehead without seeing it. You would know the rank of the cards of the other players except yours. You would start giving a bet hoping that the rank of your card is higher compared to the rest. Imagine, if you were betting high while holding in front of your forehead the card 2 of clubs. Everyone would always enjoy laughing at you. You will then realize that you made a wrong bet. We also would always be on guard for Dr. Caparas’ footsteps coming up to our call room. We would immediately hide the cards, clear the table, and scramble to hold a book to make it appear as if we were studying. Dr. Gil Vicente (from one batch after ours), Dr. Jake Matubis, and I were the “barkada” During Residency, Aside from being good friends, we also worked well together. On our senior year in 1984, we won the first and the third prizes for the interesting case contest of the Philippine Society of Otolaryngology-Head and Neck Surgery with papers entitled “Tears from the Parotid” and “Ameloblastoma Arising from a Dentigerous Cyst”. Little did we know that we would also eventually become presidents of the Philippine Society of Otolaryngology-Head and Neck Surgery one after the other from 2008 to 2010. I would say that Jake was a mild-mannered, level-headed, and serious individual, although at times he would start cracking jokes. But the way he attempted to crack these jokes were the real reasons why we would also laugh. He appeared contented with what he had and where he was, especially when he started joining his Christian group. This was the path he took, occasionally addressed by us as “Pastor Jake”, and not hesitating to lead a prayer at the start of our meetings. He joined the Department of Anatomy after finishing residency and eventually became its chair. He became our eternal lecturer for the anatomy of the nose and paranasal sinuses in our yearly post-graduate course in Rhinology since 1992. With him gone, his replacement will have big shoes to fill. Today, people would probably describe Jake as a “chill” guy. He knew his place under the sun. His four children are lucky to have had him as their dad, especially since I have not ever seen him get angry. Thank you, Jake, for the friendship and for touching our lives. Your cool demeanor will always be remembered and emulated. Bye, Jake! See you again my friend, but hopefully not too soon.

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Trihanto, Agung. "An Analysis on Directive Speech Act Found in Jumanji: The Next Level Movie Directed by Jake Kashan". International Journal of English Linguistics, Literature, and Education (IJELLE) 4, n.º 1 (30 de junho de 2022): 13. http://dx.doi.org/10.32585/ijelle.v4i1.2175.

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Directive speech acts are words to order someone so the other people take action according to the request of the speaker both directly and indirectly. This study discusses about An Analysis of Directive Speech Acts Found in Jumanji: The Next Level Movie Directed by Jake Kashan. The purpose of this study is to identify the kinds and the forms of directive speech acts found in Jumanji: The Next Level movie directed by Jake Kashan. This research was conducted using qualitative method. The main instrument of this research is the researcher himself. The researcher as a human instrument used laptop, movie, note book, pen, dictionary as the supporting instrument. The data of this research was collected by documentation and content analysis. The result of the analysis showed 6 types of directive speech acts found in Jumanji: The Next Level Movie Directed by Jake Kashan. They were: 3 data belonging to begging, 49 data belonging to commanding, 6 data belonging to forbidding, 1 data belonging to ordering, 5 data belonging to requesting, 6 data belonging to suggestions. The amount totals of data are 70. The forms of directive speech acts found in The Jumanji: The Next Level Movie Directed by Jake Kashan were declarative, imperative, and interrogative. 11 data belonging to declarative, 54 data belonging to imperative, and 4 data belonging to interrogative.

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Danese, Silvio, Marjorie Argollo, Catherine Le Berre e Laurent Peyrin-Biroulet. "JAK selectivity for inflammatory bowel disease treatment: does it clinically matter?" Gut 68, n.º 10 (21 de junho de 2019): 1893–99. http://dx.doi.org/10.1136/gutjnl-2019-318448.

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The two major forms of inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated conditions characterised by an increased production of pro-inflammatory cytokines that act as critical drivers of intestinal inflammation. Anti-cytokine therapy has been shown to improve clinical outcomes in IBD. Janus kinases (JAKs) are tyrosine kinases that bind different intracellular cytokine receptors, leading to phosphorylation of signal transducer and activation of transcription molecules implicated on targeted gene transcription. Four isoforms of JAKs have been described: JAK1, JAK2, JAK3 and TYK2. Oral JAK inhibitors (JAKi) have been developed as synergic anti-cytokine therapy in IBD, showing different selectivity towards JAK isoforms. Tofacitinib, a pan-JAK inhibitor, has been recently approved for the treatment of moderate-to-severe UC. With the aim of improving the benefit: risk ratio of this drug class, several second-generation subtype-selective JAKi are under development. However, whether selective inhibition of JAK isoforms is associated with an increased clinical efficacy and/or a better safety profile remains debatable. The aim of this review is to critically review the preclinical and clinical data for the differential selectivity of JAK inhibitors and to summarise the potential clinical implications of the selective JAK inhibitors under development for UC and CD.

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Constantinescu, Stefan N., Emilie Leroy, Vitalina Gryshkova, Christian Pecquet e Alexandra Dusa. "Activating Janus kinase pseudokinase domain mutations in myeloproliferative and other blood cancers". Biochemical Society Transactions 41, n.º 4 (18 de julho de 2013): 1048–54. http://dx.doi.org/10.1042/bst20130084.

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The discovery of the highly prevalent activating JAK (Janus kinase) 2 V617F mutation in myeloproliferative neoplasms, and of other pseudokinase domain-activating mutations in JAK2, JAK1 and JAK3 in blood cancers, prompted great interest in understanding how pseudokinase domains regulate kinase domains in JAKs. Recent functional and mutagenesis studies identified residues required for the V617F mutation to induce activation. Several X-ray crystal structures of either kinase or pseudokinase domains including the V617F mutant of JAK2 pseudokinase domains are now available, and a picture has emerged whereby the V617F mutation induces a defined conformational change around helix C of JH (JAK homology) 2. Effects of mutations on JAK2 can be extrapolated to JAK1 and TYK2 (tyrosine kinase 2), whereas JAK3 appears to be different. More structural information of the full-length JAK coupled to cytokine receptors might be required in order to define the structural basis of JH1 activation by JH2 mutants and eventually obtain mutant-specific inhibitors.

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Wang, H. Y., J. Zamorano, J. L. Yoerkie, W. E. Paul e A. D. Keegan. "The IL-4-induced tyrosine phosphorylation of the insulin receptor substrate is dependent on JAK1 expression in human fibrosarcoma cells." Journal of Immunology 158, n.º 3 (1 de fevereiro de 1997): 1037–40. http://dx.doi.org/10.4049/jimmunol.158.3.1037.

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Abstract It has been shown that IL-4 induces the tyrosine phosphorylation of JAK1 and JAK3 in the majority of hemopoietic cell types, and JAK2 and TYK2 in several other types. However, the significance of this tyrosine phosphorylation in regulating IL-4 signaling has not been shown. To determine whether JAKs play a role in activating a signal transduction pathway different from the classical JAK/STAT pathway, we analyzed the ability of huIL-4 to stimulate the tyrosine phosphorylation of one of its major cellular substrates, the insulin receptor substrate (IRS). Using human fibrosarcoma cell lines with mutations in JAK1, JAK2, and TYK2, we found that expression of functional JAK1, but not TYK2 or JAK2, is essential for IL-4-induced tyrosine phosphorylation of IRS. We also provide evidence that the IRS pathway is independent of STAT-6, showing that JAK1 is essential for activating a STAT-independent pathway.

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Evans, Colin. "Jake Thackray, Translator and Interpreter of Brassens". Équivalences 22, n.º 1 (1992): 73–90. http://dx.doi.org/10.3406/equiv.1992.1153.

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Cowell, Eva Lynn. "UNDERSTANDING COMMUNICATION AND AGING By Jake Harwood". Educational Gerontology 34, n.º 11 (22 de outubro de 2008): 1034–35. http://dx.doi.org/10.1080/03601270802432332.

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Ramsey, Sarah Schwartzman. "Yekl to Jake: Reading Cahan with Arendt". Studies in American Jewish Literature (1981-) 42, n.º 2 (1 de setembro de 2023): 141–57. http://dx.doi.org/10.5325/studamerijewilite.42.2.0141.

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Abstract In Abraham Cahan’s 1896 novella, Yekl: A Tale of the New York Ghetto, Yekl/Jake is a Russian Jewish immigrant who repeats loud and self-aggrandizing accounts of himself as a proudly assimilated American. This article uses Hannah Arendt’s writing on cliché and her 1943 essay “We Refugees” to argue that Cahan’s depiction of Jake exemplifies a type of performance, one that Arendt witnessed among Jewish refugees during her own experiences of displacement: a pattern of narrative erasure and fabrication, alienation from community, and “insane optimism which is next door to despair” (Arendt [1943] 2007, 268). While recent scholarship has deftly explored performances of American identity related to gender and language in the novella, less attention has been paid to identifiable patterns of self-narrative: in particular, the pressure to give an account of oneself as already having been a compatriot, and the inevitable fissures that undermine such hopeful but fabricated stories.

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Zhong, Haizhen A., e Suliman Almahmoud. "Docking and Selectivity Studies of Covalently Bound Janus Kinase 3 Inhibitors". International Journal of Molecular Sciences 24, n.º 7 (23 de março de 2023): 6023. http://dx.doi.org/10.3390/ijms24076023.

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The Janus kinases (JAKs) are a family of non-receptor cytosolic protein kinases critical for immune signaling. Many covalently bound ligands of JAK3 inhibitors have been reported. To help design selective JAK inhibitors, in this paper, we used five model proteins to study the subtype selectivity of and the mutational effects on inhibitor binding. We also compared the Covalent Dock programs from the Schrodinger software suite and the MOE software suite to determine which method to use for the drug design of covalent inhibitors. Our results showed that the docking affinity from 4Z16 (JAK3 wild-type model), 4E4N (JAK1), 4D1S (JAK2), and 7UYT (TYK2) from the Schrödinger software suite agreed well with the experimentally derived binding free energies with small predicted mean errors. However, the data from the mutant 5TTV model using the Schrödinger software suite yielded relatively large mean errors, whereas the MOE Covalent Dock program gave small mean errors in both the wild-type and mutant models for our model proteins. The docking data revealed that Leu905 of JAK3 and the hydrophobic residue at the same position in different subtypes (Leu959 of JAK1, Leu932 of JAK2, and Val981 of TYK2) is important for ligand binding to the JAK proteins. Arg911 and Asp912 of JAK3, Asp939 of JAK2, and Asp988 of TYK2 can be used for selective binding over JAK1, which contains Lys965 and Glu966 at the respective positions. Asp1021, Asp1039, and Asp1042 can be utilized for JAK1-selective ligand design, whereas Arg901 and Val981 may help guide TYK2-selective molecule design.

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Liu, X., F. Tan e C. Liang. "THU0080 PRECLINICAL CHARACTERIZATION OF TLL018, A NOVEL, HIGHLY POTENT AND SELECTIVE JAK1/TYK2 INHIBITOR FOR TREATING AUTOIMMUNE DISEASES". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 252.1–252. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1547.

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Background:Janus kinases (JAKs) are important regulators of intracellular responses triggered by many key proinflammatory cytokines and are clinically validated therapeutic targets for treating various autoimmune diseases. However, current approved JAK inhibitors failed to achieve maximal clinical benefit in part due to their unfavorable selectivity for individual JAKs such as JAK2 and/or JAK3, leading to dose-limiting toxicities or severe toxicities (e.g., thrombosis, anemia, immune suppression). Selective inhibition of JAK1 and/or TYK2 may minimize or avoid some of the toxicities and potentially offer a better therapeutic window for treating autoimmune diseases. No highly selective JAK1/TYK2 inhibitor has been reported to date.Objectives:Discovery of a highly selective JAK1/TYK2 inhibitor that maximally avoids JAK2 and JAK3 inhibition. We described preclinical characterization of a novel, highly potent and selective JAK1/TYK2 inhibitor TLL018 and its potential utility in treating autoimmune diseases such as rheumatoid arthritis (RA).Methods:Using predicting SAR, TLL018 was designed to achieve exquisite selectivity for both JAK1 and TYK2 while sparing JAK2, JAK3 and other human kinases. Its enzyme and cell activities, kinase selectivity, andin vivoefficacy were assessed in a battery of relevant enzyme, cell and whole blood assays, andin vivoarthritis animal models. Additional preclinical DMPK and toxicology studies were conducted to support its clinical development.Results:TLL018 is a highly potent and selective, orally bioavailable JAK1/TYK2 inhibitor against JAK1 (IC50= 4 nM) and TYK2 (IC50= 5 nM) as measured inin vitrokinase assays with ATP concentrations at individual Km. Its potency against JAK2 or JAK3 is greater than 1 µM. Profiling against a panel of over 350 human kinase showed that TLL018 is exclusively selective for JAK1 and TYK2, with ≥ 90-fold selectivity against all other kinases tested. TLL018 exhibited potent cellular activity for JAK1-mediated IL-6 signaling (IC50= 0.6 µM) with greater than 100-fold selectivity against JAK2-mediated cytokine (e.g., TPO) signaling in human whole blood-based assays.Oral administration of TLL018 demonstrated dose-dependent efficacy in commonly studied rat adjuvant-induced arthritis (rAIA) model and mouse collagen-induced arthritis (mCIA) model. Significant inhibition of inflammation, bone resorption, splenomegaly and body weight change was observed in adjuvant-induced disease in rats. In addition, significant inhibition of inflammation, cartilage destruction, bone resorption and histological signs was demonstrated in collagen-induced arthritis in mice. Noticeably, TLL018 exhibited significant anti-inflammation activity at doses that only blocked JAK1 and TYK2 and exerted little inhibition of JAK2 and JAK3.In support of clinical development of TLL018, preclinical ADME and PK studies and IND-enabling toxicology and safety pharmacology studies were completed, confirming that TLL018 possesses excellent ADME and PK properties, and exhibits a clean on-target safety profile.Conclusion:TLL018 is a highly potent and selective JAK1/TYK2 inhibitor that demonstrated excellent efficacy and tolerability in relevant mouse and rat arthritis models. The collective data of its preclinical pharmacology, PK and toxicology showed a favorable pharmaceutical profile, further supporting its development for treating autoimmune diseases including RA. Clinical evaluation of TLL018 is ongoing.Disclosure of Interests:Xiangdong Liu Shareholder of: I own shares of TLL Pharmaceutical LLC, Employee of: I am employed by TLL Pharmaceutical LLC, Fenlai Tan Shareholder of: I own shares of TLL Pharmaceutical LLC, Employee of: I am employed by TLL Pharmaceutical LLC, Chris Liang Shareholder of: I own shares of TLL Pharmaceutical LLC, Employee of: I am employed by TLL Pharmaceutical LLC

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Widayanto, Mutinda Teguh. "Sosialisasi Pembuatan Pokak Jahe Untuk Meningkatkan Imunitas Dimasa Pandemi Covid-19 di Sumberkedawung Leces Probolinggo". Dharma: Jurnal Pengabdian Masyarakat 1, n.º 2 (10 de junho de 2021): 93–110. http://dx.doi.org/10.35309/dharma.v1i2.4531.

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Pandemi Covid-19 yang melanda hampir seluruh wilayah di dunia telah mempengaruhi berbagai sektor kehidupan masyarakat. Pembatasan kegiatan masyarakat karena menghindari penyebaran virus menyebabkan aqktivitas tidak bisa dilaksanakan sebagaimana mestinya. Bidang pendidikan, sosial dan ekonomi tak luput dari pengaruh tersebut. Upaya untuk mengatasi penularan virus juga dilakukan. Berbagai penelitian dilakukan untuk mengatasi permasalahan tersebut. Salah satu faktor yang dapat mengatasi dampak dari serangan virus adalah adanya imunitas tubuh yang baik. Minuman tradisional Pokak Jahe diketahui mengandung bahan herbal yang mempunyai khasiat dapat meningkatkan imunitas tubuh dari serangan virus. Kegiatan pengabdian masyarakat berupa sosialisasi pembuatan Pokak Jahe ini bertujuan untuk memberi pemahaman manfaat dan mensosialisasican cara pembuatan minuman Pokak Jahe sebagai minuman tradisional yang bermanfaat untuk meningkatkan imunitas tubuh di masa pandemi Covid-19 ini. Diharapkan masyarakan memahami manfaat tersebut dan mampu membuat minuman Pokak Jake untuk dikonsumsi dan untuk dikomersiilkan sehingga dapat meningkatkan imunitas mereka.

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