Artykuły w czasopismach: „Jake”

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

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Chudnov, Daniel, Cynthia Crooker i Kimberly Parker. "jake". Serials Review 26, nr 4 (grudzień 2000): 12–17. http://dx.doi.org/10.1080/00987913.2000.10764619.

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Gonzalez-Traves, P., B. Murray, F. Campigotto, A. Meng i 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 (czerwiec 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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Lees, J. A., P. R. Bown i J. R. Young. "Jake Hancock: reminiscences". Proceedings of the Geologists' Association 117, nr 2 (styczeń 2006): 125–27. http://dx.doi.org/10.1016/s0016-7878(06)80004-0.

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

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Deverell, William, i Tom Sitton. "Forget it, Jake". Boom 3, nr 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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Scaife, B. "John ("Jake") Stohlner". BMJ 324, nr 7352 (22.06.2002): 1527e—1527. http://dx.doi.org/10.1136/bmj.324.7352.1527/e.

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

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

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Spaner, D., M. Iqbal, A. Navabi, K. Strenzke i B. Beres. "Jake hard red spring wheat". Canadian Journal of Plant Science 100, nr 1 (1.02.2020): 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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Silver, Joel. "EXIT INTERVIEW: JAKE CHERNOFSKY". RBM: A Journal of Rare Books, Manuscripts, and Cultural Heritage 1, nr 1 (1.03.2000): 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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Shannon, J. G., J. A. Wrather, D. A. Sleper, R. T. Robbins, H. T. Nguyen i S. C. Anand. "Registration of ‘Jake’ Soybean". Journal of Plant Registrations 1, nr 1 (maj 2007): 29–30. http://dx.doi.org/10.3198/jpr2006.05.0347crc.

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

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Tacchi, Derek. "James (“Jake”) Knox Russell". BMJ 334, nr 7594 (22.03.2007): 643.5–643. http://dx.doi.org/10.1136/bmj.39155.563796.be.

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

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

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

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

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Shankar, Guha. "Discovering Rastafari! by Jake Homiak". American Anthropologist 113, nr 3 (24.08.2011): 508–9. http://dx.doi.org/10.1111/j.1548-1433.2011.01363.x.

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

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Silverstone, Daniel, i Joe Whittle. "‘Forget it, Jake. It’s Chinatown’". Police Journal: Theory, Practice and Principles 89, nr 1 (26.02.2016): 70–84. http://dx.doi.org/10.1177/0032258x16631566.

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

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Browne, Ray B. "Jake Page's Indian Crime Fiction". Journal of American Culture 26, nr 3 (wrzesień 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, nr 3 (2015): 97. http://dx.doi.org/10.3917/rsi.122.0097.

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Stojanović, Đorđe, i Živojin Đurić. "TEORETSKO ZASNIVANJE KONTINUUMA JAKE-SLABE DRŽAVE". Srpska politička misao 38, nr 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, nr 10 (październik 2004): 48. http://dx.doi.org/10.1097/00132981-200410000-00045.

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

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

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Krygier, John. "Jake Barton’s Performance Maps: An Essay". Cartographic Perspectives, nr 53 (1.03.2006): 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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Shanley, James B., James M. Buttle i Richard P. Hooper. "Preface for Jake Peters' special issue". Hydrological Processes 34, nr 8 (8.02.2020): 1680–81. http://dx.doi.org/10.1002/hyp.13710.

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Constantinescu, Stefan N., Emilie Leroy, Vitalina Gryshkova, Christian Pecquet i Alexandra Dusa. "Activating Janus kinase pseudokinase domain mutations in myeloproliferative and other blood cancers". Biochemical Society Transactions 41, nr 4 (18.07.2013): 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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Palumbo, Matthew D., Francisco J. Vilella, Bronson K. Strickland, Guiming Wang i Dave Godwin. "Brood Surveys and Hunter Observations Used to Predict Gobbling Activity of Wild Turkeys in Mississippi". Journal of Fish and Wildlife Management 5, nr 1 (1.01.2014): 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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Bangerter, Abigail, Nikolay V. Manyakov, David Lewin, Matthew Boice, Andrew Skalkin, Shyla Jagannatha, Meenakshi Chatterjee i in. "Caregiver Daily Reporting of Symptoms in Autism Spectrum Disorder: Observational Study Using Web and Mobile Apps". JMIR Mental Health 6, nr 3 (26.03.2019): 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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Danese, Silvio, Marjorie Argollo, Catherine Le Berre i Laurent Peyrin-Biroulet. "JAK selectivity for inflammatory bowel disease treatment: does it clinically matter?" Gut 68, nr 10 (21.06.2019): 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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Evans, Colin. "Jake Thackray, Translator and Interpreter of Brassens". Équivalences 22, nr 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, nr 11 (22.10.2008): 1034–35. http://dx.doi.org/10.1080/03601270802432332.

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Liu, X., F. Tan i 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 (czerwiec 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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Spinelli, Francesca Romana, Robert A. Colbert i Massimo Gadina. "JAK1: Number one in the family; number one in inflammation?" Rheumatology 60, Supplement_2 (1.05.2021): ii3—ii10. http://dx.doi.org/10.1093/rheumatology/keab024.

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Abstract Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine. JAK1 is involved in the signalling of ‘γc’ receptor cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), pro-inflammatory cytokines including IL-6, as well as IFN. The critical position of JAK1 downstream of these cytokines suggests that JAK1-selective inhibitors are comparable to non-selective ones, without the unwanted consequences of JAK2- or JAK3-blockade. JAK inhibition has led to a better understanding of the biology of synovial inflammation and bone homeostasis. Moreover, the efficacy of non-selective JAK inhibitors and novel JAK1-selective drugs in RA supports a role for JAK1 in its pathogenesis. JAK1-selective drugs are also showing promise in axial spondyloarthritis, suggesting that they may target additional regulatory pathways that impact cytokines such as TNF and IL-17A, which do not use JAKs. Additionally, evidence now supports a JAK1 predominance in the signalling of IL-6 and oncostatin M, and indirectly, of TNF in synovial fibroblasts, macrophages and endothelial cells. Notably, bone homeostasis is also dependent on cytokines relying on JAK1 signalling to promote receptor activator of NF-κB ligand expression in osteoblasts and T cells, contributing to osteoclastogenesis. Here, the contribution of JAK1 over other kinases is unclear. While beneficial effects of JAK inhibitors on bone erosion are supported by preclinical and clinical data, effects on new bone formation in axial spondyloarthritis requires additional study. CME: This supplement is CME Accredited. To receive a CME certificate of participation, you should: Read all the papers in the supplement Register or log in at www.paradigmmc.com/962 to complete and submit the post activity assessment. You must answer 70% of the questions correctly to earn credit. You will have unlimited opportunities to successfully complete the assessment. You will receive a maximum of 7.0 AMA PRA Category 1 CreditsTM upon successful completion of the assessment.

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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, nr 2 (10.06.2021): 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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Deutsche, Rosalyn. ""Chinatown," Part Four? What Jake Forgets about Downtown". Assemblage, nr 20 (kwiecień 1993): 32. http://dx.doi.org/10.2307/3181686.

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Selley, R. C. "Jake Hancock at Imperial College, London (1986–1993)". Proceedings of the Geologists' Association 117, nr 2 (styczeń 2006): 123–24. http://dx.doi.org/10.1016/s0016-7878(06)80003-9.

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Beaudet, Bob, John Acquaviva i Dan Grube. "Jake Sport Education a Step further: Add fitness". Journal of Physical Education, Recreation & Dance 75, nr 9 (listopad 2004): 39–43. http://dx.doi.org/10.1080/07303084.2004.10607299.

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Neubert, Michael, i Michael Brewer. "Using JAKE: A Guide for the Slavic Specialist". Slavic & East European Information Resources 3, nr 4 (wrzesień 2002): 79–84. http://dx.doi.org/10.1300/j167v03n04_08.

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Liović, Marica. "Jake žene Kozarčeve: o Kati, Teni, Miri, Jeleni". Posebna izdanja / Hrvatska akademija znanosti i umjetnosti, Centar za znanstveni rad u Vinkovcima 28 (2017): 175–216. http://dx.doi.org/10.21857/y7v64t5xpy.

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Hedden, P., i M. H. Beale. "Jake MacMillan: A pioneering chemist in plant biology". Proceedings of the National Academy of Sciences 111, nr 41 (3.10.2014): 14641–42. http://dx.doi.org/10.1073/pnas.1414365111.

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Balderson, Quinita. "The Taking of Jake Livingston by Ryan Douglass". Bulletin of the Center for Children's Books 74, nr 11 (2021): 463. http://dx.doi.org/10.1353/bcc.2021.0364.

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Karkowska, Magda. "Narracyjne strategie tworzenia tożsamości – wokół biograficznych opowieści". Biografistyka Pedagogiczna 5, nr 1 (8.09.2020): 241–62. http://dx.doi.org/10.36578/bp.2020.05.16.

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Celem, jaki postawiła przed sobą autorka artykułu, jest przeanalizowanie procesu konstruowania tożsamości i pewnych jej strategii na szerszym tle, jakie tworzą rozważania o wybranych typach narracji i ich związkach z jaźnią jednostki. Istotnym punktem analizy jest poszukiwanie odpowiedzi na pytanie jaką rolę w procesie konstruowania tożsamości pełnią schematy i wzorce narracyjne obecne w kulturze i jakie czynniki mogą definiować ów wpływ?Równie ważną kwestią wydają się być uwarunkowania tworzenia przez ludzi tzw. autonarracji proaktywnych i defensywnych, będących podstawą do rozwijania określonych strategii tożsamości jako pochodnej związków między jednostką, jej wyobrażeniami o własnym działaniu i jego motywach a otoczeniem.

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Montresor, Alessio, Matteo Bolomini-Vittori, Lara Toffali, Barbara Rossi, Gabriela Constantin i Carlo Laudanna. "JAK tyrosine kinases promote hierarchical activation of Rho and Rap modules of integrin activation". Journal of Cell Biology 203, nr 6 (23.12.2013): 1003–19. http://dx.doi.org/10.1083/jcb.201303067.

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Lymphocyte recruitment is regulated by signaling modules based on the activity of Rho and Rap small guanosine triphosphatases that control integrin activation by chemokines. We show that Janus kinase (JAK) protein tyrosine kinases control chemokine-induced LFA-1– and VLA-4–mediated adhesion as well as human T lymphocyte homing to secondary lymphoid organs. JAK2 and JAK3 isoforms, but not JAK1, mediate CXCL12-induced LFA-1 triggering to a high affinity state. Signal transduction analysis showed that chemokine-induced activation of the Rho module of LFA-1 affinity triggering is dependent on JAK activity, with VAV1 mediating Rho activation by JAKs in a Gαi-independent manner. Furthermore, activation of Rap1A by chemokines is also dependent on JAK2 and JAK3 activity. Importantly, activation of Rap1A by JAKs is mediated by RhoA and PLD1, thus establishing Rap1A as a downstream effector of the Rho module. Thus, JAK tyrosine kinases control integrin activation and dependent lymphocyte trafficking by bridging chemokine receptors to the concurrent and hierarchical activation of the Rho and Rap modules of integrin activation.

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Hughes, Rachel. "Race, Colonialism and Vegetative Life". Cultural Studies Review 10, nr 2 (30.08.2013): 200–204. http://dx.doi.org/10.5130/csr.v10i2.3508.

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