Journal articles: 'PRO Cook' – Grafiati (2024)

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The Cook Strait in New Zealand is an ideal location for wind and tidal renewable sources of energy due to its strong winds and tidal currents. The integration of both technologies can help to avoid the detrimental effects of fossil fuels and to reduce the cost of electricity. Although tidal renewable sources have not been used for electricity generation in New Zealand, a recent investigation, using the MetOcean model, has identified Terawhiti in Cook Strait as a superior location for generating tidal power. This paper investigates three different configurations of wind, tidal, and wind plus tidal sources to evaluate tidal potential. Several simulations have been conducted to design a DC-linked microgrid for electricity generation in Cook Strait using HOMER Pro, RETScreen, and WRPLOT software. The results show that Terawhiti, in Cook Strait, is suitable for an offshore wind farm to supply electricity to the grid, considering the higher renewable fraction and the lower net present cost in comparison with those using only tidal turbines or using both wind and tidal turbines.

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Poor eating habits are increasing the prevalence of weight-related issues, such as diabetes and cardiovascular diseases. Given the demand to improve individuals’ food knowledge and competencies aiming at healthier behaviours, the current investigation explores the concept of food literacy. Considering the lack of a shared understanding of food literacy, this study aims to explore food literacy’s domains, influential factors and determinants. Using a qualitative deductive-dominant content analysis, 30 experts from food-related fields were interviewed. The obtained outcomes were compared to available food literacy frameworks. Agreement among inter-raters was nearly perfect (k = 0.82). Yielding a total of 184 codes nested within 19 categories, identified domains were Origin, Safety, Choice and Decision, Select and Acquire, Plan, Preserve, Prepare, Cook, and Knowledge; influential factors included Nutrition, Psychological, Health, Learning Contexts, Policy, Industry, Sustainability, and Social and Cultural; External determinants were “Access to Food-Related Information”, “Perishable and/or Unreliable Food-Related Information”, “Family Dynamic and/or Identity”, and “Professionals’ Unpreparedness on Food-Related Expertise”, and Internal determinants included “Prioritise Food”, “Convenience and Practicality”, “Time and Financial Management”, “Previous Food-Related Habits”, and “Innate and Learned Flavour Preferences”. In conclusion, more than half of the identified attributes (62.5%) are corroborated by the current literature. However, the manifested content unmatched with the current frameworks of food literacy literature express food-literacy-related fields of action, knowledge, competencies, and determinants that have not yet been explored. As such, this study provides new and useful information concerning food literacy definition and development, by identifying its domains, factors of influence, and potential determinants. Moreover, this work paves the way for new measurements and interventions within this field.

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Purpose The purpose of this paper is to demonstrate the benefits of cooking one-to-one, alongside commensality (eating together) for improving offenders’/ex-offenders’ health and well-being, measured in terms of improved social skills, cultural competencies and successful resettlement. Design/methodology/approach Fieldwork conducted over nine months included; participant observation of lunch times (n=56) and cooking one-to-one with trainees (n=27), semi-structured interviews (n=23) and a “photo-dialogue” focus group with trainees (n=5) and staff (n=2). Findings Commensality is beneficial for offenders’ health and well-being. Further, preparing, cooking, serving and sharing food is a powerful means of improving self-esteem and developing a pro-social identity. Research limitations/implications The original focus of the research was commensality; it was during the study that the potential for cooking as an additional tool for health and well-being emerged. A future longitudinal intervention would be beneficial to examine whether the men continued to cook for others once released from prison and/or finished at the resettlement scheme. Practical implications Everyday cooking to share with others is an invaluable tool for improving self-worth. It has the potential to build pro-social self-concepts and improve human, social and cultural capital. Social implications Cooking lunch for others is a part of strengths-based approach to resettlement that values community involvement. Originality/value Cooking and eating with offenders/ex-offenders is highly unusual. Further hands-on cooking/eating activities are beneficial in terms of aiding self-confidence and self-respect, which are vital for improving offenders’/ex-offenders’ health and well-being.

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In this study, physical (cooking time, water ab-sorption, cooking loss and color), chemical (proximate composition, pH, total phe-nolic content, mineral mat-ter (Ca, K, Fe, Mg and Zn)), textural (hardness and adhe-siveness) and sensory (col-or, taste, flavor, appearance, hardness, adhesiveness and overall acceptability) attrib-utes were determined in dif-ferent types of noodles pro-duced from siyez wheat flour, kale powder and chia seed mucilage. Results were statistically evaluated using SAS software. The optimal cooking time for the noo-dles were 20 min and cook-ing loss varied between 8.36-12.22%. Kale powder and chia mucilage addition decreased L* and a* values of the noodles. Ash, crude fiber, mineral matter and total phenolic contents of the noodles were higher and fat contents of the noodles were lower than the control sample. Hardness and adhe-siveness of the noodles were decreased by addition of the kale powder at 10%. The noodles with higher hard-ness and lower adhesiveness were preferred by the panel-ists in sensory evaluation. Increasing the kale powder level in the noodle formula-tion from 5% to 10% result-ed in higher color scores. However, the control sam-ple was the most preferred sample in terms of taste.

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Apples ( Malus pumila ) such as Anna and Dorsett Golden are varieties with limited fresh commercial usage due to their small size, high acidity and scarce red pigmentation. However, they can be pro cessed to make applesauce that can be used as an ingredient in the elaboration of meat products. A bologna-type product was produced replacing fat with 15% applesauce ( Anna, Dorsett Golden and Golden Delicious varieties) to evaluate chemical, physical and sensory properties. Mechanically deboned turkey meat and pork shoulder was used. Ten and twenty percent of backfat and regular fat were added to products with applesauce and the control sample, respectively. Addition of applesauce to the formulation had no effect on cook yield after thermal processing, which was 96%. A 25% fat reduction was accomplished in the finished product with respect to the control. Moisture increased from 56% in the control to 63% in bologna sausage with applesauce. There were no effects on texture parameters and there was a lowering effect ( p < 0.05) in L value for lightness by applesauce addition. Bologna sausage with Golden Delicious apple sauce was the sweetest as evaluated by panelists. In overall acceptability for all bologna sausages, scores ranged between acceptable and good. It is advis able to use applesauce as an ingredient in emulsion-type products like bologna sausages to replace fat and still produce an acceptable product.

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Abstract Porcine small intestinal submucosa (SIS) of Cook Biotech is widely used in tissue remodeling. It also proved safe and effective in enhancing efficacy of a prostate cancer vaccine. In this study, we compared SIS-adjuvanticity with alum’s in mobilizing innate immunity via inflammasomes, and in boosting antibody response to soluble proteins, ovalbumin, and a hapten-protein conjugate, phthalate-KLH. This evaluation carried out in BALB/c, C57Bl/6 and lupus-prone NZB/WF1 mice was done by both Intraperitoneal and subcutaneous routes of immunization. Methods involved determination of antibody titer, isotyping, microarray profiling of cytokines and chemokines and qPCR of inflammasomes-related genes. Results clearly highlighted the difference between SIS and alum. SIS provoked neither pro-inflammatory cytokines (IL-6, IL-1β, and TNFα) nor NLRP3 inflammasomes as alum did, but it did up-regulate IL4 and CD30-ligand. SIS also activated chemotactic factors LIX and KC (neutrophil chemotactic factors), MCP 1 (monocyte chemotactic factors), MCSF and MIP 1-α (macrophage chemotactic factor) and Lympotactin, albeit a little less than Alum. SIS, however, was as effective as alum in engendering lasting and specific antibody responses, primarily of IgG1 type, but proved inconsequential in induction of anti-DNA response or renal pathology. In conclusion, although both alum and SIS induced Th2 type immune response, SIS was much less inflammatory than alum.

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Abstract Introduction: Advances in technology and internet capability have provided an opportunity for efficient collection of Patient Reported Outcomes (PRO) during medical treatment. Here we describe the development and implementation of a system for monitoring patient reported adverse events (AEs) and quality of life (QoL) using electronic PRO (ePRO) instruments for patients enrolled on the Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis (I-SPY 2 TRIAL), a phase II adaptive platform clinical trial for locally advanced breast cancer. Methods: We designed an ePRO system to increase the accuracy of patient-reported QoL and AE data collection with the intent to act on symptoms in real time. Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY 2 treatment schedule. Weekly surveys contained a maximum of 126 validated, branching logic questions from the Patient Reported Outcomes Measurement Information System (PROMIS®) Health Measures and the National Cancer Institute’s Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE™) instruments. We piloted ePROs at the University of California, San Francisco (UCSF) to evaluate compatibility with a variety of I-SPY 2 patient scenarios (e.g., dose delays). We then staggered rollout of the ePRO system to 22 I-SPY 2 sites to ensure technological feasibility. In order to improve accuracy of data collection, we utilized real-time tracking and developed a Clinical Research Coordinator (CRC) training manual, which integrated workflow diagrams with technical solutions. CRCs were trained using remote video sessions. Results: The UCSF ePRO pilot began in September of 2020. Over 9-months, we accrued 43 I-SPY 2 patients (average age of 43.8 years), whose interactions with the ePRO system informed design improvements. Of the patients who received a baseline ePRO survey, the completion rate was 75.9% (average age of 44.2 years). This represents an increase from the 15-20% baseline completion rate for the 360 UCSF I-SPY 2 patients who received paper-based PRO surveys between May 2012 - January 2019. As of June 2021, the ePRO system was operational at all 22 I-SPY 2 sites. The UCSF pilot revealed that engagement with patients at critical timepoints improved survey completion. CRCs facilitated patient participation by sending instructional emails and communicating with patients weekly. We tracked data completeness using a Patient Tracking report, which displayed each patient’s survey completion history. This real-time tool enabled CRCs to identify patients who had not completed ePRO surveys prior to their visit, so they could be provided a tablet computer to complete the survey in the clinic. After introducing tablets into the workflow at UCSF, patient completion of the baseline survey increased from 75.9% to 80%. Conclusion: The transition from paper to electronic QOL and AE data collection improves the ability of patients to complete PRO surveys, but the process must also be optimized and integrated into clinical workflow and trial conduct. In the future, we will present additional results highlighting the feasibility of multilingual ePRO integration into I-SPY 2. ePRO also provides a new opportunity for data analysis, as well as the potential to reduce high grade toxicity through early intervention. It will allow us to assess QoL and AE data by drug regimen, site, provider, and study treatment. The creation of clinician-facing reports also enables access to patient responses in real-time. By implementing ePRO within I-SPY 2, we not only increase efficiency and accuracy of patient-reported data collection, but also improve quality of care and patient safety. Citation Format: Anna Northrop, Anika Christofferson, Michelle Melisko, Laura Sit, Ebunoluwa Olunuga, Ananya Mittal, Adi Goldman, Thelma Brown, Diane Heditsian, Bev Parker, Susie Brain, Carol Simmons, Alessandra Taboada, Kathryn J Ruddy, Tina Hieken, Mara Piltin, Kiri Cook, Carolina Salvador, Candace Mainor, Anosheh Afghahi, Sarah Tevis, Anne Blaes, Irene Kang, Susan Melin, Laura Esserman, Adam Asare, Dawn L Hershman, Amrita Basu. Improving patient-reported outcome data capture for clinical research: ePRO in ISPY 2, a phase 2 breast cancer study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-02.

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DAWN: A Proton's Tale of All That Came to Be by Cees Dekker, Corien Oranje, and Gijsbert van den Brink. Translated by Harry Cook. Downers Grove, IL: InterVarsity Press, 2022. 166 pages, discussion questions. Paperback; $22.00. ISBN: 9781514005668. *Imagine that you could witness the entire history of the universe first-hand, from the big bang to the end of time. Perhaps, if you were a sentient yet patient proton, you would have the necessary longevity and attention span, and this idea could become your reality. Such is the premise of Dawn: A Proton's Tale of All That Came to Be. "Pro," as the proton protagonist is known to his chatty neighboring subatomic particles, is born from quarks in the first second after the big bang, blind and knowing nothing, but with an insatiable curiosity about what is happening, and why. Conversations with other particles born a split-second earlier soon produce in Proton a deep admiration for a skilled Creator, and a sense of wonder and anticipation about what they have seen and what will happen next. *Throughout several chapters, Pro confusedly and vividly experiences the onset of light, nuclear fusion, a supernova, and incorporation into a molecule as part of a carbon nucleus. Pro ends up in the dust cloud that forms Earth, eventually witnessing the origin of terrestrial life as part of an RNA molecule. A rumor among the subatomic particles that the Creator wants to make personal contact with one of the creatures generates a guessing game as they witness the progress of evolution. Which lifeform will it be? *When hom*o sapiens arrive on the scene, the story shifts to tracking biblical narratives, and the subatomic particles begin asking each other more theological questions. The Creator makes contact with two humans, a chieftain couple in Africa. The Fall ensues when the couple and their tribe reject the Creator's instructions, much to the subatomic particles' surprise and horror. Pro and his neighbors are then able to witness key moments in the progress of redemption, becoming fly-on-the-wall observers to events in the lives of several important biblical characters. "How is the Creator going to fix things?" the particles ask each other. *At this point it becomes apparent what a colossal challenge the three authors (a nano scientist, a novelist, and a theologian)1 have taken upon themselves. They have tried to produce a gripping narrative in which the protagonist does not know the outcome, but Christian readers will. They have set out to tell an entertaining story of the history of the universe from a Christ-centered perspective, filled with imaginative details that are consistent with modern science but also with the biblical witness. They have charged into a literary no man's land between fiction and nonfiction. *Do they succeed? In many ways, admirably so. The merging of science and biblical witness is skillfully accomplished, respecting the integrity of each source of knowledge. To readers of this journal, the idea of a Creator patiently guiding the evolution of the universe and of life over billions of years in order to generate Earth and its humanity, followed by the increasingly intimate involvement of that Creator in redeeming humanity, is familiar. To many others, this idea will be revelatory. *If evaluated as a work of fiction, it would be safe to say that Dawn is wildly imaginative, yet it is also strangely hindered by the passivity of the narrating subatomic particles. "Imagine that you yourself could determine where you would like to go" (p. 28), they muse just before the first protocell develops. Pro witnesses and experiences history but cannot intervene. The subatomic particles can react, but they have no agency in the macroscopic world. They do not embark on a quest or a voyage of self-discovery. "Just go with the flow" (p. 29), one advises. The tropes of fiction, however, are probably the wrong standards for evaluating this book. *Dawn succeeds, in the end, as creative nonfiction--the memoir of a proton. Along the way, it retells the old, old story in an imaginative way. The authors have created one of the most accessible books on science and Christianity to come out in recent years. Even young adults will be able to enjoy it. *Note *1Cees Dekker, distinguished nano-scientist at Delft University of Technology; Corien Oranje, novelist/theologian and author of Christian children's literature; and Gijsbert van den Brink, theologian and holder of the Chair of Theology and Science, Vrije Universiteit Amsterdam. *Reviewed by David O. De Haan, Professor of Chemistry, University of San Diego, San Diego, CA 92110.

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Abstract Introduction. The impact of therapy in the management of disease relapse in patients with myeloma (MM) needs to be balanced with the impact on quality of life (QoL). The benefit of a salvage autologous stem cell transplant (ASCT2) has been demonstrated in terms of durability of response over non-transplant consolidation (NTC) (G Cook, et al., Lancet Oncology, 2013 Vol. 15, No. 8, p874-885). However, the impact of ASCT2 on patient reported outcomes (PRO) has not been reported to date. Therefore, patients' experience of pain and global measures of QoL, as part of a systematic assessment of PRO were measured at key points before, during and after randomisation in this multi-centre national phase III trial. Methods. 174 patients were randomised and data are presented on 171 who completed self-rated QoL assessments using EORTC QLQ-C30 and the EORTC myeloma module (MY-20). Pain assessments using BPI-SF were also incorporated. Genomic DNA was prepared from PBMNC using standardised GLP methods. Results. Completion rates for EORTC QoL and BPI-SF assessments were 83.3% and 77.1% at registration, and 59.6% and 53.8% at randomisation, respectively. Over half of patients reaching 1 year post-randomisation completed both assessments. EORTC QoL and BPI-SF forms had average 6% and 10% missing data, respectively. These completion rates are commensurate with previous longitudinal studies. EORTC QLQ-C30 Global health status/QoL subscale scores were significantly higher (better) in the NTC arm at 100 days and 6 month post-randomisation (P=0.0496), but not at later time points. BPI-SF pain scores showed significantly higher pain severity in the NTC (4.3/10) than the ASCT2 (2.9/10) patients only at 2 years post-randomisation. However, for pain interference with aspects of daily living, NTC patients reported significantly lower scores at 6 months (P=0.0155), 1 year post-randomisation (P=0.0466) and 2 years post-randomisation (P=0.0348). The MY-20 assessment showed that at 100 days and 6 months post-randomisation, the subscale scores for Side-effects of treatment were significantly higher in the ASCT2 arm than in the NTC arm, but not at later time points up to 2 years. Kaplan-Meier estimate of time-to-progression (TTP) by randomised allocation suggested that patients with an EORTC global QoL score greater than median (ie better QoL) at randomisation and who received ASCT2 had a significant TTP advantage over those receiving NTC (HR 0.3 (95% CI 0.15-0.61), p=0.006). However, with multivariate Cox regression analysis accounting for stratification factors this difference was not significant. Patients who reported a lower (ie better) than median level of concern on the Side-effects of treatment subscale and who received ASCT2 had a significant TTP advantage over those receiving NTC (Kaplan-Meier HR 0.24 (95% CI (0.10-0.55), p=0.003). This survival difference was still observed after multivariate Cox regression analysis (HR 5.02 (95% CI 1.00-25.20), p= 0.0499). We tested for genomic associations of SNPs from key genes reported to be involved in pain perception and analgesic responsiveness, and subjective outcomes. There were no significant associations for the opioid mu-receptor (OPRM1) and pain or QoL. However, the rs2236861 SNP in the opioid delta-receptor (OPRD1) showed nominally significant associations with worst pain (p=0.022), average pain (p=0.03) and pain interference (p=0.02) at baseline. The rs1045642 SNP in the ABCB1 drug transporter gene was nominally associated with worst pain (p=0.047) and average pain (p=0.019) after bortezomib-based induction therapy. A SNP rs13361160 in the chaperonin CCT5 gene was associated with worst pain (p=0.033), least pain (p=0.006) and pain interference (p=0.03). It was also associated with self-reported global QoL (P=0.014). Conclusions. We report the first PROs using self-reported QoL and pain assessments in myeloma patients having salvage ASCT or NTC. Global QoL was worse and side-effects of treatment higher after ASCT2 for up to 6 months post-randomisation but then equalised. Pain caused less interference with daily living after NTC but became more severe at 2 years, possibly associated with relapse. Patients who reported lower concerns about side-effects of treatment after ASCT2 had a significant TTP advantage. The genomic analyses suggest a potential inherited predisposition that influences both pain and quality of life and warrants further exploration. Disclosures Ahmedzai: Mundipharma: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Grunenthal: Consultancy, Research Funding, Speakers Bureau. Snowden:Sanofi: Consultancy; MSD: Consultancy, Other: Educational support, Speakers Bureau; Janssen: Other: Educational support, Speakers Bureau; Celgene: Other: Educational support, Speakers Bureau. Williams:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Cavenagh:Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Parrish:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Yong:Amgen: Honoraria; Novartis: Consultancy; Takeda: Honoraria; BMS: Honoraria; Janssen: Honoraria; Autolous: Consultancy. Cavet:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Bird:Celgene: Speakers Bureau; Janssen: Other: Educational support; Amgen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Ashcroft:Janssen: Consultancy, Other: Educational support. Brown:Bayer: Research Funding; Roche: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Morris:Celgene: Other: Meeting support; Janssen: Other: Meeting support. Cook:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau.

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Abstract Background & Significance: Prostate cancer (PCa) is the second leading cause of cancer deaths (~34,000 in 2021 (ACS)) in American men. Castration resistance and resistance to the next-gen androgen receptor (AR) targeted drugs are major challenges. Castration resistance involves multiple mechanisms, including androgen-independent signaling by androgen receptor (AR)- or its variants, and lineage plasticity (LP) with AR-indifferent neuroendocrine (NE) differentiation. Identifying new vulnerabilities across these multitude mechanisms could provide new therapeutic avenues against castration-resistant PCa (CRPC). The cell-surface di-ganglioside GD2 is overexpressed in neural crest cell tumors such as neuroblastoma & melanoma and chimeric (Dinutuximab) or humanized (Naxitamab) anti-GD2 antibodies are now FDA-approved for high-risk neuroblastoma therapy. GD2 expression is reported in other cancers such as breast cancer and glioma and is linked to cancer stem cell behavior. While limited prior studies have detected GD2 expression in PCa cell lines or tumor tissues, nothing is known about the functional role of GD2 in PCa. Objectives: We hypothesized that GD2 overexpression in PCa could play a pro-tumorigenic role and that linkage of GD2 overexpression with CRPC progression may reveal the potential of targeting GD2 for CRPC therapy. Study Design & Results: Immunohistochemical analysis of PCa patient and patient-derived xenograft tissue microarrays (TMAs) revealed GD2 expression in a subset of tumor cells. Fluorescence-activated cell sorter analysis of PCa cell lines showed strong constitutive GD2 expression on murine CRPC cell line RM-1 (derived from mutant Ras and c-Myc overexpressing prostatic epithelial cells) and human PCa line 22Rv1 (overexpresses wild-type AR and ARv7 splice variant). GD2 expression was induced de novo upon induction of lineage plasticity in GD2-negative LNCaP C4-2 prostate adenocarcinoma cell line by shRNA knockdown (KD) of RB1 or TP53. High GD2 expression was also induced when C4-2B cells were made enzalutamide resistant (C4-2BER). Induction of GD2 expression correlated with increased expression of rate-limiting GD2 biosynthetic pathway enzyme GD3 synthase (GD3S). CRISPR-Cas9 mediated stable GD3S knockout (KO) in the RM1 cell line led to the loss of GD2 expression. The GD3S-KO RM1 cells exhibited reduced proliferation, migration, invasion, and tumor sphere forming ability compared to the control cells. Intratibial injections in castrated male C57BL/6 mice showed a significant reduction in tumor development by GD3S KO RM1 cells compared to control cells. Conclusions: Our studies demonstrate that GD2 is expressed in a subset of prostate cancers. Cell line-based studies show that GD2 expression promotes pro-tumorigenic traits. Future studies will assess the biological roles of GD2 in PCa and the potential of targeting GD2+ CRPC with antibody-based approved therapeutic agents. Citation Format: Aaqib M. Bhat, Bhopal C. Mohapatra, Insha Mushtaq, Sukanya Chakraborty, Samikshan Dutta, Sameer Mirza, Matthew D. Storck, Subodh M. Lele, Ming-Fong Lin, Bruce J. Trock, Karen S. Sfanos, Colm Morrissey, Eva Corey, Jonathan Melamed, Leah Cook, Kaustubh Datta, Jane Meza, Jawed Siddiqui, Surinder K. Batra, Vimla Band, Hamid Band. Di-ganglioside GD2 expression and role in promoting tumorigenicity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2411.

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Corpus refers to the database of language materials. Cool Edit Pro is a media edit software. This paper explores how to construct spoken language corpus, how to use cool edit pro 2 to make sound wave contrast and give the experimenters an intuitive observation from their own speech waveforms. The key is to offer the obvious waveforms contrast among the sampling waveform of the native speaker, the original and unmodified one of the experimenter and the new waveform of the experimenter after modifications and teachers instructions, which makes the oral autonomic learning more possible and scientific. From long wave or short wave, wave trough or wave crest, smooth wave or sharp wave, the experimenters deviations can be easily identified from the standard during the autonomic practices and efficiently make corrections. Additionally, experimenter also can observe the improvements frequently, which means this experiment more instructive.

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Abstract Abstract 2986 Poster Board II-962 Introduction: The protein C pathway is believed to be a crucial regulator of coagulation. Similar to the adult population, it is of utmost importance in pediatric patients to maintain the balance between pro- and anticoagulatory signals (Petaja and Manco-Johnson 2003). Cancer patients have been shown to have cancer and cancer-therapy associated pathologies of the protein C pathway. (Nijziel, van Oerle et al. 2003; Woodley-Cook, Shin et al. 2006). A test evaluating the response of the protein C pathway after activation of endogenous protein C has been shown to be a sensitive tool to screen for protein C deficiency and APC resistance whereas protein S deficiency is detected less reliably (Toulon, Halbmeyer et al. 2000). This is in line with findings suggesting that any pathology of this assay is related to an increased risk of VTE, independent of the pathology related to the abnormality of the test result (Toulon, Perez et al. 2007). Similarly, patients with idiopathic pregnancy loss were found to have a pathological response independent of the pathology related (Sarig, Lanir et al. 2002). Methods: We therefore evaluated the influence of different variables on the results of the global protein C assay (Pro C Global on a BCS analyzer, Siemens, Marburg, Germany) in 431 children enrolled into the Thrombotect study. The Thrombotect study is a prospective, randomized trial evaluating unfractionated heparin vs low molecular weight heparin vs antithrombin replacement for prevention of thromboembolism in children undergoing asparaginase containing chemotherapy for acute lymphoblasic leukaemia within the BFM protocol. A multivariate linear regression analysis on results obtained before treatment was performed (MedCalc 10.0.1). Results: To date (as of 8/09), 720 children have been randomized in the Thrombotect trial. At the time, we had complete data for laboratory evaluation available for 431 children on day 0 of the treatment protocol. Free protein S, IgG antibodies against cardiolipin or phosphatidlyserine, dRVVT, fibrinogen, the presence of F II G20210A, hom*ocystein concentration, Lp(a) concentration and PAI-1 activity had no predictive value towards the protein C pathway assay result in this multivariate analysis. In contrast, the protein C pathway activity was expectedly shown to be dependent on the presence of the F V Leiden mutation (p<0.0001), protein C activity (p<0.0001) and F VIIIc (p=0.0001). Unexpectedly, the protein C pathway activity was also dependent on antithrombin activity (p=0.0166), F XIIc (p=0.0137) and IgM (but not IgG) antibodies against cardiolipin (p=0.0304) and phosphatidylserine (p=0.0006) in this multivariate analysis. Importantly, the association between protein C pathway activity and the “unexpected” predictors were independent of whether or not the results were in the reference range or not (median [95% CI] antithrombin activity 0.95 [0.93-0.97], median F XIIc 0.94 [0.90-0.98], median ACL IgM 2 [2-3] U/ml, median APS IgM 2 [2-3] U/ml). Conclusions: The protein C pathway is believed to be a crucial regulatory element of haemostasis. Our results from a large cohort (n = 431) of children with ALL and thus at risk for thromboembolism indicate that the protein C pathway is -expectedly (such as F V Leiden mutation, protein C activity, F VIIIc) and unexpectedly (such as antithrombin activity and the concentration of antiphospholipid IgM antibodies) - interdependent with many other variables of the coagulation system. These data provide evidence that the protein C pathway ex vivo in children with ALL is targeted by various elements of other haemostasis pathways in a significant manner in multivariate analysis. Disclosures: No relevant conflicts of interest to declare.

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Nitrite is widespread in the environment, and is frequently used as an additive to extend the shelf life of meat products. However, the excess intake of nitrite can be harmful to human health. Hence, it is very important to know and control the content of nitrite in foodstuffs. In this work, by the means of self-assembly induced by solvent evaporation, we used the amphiphilic PEO-b-PS diblock copolymers resol and cobalt nitrate as a template to synthesize ordered mesoporous CoOx/C nanocomposites. Then, the CoOx/C nanocomposites were modified on a glassy carbon electrode (GCE), which showed excellent sensitivity, good selectivity, and a wide detection range for nitrite. Through cyclic voltammetry and current–time techniques, the electrochemical performance of the GCE modified with CoOx/C nanocomposites was analyzed. Under the optimized conditions, we found that anodic currents were linearly related to nitrite concentrations with a regression equation of lp (µA) = 0.36388 + 0.01616C (R2 = 0.9987) from 0.2 µM to 2500 µM, and the detection limit was 0.05 µM. Furthermore, the electrochemical sensor behaved with high reproducibility and anti-interference ability towards various organic and inorganic ions, such as NO3−, SO42−, Cl−, COOH− (Ac−), Na+, K+, Mg2+, and NH4+. Our results indicated that these CoOx/C nanocomposites could be applied in electrochemical sensors for the rapid and sensitive detection of the food preservative nitrite.

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Trata-se de propor uma simetria entre ao que ocorreu na Baía de Guanabara, no século XVI, entre Tupinambá e franceses e na Baía de Kealakakua, no século XVIII, entre havaianos e ingleses, levando em consideração a dinâmica dos mal-entendidos. Argumenta-se que os brancos foram apreendidos pelos nativos, nos dois casos, de forma análoga, isto é, por meio da predação ontológica.

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Glucose-dependent insulinotropic polypeptide (GIP) is a hormone released from enteroendocrine K cells in response to meals. Posttranslational processing of the precursor protein pro-GIP at residue 65 by proprotein convertase subtilisin/kexin type 1 (PC1/3) in gut K cells gives rise to the established 42-amino-acid form of GIP (GIP1–42). However, the pro-GIP peptide sequence contains a consensus cleavage site for PC2 at residues 52–55 and we identified PC2 immunoreactivity in a subset of K cells, suggesting the potential existence of a COOH-terminal truncated GIP isoform, GIP1–30. Indeed a subset of mouse and human K cells display GIP immunoreactivity with GIP antibodies directed to the mid portion of the peptide, but not with a COOH-terminal-directed GIP antibody, indicative of the presence of a truncated form of GIP. This population of cells represents ∼5–15% of the total GIP-immunoreactive cells in mice, depending on the region of intestine, and is virtually absent in mice lacking PC2. Amidated GIP1–30 and GIP1–42 have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP1–30 represents a naturally occurring, biologically active form of GIP.

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Objetivos: Conocer las propiedades psicométricas de la Escala de Satisfacción Laboral de Warr, Cook y Wall, versión en español, en trabajadores de una institución especializada de rehabilitación. Material y métodos: Estudio de tipo psicométrico. Se incluyeron 88 trabajadores a quienes se les aplicó la Escala de Satisfacción General de Warr, Cook y Wall traducida al español y adaptada por Pérez-Bilbao y Fidalgo, compuesta por 15 ítems y 2 subdimensiones: satisfacción intrínseca y extrínseca. Se realizó análisis factorial exploratorio mediante el método de ejes principales. Resultados: los resultados demuestran que la escala de Satisfacción General de Warr, Cook y Wall es válida y confiable para una sola dimensión. Conclusiones: La valoración de la escala de satisfacción general de Warr, Cook y Wall puede hacerse a 3 niveles: general, satisfacción intrínseca y extrínseca. Sin embargo, los resultados demuestran una mayor consistencia con la medida de la satisfacción general.

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Este trabalho teve por objetivo desenvolver tecnologia para produto curado (presunto "cook-in"), com pernis de cordeiros cruza Texel x Corriedale em associação com tratamentos tecnológicos (massagem em "tumbler" e processo "cook-in"). O estudo foi desenvolvido pela EMBRAPA/CPPSUL e Universidade Federal de Santa Maria, RS, Brasil. Após as análises da composição química, a carne foi injetada manualmente com 20 % de salmoura composta por água + gelo 79%, cloreto de sódio 7,52%, condimento para presunto 4,70%, fosfatos 1,97%, sais de cura 1,88%, sacarose 3,38% e glutamato monossódico 0,19 %. Os presuntos foram avaliados quanto à composição química (umidade, proteína, gordura, cinzas, pigmentos totais e pH), parâmetros sensoriais (cor, aroma, sabor, textura e aceitabilidade) e rendimento. Uma das principais características dos presuntos obtidos com pernil de cordeiros cruza Texel x Corriedale foi o baixo conteúdo de gordura associado ao bom rendimento e à excelente aceitabilidade.

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Roger F. Cook. Postcinematic Vision: The Coevolution of Moving-Image Media and the Spectator. Minneapolis: University of Minnesota Press, 2020, 240 pp., $27.00 (paperback) ISBN: 9781517907679.Federico Alvarez Igarzábal. Time and Space in Video Games: A Cognitive-Formalist Approach. Bielefeld: Transcript-Verlag, 2020, 220 pp., $45.00 (paperback), ISBN: 9783837647136.Daniel Reynolds. Media in Mind. Oxford: Oxford University Press, 2019, 224 pp., $38.95 (paperback), ISBN: 9780190872526.Walley, Jonathan. Cinema Expanded. Oxford: Oxford University Press, 2020, 576 pp., $39.95 (paperback), ISBN: 9780190938642.

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El síndrome de Cook fue descrito por primera vez por Cook en 1985. Este se caracteriza por historia familiar de hipoplasia congénita de las uñas de manos en los dígitos 1,2 y 3, ausencia de uñas en los dígitos 4 y 5, braquidactilia del digito 5 de las manos y ausencia de las uñas de los pies. Además, puede existir una hipoplasia o ausencia de las falanges distales en los pies y las manos. La oficina de enfermedades raras, considera este síndrome como una “enfermedad rara”. Presentamos el caso de un recién nacido con anoniquia congénita en ambas manos y pies en el digito 2 asociado a hipoplasia ungueal en dígitos 1 y 3 respetando dígitos 4 y 5. La radiografía de los dedos sin anormalidades. Este caso podría representar una variante del síndrome de Cook o una nueva enfermedad aun no descrita debido a la existencia de una historia familiar importante con similares deformidades integrantesd de la familia

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The objective of the present work was to optimize concentration of cryoprotectants ethylene glycol (EG) and dimethyl sulphoxide (DMSO) to facilitate the vitrification of buffalo embryos produced by somatic cell nuclear transfer (SCNT). Cloned embryos were produced according to standardized protocols of our laboratory using handmade cloning (Shah et al. 2008). Three different concentrations of EG and DMSO (7.5, 10 and 15%, having 0.5 M sucrose in TCM-199 containing 20% serum) were selected in combination for vitrification of cloned blastocysts in French ministraws (0.25 mL). The numbers of cloned blastocysts vitrified for each concentration were 51, 51 and 52, respectively. The post-thaw viability was accessed by re-expansion rate of blastocysts after culturing in RVCL media (K-RVCL-50, Cook® Australia, Queensland, Australia) for 18 to 24 h. On the basis of re-expansion rate, there was no significant effect of any selected concentrations (7.5, 10 and 15%) on post-thaw viability (25.33 ± 2.43%, 29.00 ± 2.52% and 30.83 ± 3.01%, respectively; P > 0.05). The effect of vitrification on apoptosis level was checked after 18 to 24 h post-thaw by TUNEL assay and the apoptosis index was calculated by dividing the total number of nuclei with DNA-fragmented positive nuclei of the respective blastocyst. We found that, 7.5%-group embryos resulted with a significantly higher apoptotic index (8.28 ± 0.57) than that of the 10 and 15% groups (5.09 ± 0.46 and 4.28 ± 0.24, respectively; P < 0.05). These results clearly indicate that a lower concentration of cryoprotectants (7.5%) increased the chance of apoptosis in blastocysts that were frozen-thawed. The quantitative expression of apoptosis-related genes (Bax, Bid, Mcl-1 and Bcl-xl) in all 3 treatment groups and fresh control embryos were determined by RT-qPCR. Three replications were performed and the mRNA level of each sample was normalized to that of glyceride-3-phosphate dehydrogenase mRNA level. Results of RT-qPCR were analysed using the 2–ΔΔCT method to compare the relative transcriptional levels of the target genes in each group. The RT-qPCR data revealed that the 7.5% vitrified group embryos possessed high expression of pro-apoptotic genes (Bax and Bid) and lower expression of anti-apoptotic genes (Mcl-1 and Bcl-xl) in comparison to the 10 and 15% groups. However, there was no significant change in gene expression between the 10 or 15% groups in comparison with fresh non-vitrified embryos. Our results conclude that the best choice is to use 10 or 15% EG and DMSO cryoprotectants for in-straw zona-free cloned buffalo embryo vitrification. However, further experiments are needed to enhance survival after vitrification. This work was supported by research grants from the National Agriculture Innovative Project (1(5)/2007-NAIP-2) to S. K. Singla.

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Women, especially those already married, usually will manage most household chores, including cooking. However, more significant percentage of married women have worked for a living in addition to doing household chores now [1]. Due to the long hours of working, it is hard for the women to frequently prepare meals at home, resulting in a lower quality of nutrient intake. The convenience meals, fast food, and other foods cooked outside the house are linked with a significantly greater calorie, sodium, and fat intake and a poorer intake of micronutrients [2]. This cross-sectional study aims to determine the association between home cooking frequency and nutrient intake adequacy among working women in Malaysia. A total of 131 working women in Malaysia aged 18 to 60 were recruited using a convenience sampling method after excluding 9 participants due to the underreported dietary intake. The participants must answer the questionnaire regarding the frequency of cooking at home in a week. The nutrient intake is determined based on the 24-hours dietary recall and analyzed using Nutritionist Pro™ version 5.4.0 software. The participants were able to track their daily nutrient intake and home cooking frequency within a week. The participants (median age: 27.0 ± 17 years) were aged between 18 to 60 years old, predominantly married (51.1%), Malay (96.9%), and full-time workers (92.4%), with monthly income for most of the participants (78.6%) are ≤ RM 4 850. Also, 52% of the participants work in the government sector and most current work at Terengganu (48.1%). Also, the majority of the participants do not have any children below 18 years old (70.2%). Most of them live together with their husband and children (41.2%), followed by parents (29%). Most participants reported that they only tended to cook at home between zero to twice a week. Nevertheless, this study indicates that the median energy consumption is somewhat lower, at 1362 kcal, compared to the median energy intake of women from the 2014 Malaysian Adult Nutrition Survey (MANS), which is 1445 kcal [3]. More than half of the individuals (54.2 %) had a poor diet, with scores of less than 51. To conclude, from this study, it is reported that most working women do not get a proper nutrient intake due to the long working hours and other responsibilities. This study revealed that adequate nutritional intake differed considerably between working women who regularly cooked throughout the week and those who did not. Understanding healthy food and ingredient selection along with healthy preparation may improve dietary habits while cooking food at home. Hence, simply devoting time to cooking food at home may not result in a healthy diet since other variables such as socioeconomic position, attitudes, and family preparation abilities may impact diet quality.

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Abstract BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) involves the peripheral blood (PB) expansion of progeny of a hematopoietic stem or progenitor cell that is somatically mutated in a hematological cancer-associated gene (most often TET2 or DNMT3A). CHIP associates with comorbid diseases of aging such as cardiovascular disease. Murine knockout (Tet2 or Dnmt3a) and engraftment models of CHIP develop exacerbated cardiovascular disease and their mutated myeloid cells are more reactive to inflammatory stimuli. However, whether blood leukocytes in human CHIP are hyper-inflammatory remains speculative. We recently found people with CHIP have higher serum levels of certain pro-inflammatory cytokines and chemokines than controls (Cook et al, ASH 2017). Thus, we hypothesized that PB effector cells in people with CHIP will be enriched for pro-inflammatory gene expression and pathways. METHODS: The presence of CHIP (variant allele frequency, VAF>0.02) was determined in the whole PB of 30 hematologically healthy adults >65 years old at Baycrest and Sunnybrook Health Sciences Centers (Toronto, Canada) using Ion Proton DNA sequencing targeting 48 commonly mutated genes in myeloid neoplasms. RNA-Seq (HISeq 4000, Illumina, 75bp paired-end sequencing reads with a depth of >50 million/sample) was performed on corresponding ribo-depleted whole PB samples (PAXgene), reads were aligned with HISAT2, gene counts quantified with featureCount, and analyzed with DESeq2. FDR<0.1 was used as a cutoff for differential gene expression analyses. Correlations with clinical and comorbidity data were tested with logistic regressions. RESULTS: People with CHIP ("CHIP+", n: males=8, females=13; TET2=12, DNMT3A=8, SF3B1=1; VAF range=0.03-0.40) compared to those without CHIP ("CHIP-", n: males=3, females=6) had six significantly downregulated genes (e.g. GZMM) and 10 upregulated genes (e.g. DEFA4, LTF, MPO, see Figure 1A). Hierarchical clustering of these top genes yielded two groups, one consisting of most of the CHIP- cases (8/9 cases, in a cluster of 11, see Figure 1A). The three CHIP+ cases that clustered with CHIP- had VAFs lower than 0.15. Of the 16 differentially regulated genes between CHIP+ and CHIP-, nine were recognized by reactome, and most overlapped (≥6 genes) with pathways involving neutrophil degranulation and innate immunity (Figure 1B). DEFA4, LTF, CRISP3, BPI and MPO specifically encode components of neutrophil granules, with various anti-microbial and homeostatic functions. However, mean neutrophil counts (4.6±1.6 vs. 4.4±1.6 10^9/L for CHIP+ vs. CHIP-) and neutrophil to lymphocyte ratios (3.2±1.4 vs. 2.8±2.1 in CHIP+ vs. CHIP-) did not significantly differ between the groups. This suggests that mutations of CHIP may affect neutrophil/immune-related function or phenotype, potentially contributing to comorbid disease. For example, greater expression of alpha-defensins (i.e. DEFA4) in CHIP may involve dysregulated granulocyte maturation and inflammatory function as seen in myelodysplasia (Droin et al, 2010 Blood), suggesting a potential dysregulation of inflammation and immunity. Higher VAFs (>0.15) associated with higher ECOG scores (poorer overall daily functioning: odds ratio=44, 95% CI=4-500, p=0.002), suggesting that larger proportions of mutated cells may have greater effects on gene expression profiles. Accordingly, there were linear correlations between the VAFs of the mutated cell populations and the levels of differentially expressed genes (Figure 1C). CONCLUSIONS: The connection between mutant clones of CHIP and disease remains poorly elucidated. For the first time, to our knowledge, we studied gene expression in CHIP leukocytes. We report that the most prominent gene expression differences between people with CHIP and those without CHIP involve neutrophil degranulation and the innate immune system. Additionally, higher VAFs may have a greater influence on gene expression levels and health than lower VAFs. We plan to validate these candidate genes in a larger cohort. These novel data warrant further investigation of the cellular pathways perturbed by somatic mutations of CHIP. Disclosures Buckstein: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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A partir das informações etnográficas das gravuras dos cronistas europeus dos séculos XVI e XVII, é possível demonstrar, por meio da analogia etnográfica, que a cerâmica arqueológica da denominada Tradição Tupiguarani, encontrada no litoral leste e nordeste do Brasil, foi produzida pelos Tupinambá. Usando os textos dos cronistas que descrevem a alimentação destes Tupinambá, foi possível também reconstituir a funcionalidade das vasilhas encontradas.

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<p>En octubre de 1991 Enric Miralles conoció su primera promoción de estudiantes de la Staedelschule. Éramos un grupo de doce alumnos internacionales seleccionados por el profesor Peter Cook para pasar un año trabajando sobre diferentes temas elegidos por nosotros mismos, en torno a un proyecto común. Poco antes de que comenzara el semestre, Cook regresó a Londres como decano de la Bartlett School of Architecture y fue Miralles el elegido como profesor de este grupo de estudiantes de arquitectura. El siguiente texto relata la experiencia de un aprendizaje único acontecido ese año.</p>

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To determine whether or not rat plasma inactive renin is prorenin, specific antibodies were raised against two 15-amino acid peptides, Pro-NH2 and Pro-COOH, which contained the NH2-terminal and COOH-terminal sequences, respectively, of the prosegment of rat prorenin. Inactive renin was measured after trypsin treatment. Immunoaffinity chromatography of normal rat plasma on anti-Pro-NH2 and anti-Pro-COOH immunoglobulin G (IgG)-Sepharose showed that about one-half the amount of inactive renin was prorenin, whereas the rest was neither prorenin nor renin. Thus trypsin treatment of the unfractionated plasma does not provide measurement of the concentration of prorenin. However, fractionation of plasma by high-performance liquid chromatography on G3,000SW columns followed by trypsin treatment led to the measurement of prorenin. Prorenin and active renin concentrations in the normal plasma of conscious rats were 44.3 +/- 5.8 and 13.3 +/- 1.4 (SE) ng ANG I.h-1.ml-1, respectively (n = 10). On the other hand, plasma inactive renin from rats at 24 h after bilateral nephrectomy bound to neither anti-Pro-NH2 nor anti-Pro-COOH IgG immunoaffinity columns, and the enzymatic activity after trypsin treatment was not inhibited by anti-mature renin IgG. These results demonstrate that inactive renin from nephrectomized rats was not prorenin. Thus the kidney is the primary source of circulating prorenin in rats.

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O Museu Arqueológico de São Miguel de Odrinhas é depositário de três sarcófa*gos etruscos, que se saiba, os únicos existentes em Portugal. Datados do século IV e III a.C., os sarcófa*gos foram adquiridos no século XIX por Sir Francis Cook, então proprietário da Quinta de Monserrate, na serra de Sintra. Sir Cook utilizou‑os como elementos decorativos nos jardins do seu palácio, testemunhando assim o gosto que a Europa culta do Romantismo nutria por antiguidades e obras de arte de povos antigos e exóticos. Ali permaneceram, tendo sofrido vários danos por parte de visitantes menos esclarecidos e das intempéries naturais. A tampa com estátua jacente de um deles desapareceu numa noite de tempestade, em 1983. Mais tarde, conseguiu‑se a remoção destes monumentos para o Museu Arqueológico de São Miguel de Odrinhas. No presente artigo, propomos a sua análise iconográfica e cronológica.

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Com uso dos conceitos da semiótica greimasiana, este artigo analisa o vídeo institucional presente no site da marca Pantys, tendo o intuito de identificar o discurso desta por meio de uma de suas manifestações. Utilizou-se dos níveis do percurso gerativo do sentido para realizar a análise, bem como das categorias do plano da expressão e o semissimbolismo.

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In United States–Certain Country of Origin Labeling Requirements1the Appellate Body (AB) of the World Trade Organization (WTO) ruled that the United States’ country-of-origin labeling regulations (COOL) on beef and pork products violated the Agreement on Technical Barriers to Trade’s (TBT) National Treatment (NT) Principle.2 Aimed at promoting informed consumer choice, COOL required retailers to disclose the covered products’ origin. In prior decisions under the General Agreement on Tariffs and Trade (GATT) Article III:4, the AB correctly rejected protectionist rules that unnecessarily encumbered consumer choice, while adversely affecting conditions of competition for imports. In US–COOL, however, the AB formalistically transposed such GATT jurisprudence into TBT analysis, equating private action in compliance with neutral, transparency-promoting labeling rules to private action in compliance with capricious, opacity-inducing distribution rules. This article argues that, while GATT NT-jurisprudence should enlighten analysis under the TBT, WTO adjudicators should not allow exporting Members’ perceived entitlement to trade volumes – which may well be premised on continued opacity and uninformed consumer choice – to interfere with importing Members’ origin-neutral regulations. (JEL: F13, F53, K23, K41, Q13, Q17).

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Purpose The purpose of this paper is to present a conceptual framework of cool for social marketing through a comprehensive literature review and integrating extant literature on cool. Design/methodology/approach A comprehensive search and review of extant literature across social marketing, business disciplines, arts, psychology, social sciences and humanities was undertaken to develop an understanding of cool and its relevance to social marketing. The review permitted developing a comprehensive set of characteristics that are associated with cool. Findings A conceptual framework of cool organised according to the following dimensions is presented and discussed: deviating from norm, self-expressive, indicative of maturity, subversive, pro-social, evasive, and attractive. Originality/value This paper advances theoretical knowledge in the social marketing domain by offering a conceptual framework of cool, and by suggesting a set of guidelines to develop cool social marketing programs.

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Abstract Liver metastasis carries a poor prognosis, specifically due to impaired transport of chemotherapies into the lesions causing insufficient drug accumulation which leads to poor treatment response. The tumor immune microenvironment (TIME), especially macrophages which constitute about 10% of total population in the liver, has been recognized as a major factor in supporting tumor growth and affecting therapeutic outcomes. Repolarization of pro- tumorigenic macrophages to anti-tumorigenic M1 macrophages has proven to be a promising new immunotherapy approach. We have created a lipid nanoparticle (LNP) platform capable of delivering a Cas12a/RICTOR-crRNA complex to macrophages to genetically block their differentiation to an M2 phenotype. The particle consists of a mix of phospholipid materials that encapsulates the CRISPR complex and is generated through hydration/extrusion. The resulting biocompatible nanocarriers are around 130 nm, -9 mV zeta potential, and have an encapsulation efficiency of &gt;80%. We administered the CRISPR-LNP via intravenous injection on a syngeneic liver metastasis mouse model. Single- and multi-dose studies were conducted to determine biodistribution, efficacy, and survivability. Lastly, a digital pathology analysis of immunohistochemical images allowed for investigation of the in situ interactions amongst immune and tumor cells within the TIME. Biodistribution data of our rhodamine-lipid-tagged LNP from IVIS imaging and organ hom*ogenate analysis showed that between 1- and 24-hours post-injection, the LNP was predominantly distributed to the liver. The amount of LNP peaked in the liver at around 1 hour post-injection, and by 4 hours the LNP had largely cleared the body. However, signal from the hom*ogenization of isolated tumor metastases remained steady over time despite the decline in the liver signal. Furthermore, intravital microscopy analysis showed rhodamine signal isolated within tumor sites after 24 hours despite the lack of proper vascularization, suggesting the macrophage’s ability to take up particles and infiltrate hypovascularized tumor regions. IHC analysis of liver sections using CD80, CD206, and F4/80 markers showed an increase in M1:M2 ratio following LNP administration when compared to control. Digital pathology analysis on IHC and Imaging Mass Cytometry data showed a decrease in Ki67 expression in 4T1 cells as well as an increased number of immune cells, in particular macrophages, CD8+ and CD8+/PD1+ T-cells. Our results show that reprograming macrophages is a powerful tool to suppress cancer cell growth and increase the presence of cytotoxic CD8+ T- cells. Thus, we hypothesize that this therapy can potentially be administered alongside current leading immunotherapies to obtain synergistic effects. We are currently conducting multi-dose efficacy and survival studies, and aim to combine the CRISPR-LNP treatment with anti PD-1 antibodies to observe their efficacy to protect against resistance. Ultimately, this novel CRISPR vehicle has applications to other cancers with similar molecular/inflammation signature. Citation Format: Tyler Galbraith, Harlan Cook, Arturas Ziemys, Fransisca Leonard. CRISPR lipid nanoparticle modulates the tumor immune microenvironment of liver metastases by genetically eliminating M2 polarization pathway in macrophages [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PR04.

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Atualmente, o ambiente globalizado e altamente competitivo impõe as empresas produtoras de frango dois grandes desafios: a otimização de recursos e a redução dos custos. Neste contexto, este trabalho tem por objetivo implementar modelos de redes neurais artificiais e regressão linear múltipla para análise e previsão de variáveis produtivas de frangos de corte. Analisa-se também, a aplicabilidade de redes neurais recorrentes na previsão do preço do quilo do frango congelado e resfriado. A base de dados disponibilizada pela empresa apresenta um histórico de movimentação de 2 anos, contendo as principais variáveis de produção, para 4500 lotes de aves das linhagens Coob, Coob Fast e Coob Slow. Na análise da aplicabilidade de redes neurais recorrentes utilizou-se um banco de dados de 10 anos fornecido pelo Centro de Estudos Avançado de Economia Aplicada (CEPEA). Os resultados obtidos mostram que os modelos de previsão fornecem estimativas confiáveis para as variáveis de resposta: Peso Médio e Índice de Eficiência Produtiva e demonstram a eficácia das previsões, da rede recorrente LSTM, para o preço do quilo do frango congelado e resfriado, para um horizonte de curto prazo.

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Adsorption of the Glycine–Proline (Gly–Pro) dipeptide has been investigated using surface science complementary techniques on Au(110) and Ag(110), showing some interesting differences both in the chemical form and surface organization of the adsorbed peptide. On Au(110), Gly–Pro mainly adsorbs in neutral form (COOH/NH₂), at low coverage or for a short interaction time; the surface species become zwitterionic at a higher coverage or longer interaction time. These changes are accompanied by a complete reorganization of the molecules at the surface. On Ag(110), only anionic molecules (COO⁻/NH₂) were detected on the surface and only one type of arrangement was observed. These results will be compared to some previously obtained on Cu(110), thus providing a unique comparison of the adsorption of the same di-peptide on three different metal surfaces; the great influence of the substrate on both the chemical form and the arrangement of adsorbed di-peptides was made clear.

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In maturing sperm of the winter flounder, histones are not replaced by protamines but instead joined by a group of high molecular weight basic nuclear proteins. Despite their large size and number of components, these proteins were reduced to a relatively simple set of peptides by a "limit" digestion with endoprotease Lys-C. Nine of these peptides, that together account for half of the mass of the digest, were purified by two rounds of chromatography on a C18 reverse-phase high pressure liquid chromatographic column and analysed by sequential Edman degradation. Their sequences can be divided into two hom*ology groups. Seven of the peptides contain all or part of a dodecapeptide consensus sequence, NH2-Ser-Pro-Met-Arg-Ser-Arg-Ser-Pro-Ser-Arg-Ser-Lys-COOH, which appears to be tandemly repeated. This dodecapeptide contains a previously recognized consensus phosphorylation sequence, NH2-Arg-Ser-Arg-Ser-Pro-COOH, in which both serines are phosphorylated during the early stages of spermiogenesis. The other hom*ology group has the sequence NH2-Arg-Arg-Val-X-X-Pro-Lys-COOH, where X-X is either Gln-Thr or Pro-Ser. The dodecapeptide and heptapeptide sequences form at least 35 and 11%, respectively, of the high molecular weight basic nuclear proteins and are, therefore, repeated many times over in these proteins. A search for identical or hom*ologous sequences within the Protein Sequence Database indicated that they are unique. The closest matches were to protamines and some viral DNA-binding proteins.

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A ocorrência de ureteres ectópicos é pouco frequente e mais observada em cadelas, que apresentam incontinência urinária desde filhotes. Gatos são raramente afetados por essas duas anormalidades de desenvolvimento. Este relato visa apresentar o caso de um gato macho Maine Coon, de um ano e quatro meses, com diagnóstico de ureteres ectópicos bilaterais, hidronefrose unilateral, além de criptorquidismo unilateral. O paciente foi encaminhado devido à queixa de apatia e hiporexia após orquiectomia unilateral realizada alguns dias antes e não apresentava incontinência urinária. O ureter ectópico e a hidronefrose direitos e testículo ectópico esquerdo foram observados por meio de ultrassonografia, enquanto a ectopia do ureter esquerdo foi observada no período transcirúrgico. Optou-se por fazer nefroureterectomia total direita e orquiectomia esquerda naquele momento, além de debridamento de ferida cirúrgica devido a inúmeros abscessos subcutâneos provenientes da primeira cirurgia realizada. Entretanto, 10 horas pós-cirurgia o paciente teve hipotensão e, mesmo após restabelecimento da pressão arterial, veio a óbito. A tutora não autorizou a realização da necropsia para que se pudesse investigar a causa definitiva da morte.

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This research study reports the development of chitosan/carboxylated graphene oxide (CS/GO-COOH) composite scaffolds with nanofibrous architecture using the electrospinning method. The concept of designed composite fibrous material is based on bringing together the biological properties of CS, mechanical, electrical, and biological characteristics of GO-COOH with the versatility and efficiency of ultra-modern electrospinning techniques. Three different concentrations of GO-COOH were added into a chitosan (CS)-poly(ethylene oxide) (PEO) solution (the ratio between CS/PEO was 3/7 (w/w)) and were used in the synthesis process of composite scaffolds. The effect of GO-COOH concentration on the spinnability, morphological and mechanical features, wettability, and biological properties of engineered fibrous scaffolds was thoroughly investigated. FTIR results revealed the non-covalent and covalent interactions that could take place between the system’s components. The SEM micrographs highlighted the nanofibrous architecture of scaffolds, and the presence of GO-COOH sheets along the composite CS/GO-COOH nanofibers. The size distribution graphs showed a decreasing trend in the mean diameter of composite nanofibers with the increase in GO-COOH content, from 141.40 nm for CS/PG 0.1% to 119.88 nm for CS/PG 0.5%. The dispersion of GO-COOH led to composite scaffolds with increased elasticity; the Young’s modulus of CS/PG 0.5% (84 ± 4.71 MPa) was 7.5-fold lower as compared to CS/PEO (662 ± 15.18 MPa, p < 0.0001). Contact angle measurements showed that both GO-COOH content and crosslinking step influenced the surface wettability of scaffolds, leading to materials with ~1.25-fold higher hydrophobicity. The in vitro cytocompatibility assessment showed that the designed nanofibrous scaffolds showed a reasonable cellular proliferation level after 72 h of contact with the fibroblast cells.

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Abstract:

Abstract The blood coagulation cascade is initiated at the site of vascular injury and results in the activation of prothrombin (Pro) to thrombin by the prothrombinase (IIase) complex. IIase is composed of the enzyme, factor Xa (fXa) bound to its cofactor, factor Va (fVa) on a phospholipid surface in the presence of Ca2+ ions. Two pathways for Pro activation are possible: membrane-bound fXa alone activates Pro following initial cleavage at Arg271 followed by cleavage at Arg320, while the fully assembled IIase activates Pro following the opposite pathway, initial cleavage at Arg320 followed by cleavage at Arg271. Activation of Pro via this latter pathway is characterized by the generation of a transient intermediate, meizothrombin (MzT) that has proteolytic activity. Initial cleavage of prothrombin at Arg320 resulting in MzT generation is absolutely fVa-dependent. Human factor V (fV) is activated by thrombin to produce a heterodimer consisting of a heavy chain and a light chain associated through divalent metal ions. The heavy chain of fVa contains an acidic hirudin-like region at the COOH-terminus (amino acids 680–709). We have shown using overlapping peptides from this region that a pentapeptide with the sequence DYDYQ inhibits Pro activation by IIase by inhibiting MzT generation. In has been reported that various proteases can cleave the acidic region of fVa heavy chain to produce a cofactor with a truncated heavy chain. All the studies revealed that removal of the acidic COOH-terminal portion of fVa heavy chain results in a cofactor molecule that is deficient in its clotting activity in a clotting assay using fV-deficient plasma, however IIase assembled with cofactor molecules missing the acidic COOH-terminus have significant higher kcat for Pro activation as assessed in an assay using purified reagents and a chromogenic substrate specific for thrombin. A molecular explanation for these paradoxical observations has not yet been provided. We have created a mutant recombinant fV molecule that is missing the last 30 amino acids from the heavy chain (fVΔ680-709). The clotting activity of the mutant molecule was impaired as compared to wild type fVa. IIase assembled with fVaΔ680-709 demonstrated a 30–40% increase in the kcat for the activation of Pro. Interstingly, gel electrophoresis revealed a delay in Pro activation with persistence of MzT during activation. Further experiments demonstrated that peptide DYDYQ inhibited MzT formation by IIase assembled with fVaΔ680-709. It has been well established that while MzT has poor clotting activity, its amidolytic activity is considerable increased towards small chromogenic substrates compared to thrombin. A logical explanation that will reconcile all the findings described above is that, the acidic COOH-terminus of fVa heavy chain regulates MzT concentration within IIase during the factor Xa catalyzed Pro activation. Thus, activation of Pro by IIase assembled with a cofactor that is missing the acidic region will result in increased MzT production. This result will be translated by a fVa molecule that is deficient in its clotting activity and produces an increase in kcat when introduced into IIase. In contrast, in the presence of an excess of DYDYQ no MzT is made by IIase resulting in the slow generation of thrombin through the alternative pathway. Our data are consistent with the interpretation that the acidic COOH-terminus of fVa heavy chain contributes a major productive interactive site for Pro within IIase.

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Abstract:

Graphene as a type of novel additive significantly enhanced the tribological performance of blended lubricating oil. However, the dispersibility of graphene with long-term stability in lubricating oil is still a challenge. Chemical modification for graphene, rather than using surfactants, provided a better method to improve the dispersibility of graphene in lubricants. In this study, the equilibrium molecular dynamics (EMD) simulations were carried out to investigate the diffusion behavior of graphene nanoplates in poly-α-olefin (PAO) lubricating oil. The effects of graphene-size, edge-functionalization, temperature, and pressure on the diffusion coefficient were studied. In order to understand the influence of edge-functionalization, three different functional groups were grafted to the edge of graphene nanoplates: COOH, COON(CH3)2, CONH(CH2)8CH3 (termed GO, MG, and AG, respectively). The EMD simulations results demonstrated that the relationships between diffusion coefficient and graphene-size and number of functional groups were linear while the temperature and pressure had a nonlinear influence on the diffusion coefficient. It was found that the larger dimension and more functional groups provided the lower diffusion coefficient. AG with eight CONH(CH2)8CH3 groups exhibited the lowest diffusion coefficient. Furthermore, the experimental results and radial distribution function for graphene-PAO illustrated that the diffusion coefficient reflected the dispersibility of nanoparticles in nanofluids to some degree. To our best knowledge, this study is the first time the diffusion behavior of graphene in PAO lubricating oil was investigated using EMD simulations.

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