Articoli di riviste sul tema "Molecular dynamics – Congresses"

The problems and results of research in biophysics, which were devoted to the VII Congress of Biophysicists of Russia (Krasnodar, April 17-23, 2023, http://rusbiophysics.ru/db/conf.pl), are discussed. The results of fundamental and applied research in the field of molecular biophysics, cell biophysics, biophysics of complex multicomponent systems were presented at plenary, sectional and poster sessions. The structure and dynamics of biopolymers, the fundamental mechanisms underlying the impact of physicochemical factors on biological systems, membrane and transport processes were actively discussed. Much attention was paid to new experimental methods of biophysical research, methods of bioinformatics, computer and mathematical modeling as essential research tools at all levels of organization of living systems. Along with the fundamental problems of studying the biophysical mechanisms of regulation of processes at the molecular, subcellular and cellular levels, much attention was paid to applied research in the field of biotechnology and environmental monitoring. Works in the field of medical biophysics were especially widely represented. During the Congress, the National Council for Biophysics was formed.

Herein, we profile the first embryonic mitosis in a hybrid of wheat and maize by using a whole-mount genomic in situ hybridization method and immunofluorescence staining with a tubulin-specific antibody. We have successfully captured the dynamics of each set of parental chromosomes in the first zygotic division of the hybrid embryo 24-28 h after crossing. During the first zygotic metaphase, although both sets of parental chromosomes congressed into the equatorial plate of the zygote, the maize chromosomes tended to lag in comparison with the wheat chromosomes. During anaphase, each parental chromosome separated into its sister chromosomes; however, some of the maize chromosomes lagged around the metaphase plate as segregants. The maize sister chromosomes that did move toward the pole showed delayed and asymmetric movement as compared with the wheat ones. Immunological staining of tubulin revealed a bipolar spindle structure in the first zygotic metaphase. The kinetochores of the maize chromosomes that lagged around the metaphase plate did not attach to the spindle microtubules. These results suggest that factors on the kinetochores of maize chromosomes that are required to control chromosome movement are deficient in the zygotic cell cycle.Key words: whole-mount, GISH, chromosome elimination, hybrid embryogenesis.

Abstract Detection and monitoring of minimal residual disease (MRD) in APL patients has become a routine practice and is essentially important for tailoring the therapeutical intervention. Two major isoforms of PML-RARa fusion gene (bcr1/2 and bcr3) are considered to determine diverse outcome with bcr3 to be less favorable. It was also shown by different study groups that among different ethnic populations the ratio of bcr1/2 and bcr3 varies. The prevalence of bcr1/2 isoform over bcr3 was reported in Latinos and Chinese population: 84% vs 16% and 73% vs 27%, respectively. Less evident but nevertheless convincing tendency was registered in USA (US Intergroup – 63% vs 37%; Memorial Sloan Kettering CRC – 66% vs 34%), Great Britain (MRC – 61% vs 39%), Italy (GIMEMA – 60% vs 40%), Spain (PETHEMA – 56% vs 44%) (Santillana S. et al Joint International Congress on APL, Rome, 2001, abstr P2.14; Dan Douer et al BJH, 2003, p.563–570). The analysis of PML-RARa transcript in 66 APL patients included in the Russian Multicenter trial revealed the inverse (statistically significant from mentioned above) ratio with 37 patients (56%) bearing bcr3 isoform and 29 (44%) – bcr1/2. There is no exact explanation for these findings but it may be due to low numbers of cases and perhaps to certain environmental and/or ethnic reasons. The treatment results in these 66 APL patients are very similar to usually reported with 7+3+ATRA protocols – 91% CR rate with 75% molecular CR after the first and 96% - after the second course. The OS and DFS do not differ according to the isoform and constitute 77% and 80% at 3 years, respectively. It is worth to stress that close monitoring of MRD (3–15 probes per patient) revealed different time adjusted dynamics in the molecular relapse incidence for bcr1/2 and bcr3 isoform. It was equal at each month during the whole period of follow-up (36 mo from treatment start) for bcr1/2 patients, and clustered in two periods (3–12 mo) and (20–36 mo) for bcr3 patients with 8 months of absence of positive signal. So we may suppose that each isoform of PML-RARa fusion gene determines its distinctive course of MRD while standard APL treatment. This data once again shows discrepancies in the biological features of APL with bcr1/2 and bcr3 isoforms.

The 30th Congress of the International Union of Game Biologists (IUGB) and Perdix XIII was held at the ‘Hotel Juan Carlos I’ in Barcelona, Spain, from 5 to 9 September 2011. The event was organised by the University of Barcelona, the Regional Government of Catalonia Department of Agriculture, Farming, Fish, Food and Environment, the Spanish Institute of Game Resources Research (IREC), and the British Game and Wildlife Conservation Trust. Every two years since the mid–1950s, the International Union of Game Biologists (IUGB) has brought together international wildlife biologists, forestry scientists, veterinarians, game managers, hunters and others with an interest in game or wildlife biology. The IUGB encourages the exchange of scientific and practical knowledge in the field of game and wildlife management, the broad field of game biology, and international co–operation in game and wildlife management. The aim of the conference is to build bridges between scientists, wildlife managers and authorities, and those studying the human dimensions of wildlife management. Following the meetings in Limassol (Cyprus) in 2001 and Braga (Portugal) in 2003, Perdix XIII joined the IUGB Congress series for the third time in its history. Founded in the 1960s, the Perdix series has traditionally attracted partridge, quail and francolin researchers and conservationists from across Europe and North America. To make the Perdix series even more attractive to gamebird biologists, specialists in any Galliform species —whether pheasants, cracids, megapodes or grouse— is welcomed. This joint congress provided a forum to share current developments in gamebird and mammal wildlife research and management, offering an excellent opportunity to identify research gaps, to determine conservation action needs, and to co–ordinate research projects. The congress was attended by 397 researchers and wildlife managers from 37 different countries from the five continents, and included many of the world’s leading wildlife biologists. The general topic was ‘Human–wildlife conflicts and peace-building strategies’. The objective was to summarise the general philosophy of the organising and scientific committees to try to overcome the simple collection of problems derived from human–wildlife interactions by proposing solutions on the basis of scientific knowledge of wildlife and management. A total of 260 contributions were presented. Sixty–eight Perdix XIII communications were related to galliform species (38 oral communications and 30 posters). Additionally, keynote plenary lectures were given by renowned experts, each of whom opened one of the eight main topics of the Conference: – First plenary session: ‘Veterinary aspects of wildlife and conservation’ Bushmeat hunting regulates ebola emergence. Speaker: Dr. Peter D. Walsh – Second plenary session: ‘Species extinctions and population dynamics’ Galliform species and species extinctions: what we know and what we need to know. Speaker: Dr. Philip K. J. McGowan Third plenary session: ‘Wildlife law and policy’ Policy responses to human-wildlife conflicts. A perspective from the convention of migratory species (CMS). Speaker: Dr. Borja Heredia – Fourth plenary session: ‘Conservation and management of migratory species’ Conservation and management of the Common quail (Coturnix coturnix) in Europe: past, present and future. Speaker: Dr. Manel Puigcerver – Fifth plenary session: ‘Wildlife biology, behaviour and game species management’ The Grey partridge in the UK: population status, research, policy and prospects . Speaker: Dr. Nicholas Aebischer – Sixth plenary session: ‘Interactions humans–wildlife’ Managing conflicts between conservation and gamebird management. Speaker: Dr. Steve Redpath – Seventh plenary session: ‘Methodologies, models and techniques’ Molecular genetic tools and techniques for improving management of wildlife and game species. Speaker: Dr. Lisette Waits – Eigth plenary session: ‘Human dimensions of game wildlife management’ Sustainable hunting: an exploration along ecological and social dimensions. Speaker: Dr. John Linnell Of these eight lectures, four were clearly focused on Galliformes species and the others were of general interest to the audience. Six specific workshops were also presented during the Conference, three of which were of particular interest to Perdix attendees: – Sustainable management of migratory birds – what may hunters and game biologists expect from each other?, led by Dr. Yves Lecocq and Dr. Conor O’Gorman. – GALLIPYR: Pyrenean Network for the mountain game fowl, led by Dr. Virginie Fabre (geieforespir@forespir.com) and sponsored by the GALLIPYR INTERREG Project. – Reconciling agricultural management, small game production and biodiversity conservation: recommendations for the CAP reform, led by Drs. J. Viñuela, F. Casas, F. Ros, D. Villanúa, P. Ferreras, J. Torres, I. Leranoz, J. Ardaiz, V. Alzaga, A. Cormenzana and E. Castién. Further information can be found on the Conference web page (www.iugb2011.com) where the final programme, the abstract book (in PDF format), and extended abstracts of some contributions can be downloaded. Some of the most outstanding contributions, selected by the scientific committee of the Conference, are now published in this special issue of the international scientific journal Animal Biodiversity and Conservation. We wish to thank the scientific and organising committees, the sponsors, and the participants for making this meeting such an interesting, friendly and highly valuable event.

Abstract Purpose: Drug tolerance has emerged as one of the major mechanisms driving resistance to targeted therapies (TT), but a comprehensive understanding of the dynamics and molecular heterogeneity underlying the adaptive drug response in patients is still lacking. Here, we used iterative liquid biopsies from osimertinib-treated lung cancer patients to monitor and characterize minimal residual disease (MRD) using both circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). Experimental design: LUNG-RESIST (NCT04222335) is a prospective research study enrolling EGFR-mutant adenocarcinoma patients treated by osimertinib frontline. We collected blood samples at baseline, 1 month and every 3 months until progression. CtDNA was used to monitor the initial EGFR mutation (EGFRm) by digital PCR, and to identify new potential biomarkers of resistance by next-generation sequencing (NGS). CTC were enriched and isolated based on their size, absence of leucocyte staining and viability, to perform single-cell transcriptomic and genomic analyses. Results: 40 patients have been enrolled with a median progression-free survival (mPFS) of 14.5 months (95%CI, 8.5-24.5 months). 28/40 (70%) patients had detectable EGFRm in ctDNA at baseline, and decreased ctDNA level could be measured in 25/26 (96%) patients after 1 month of treatment, with a complete clearance in 15/26 (58%) patients. 7/11 (64%) patients without clearance at 1 month relapsed within 9 months. Clinical relapse could be anticipated 3 months ahead based on ctDNA increase for 9/20 (45%) patients. CTC-like cells have been collected at baseline and MRD (between 1 and 3 months) from respectively 31/40 (78%) and 29/40 (73%) patients, and at clinical progression for 12/22 (54%) patients who relapsed, for a total number of 1,510 cells. The number of CTC-like cells decreased after 1 month of treatment in 18/29 (62%) patients, and increased again in 7/12 (58%) patients at the time of clinical relapse. The results of NGS analyses on ctDNA and single-cell transcriptomic and genomic analyses on CTC will be presented at the congress, and should provide a better insight into the dynamics of molecular events occurring throughout the adaptive response in patients. Conclusion: We report the first molecular profiling of both ctDNA and CTC during the adaptive response to osimertinib in lung cancer patients. Monitoring the response and predicting the clinical outcome for EGFR-mutant lung cancer patients undergoing TT treatment can be done using ctDNA level as a biomarker. The isolation of CTC-like cells represents a non-invasive approach to study drug tolerance and ultimately develop new combinatory treatments to prevent relapse. Citation Format: Celia Delahaye, Anne Casanova, Estelle Clermont-Tarenchon, Aurelia Doussine, Juan-Pablo Cerapio, Anaïs Anton, Emma Devienne, Vincent Dongay, Julie Milia, Gilles Favre, Olivier Calvayrac, Anne Pradines, Julien Mazieres. Assessment of minimal residual disease in lung cancer patients treated with osimertinib using liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB094.

ABSTRACTThe human basidiomycetous fungal pathogenCryptococcus neoformansserves as a model fungus to study sexual development and produces infectious propagules, basidiospores, via the sexual cycle. Karyogamy is the process of nuclear fusion and an essential step to complete mating. Therefore, regulation of nuclear fusion is central to understanding sexual development ofC. neoformans. However, our knowledge of karyogamy genes was limited. In this study, using a BLAST search with theSaccharomyces cerevisiae KARgenes, we identified fiveC. neoformanskaryogamy gene orthologs:CnKAR2,CnKAR3,CnKAR4,CnKAR7(orCnSEC66), andCnKAR8. There are no apparent orthologs of theS. cerevisiaegenesScKAR1,ScKAR5, andScKar9inC. neoformans. Karyogamy involves the congression of two nuclei followed by nuclear membrane fusion, which results in diploidization. ScKar7 (or ScSec66) is known to be involved in nuclear membrane fusion. InC. neoformans,kar7mutants display significant defects in hyphal growth and basidiospore chain formation during botha-α opposite and α-α unisexual reproduction. Fluorescent nuclear imaging revealed that duringkar7×kar7bilateral mutant matings, the nuclei congress but fail to fuse in the basidia. These results demonstrate that theKAR7gene plays an integral role in both opposite-sex and unisexual mating, indicating that proper control of nuclear dynamics is important.CnKAR2was found to be essential for viability, and its function in mating is not known. No apparent phenotypes were observed during mating ofkar3,kar4, orkar8mutants, suggesting that the role of these genes may be dispensable forC. neoformansmating, which demonstrates a different evolutionary trajectory for theKARgenes inC. neoformanscompared to those inS. cerevisiae.

In early mitosis, the END (Emi1/NuMA/Dynein-dynactin) network anchors the anaphase-promoting complex/cyclosome (APC/C) to the mitotic spindle and poles. Spindle anchoring restricts APC/C activity, thereby limiting the destruction of spindle-associated cyclin B and ensuring maintenance of spindle integrity. Emi1 binds directly to hypophosphorylated APC/C, linking the APC/C to the spindle via NuMA. However, whether the phosphorylation state of the APC/C is important for its association with the spindle and what kinases and phosphatases are necessary for regulating this event remain unknown. Here, we describe the regulation of APC/C-mitotic spindle pole association by phosphorylation. We find that only hypophosphorylated APC/C associates with microtubule asters, suggesting that phosphatases are important. Indeed, a specific form of PPP2 (CA/R1A/R2B) binds APC/C, and PPP2 activity is necessary for Cdc27 dephosphorylation. Screening by RNA interference, we find that inactivation of CA, R1A, or R2B leads to delocalization of APC/C from spindle poles, early mitotic spindle defects, a failure to congress chromosomes, and decreased levels of cyclin B on the spindle. Consistently, inhibition of cyclin B/Cdk1 activity increased APC/C binding to microtubules. Thus, cyclin B/Cdk1 and PPP2 regulate the dynamic association of APC/C with spindle poles in early mitosis, a step necessary for proper spindle formation.

Power dissipation in electronic devices is projected to increase over the next 10years to the range of 150-250W per chip for high performance applications. One of the primary obstacles to the thermal management of devices operating at such high powers is the thermal resistance between the device and the heat spreader or heat sink that it is attached to. Typically the in situ thermal conductivity of interface materials is in the range of 1-4W∕mK, even though the bulk thermal conductivity of the material may be significantly higher. In an attempt to improve the effective in situ thermal conductivity of interface materials nanoparticles and nanotubes are being considered as a possible addition to such interfaces. This paper presents the results of a numerical study of transport in a thermal interface material that is enhanced with carbon nanotubes. The results from the numerical solution are in excellent agreement with an analytical model (Desai, A., Geer, J., and Sammakia, B., “Models of Steady Heat Conduction in Multiple Cylindrical Domains,” J. Electron. Packaging (to be published)) of the same geometry. Wide ranges of parametric studies were conducted to examine the effects of the thermal conductivity of the different materials, the geometry, and the size of the nanotubes. An estimate of the effective thermal conductivity of the carbon nanotubes was used, obtained from a molecular dynamics analysis (Mahajan, S., Subbarayan, G., Sammakia, B. G., and Jones, W., 2003, Proceedings of the 2003 ASME International Mechanical Engineering Congress and Exposition, Washington, D.C., Nov. 15–21). The numerical analysis was used to estimate the impact of imperfections in the nanotubes upon the overall system performance. Overall the nanotubes are found to significantly improve the thermal performance of the thermal interface material. The results show that varying the diameter of the nanotube and the percentage of area occupied by the nanotubes does not have any significant effect on the total temperature drop.

The traditional method of retrieving atmospheric ducts is to use the special sensor of weather balloons or rocket soundings to obtain information intelligently, and it is very expensive. Today, with the development of technology, it is very convenient to retrieve the atmospheric ducts from Global Navigation Satellite System (GNSS) phase delay and propagation loss observation data, and then the GNSS receiver on the ground forms an automatic receiving sensor. This paper proposes a hybrid decomposition-based multi-objective evolutionary algorithm with adaptive neighborhood sizes (EN-MOEA/ACD-NS), which dynamically imposes some constraints on the objectives. The decomposition-based multi-objective evolutionary algorithm (MOEA/D) updates the solutions through neighboring objectives, the number of which affects the quality of the optimal solution. Properly constraining the optimization objectives can effectively balance the diversity and convergence of the population. The experimental results from the Congress on Evolutionary Computation (CEC) 2009 on test instances with hypervolume (HV), inverted generational distance (IGD), and average Hausdorff distance ∆2 metrics show that the new method performs similarly to the evolutionary algorithm MOEA/ACD-NS, which considers only the dynamic change of the neighborhood sizes. The improved algorithm is applied to the practical problem of jointly retrieving atmospheric ducts with GNSS signals, and its performance further demonstrates its feasibility and practicability.

paper session 29: Molecular biology - forage quality. In: Proc. XVII International Grassland Congress, pp. 1105-6. Keeling and Mundy Ltd., Palmerston North, New Zealand. United States Department of Agriculture. (1980). Report and recommendations on organic farming. U.S. Government Printing Office, Washington, DC. VanTassel, L. W., Heitschmidt, R.K. and Conner, J.R. (1987). Modeling variation in range calf growth under conditions of environmental uncertainty. J. Range. Manage. 40: 310-4. Walker, B.H. (1993). Stability in rangelands: ecology and economics. In: Proc. XW International Grassland Congress, pp. 1885-90. Keeling and Mundy Ltd., Palmerston North, New Zealand. Walker, J.W. (1994). Multispecies grazing: the ecological advantage. Sheep Res. J. Special Issue: 52-64. Walker, A.B., Frizelle, J.A. and Morris, S.D. (1994). The New Zealand policy framework for sustainable agriculture and some implications for animal production research. Proc. N. Z. Soc. Anim Prod. 54: 369-72. Walker, J.W., Heitschmidt, R.K., DeMoraes, E.A., Kothmann, M.M. and Dowhower, S.L. (1989). Quality and botanical composition of cattle diets under rotational and continuous grazing treatments. J. Range Manage . 42: 239-42. Whitson, R.E., Heitschmidt, R.K., Kothmann, M.M. and Lundgren, G.K. (1982). The impact of grazing systems on the magnitude and stability of ranch income in the Rolling Plains of Texas. J. Range Manage .35: 526-32. Wight, J.R. and Hanson, C.L. (1993). Simulation models as decision aids for management of rangeland ecosystems. In: Proc. XVII International Grassland Congress, pp. 770-1. Keeling and Mundy Ltd., Palmerston North, New Zealand. Wilson, A.D., Harrington, G.N. and Beale, I.F. (1984). Grazing management. In: Management of Australia's rangelands (Eds G.N. Harrington, A.D. Wilson and M.D. Young) pp. 129-40. Commonwealth Scientific and Industrial Research Organization, Australia. Wood, W.R. and Thiessen, T.D. (Eds) (1985). Early fur trade on the Northern Plains: the narratives of John Macdonnell, David Thompson, Francois-Antoine Laraocque and Charles McKenzie. University of Oklahoma Press, Norman, Oklahoma. Manuscript received 4 April 1996, accepted 30 July 1996. Rangel. J. 18(2) 1996, 216-43 EVALUATING STOCKING RATE IMPACTS IN RANGELANDS: ANIMALS DON'T PRACTICE WHAT WE PREACH A.J. Ash1 and D.M. Stafford Smith2 'CSIRO Division of Tropical Crops and Pastures, PMB, Aitkenvale, Qld 4814 2CSIR0 Division of Wildlife and Ecology, PO Box 2111, Alice Springs, NT 0871 Abstract Stocking rate is the most important management variable affecting productivity and stability in rangelands. In this paper we examine the relevance of stocking rate research to the complex and highly variable ecosystems that make up most rangeland enterprises. We review a number of stocking rate experiments that have been conducted in both rangelands and more intensively grazed, improved pastures and demonstrate a fundamental difference in the nature of the stocking rate - animal production relationship between the two environments. Animal production in rangelands is less sensitive to increases in utilisation rate than in improved pastures, at least in the short to medium time frame of most experiments. These differences can largely be explained by factors relating to the much greater spatial and temporal variability of rangelands such as: inter-annual and seasonal fluctuations in vegetation composition and quality; long-term vegetation changes; and spatial and temporal patterns of diet selection in complex vegetation. Together, these factors limit the application of linear stocking rate models to complex rangeland environments for prediction of animal production responses. We suggest that dynamic simulation models, which incorporate the spatial and temporal variability of rangelands, may be the best way of developing simple but useful management principles for setting stocking rates that are more appropriate than simplified regression relationships.

For IUPAC, the global, scientific organization that cares about chemistry and the chemical sciences in all senses of the word, it is a duty, but also a pleasure to follow the development in chemical research closely with the aim of spotting pioneering work and new trends as early as possible. In doing so, it became abundantly clear that the young chemists were about to become more important for the future of our science than they were just a decade or so ago. For chemistry, it is therefore important to encourage our young colleagues in their work, and IUPAC does so through the IUPAC Prize for Young Chemists. This prestigious annual prize honors 4-5 chemists with a fresh Ph.D. for exceptional work during their Ph.D. studies. The work is mainly judged on the basis of a 1000-word essay which is supported by recommendations from the senior scientist(s) with whom the candidate collaborated.As immediate Past President of IUPAC, I had the pleasure of chairing an international prize selection committee of eminent chemists with a wide range of expertise in chemistry that adjudicated essays from 49 applicants from 19 countries. To pick the winners was not an easy task, because there were many outstanding candidates, but at the end the committee arrived at a unanimous decision and awarded the 2006 IUPAC Prize to the following young chemists:Michelle Nena Chrétien, University of Ottawa, Ontario, Canada, with a thesis entitled "Photochemical, photophysical, and photobiological studies of zeolite guest–host complexes"Valentina Domenici, University of Pisa, Italy, with a thesis entitled "Structure, orientational order and dynamics of rod-like and banana-shaped liquid crystals by means of 2H NMR: New developments"Matt Law, University of California, Berkeley, CA, USA, with a thesis entitled "Oxide nanowires for sensing, photonics and photovoltaics"Emilio M. Pérez, University of Edinburgh, UK, with a thesis entitled "Hydrogen-bonded synthetic molecular machines"Dunwei Wang, Stanford University, CA, USA, with a thesis entitled "Synthesis and properties of germanium nanowires"Each of the winners will receive both a cash prize of USD 1000 and a free trip to the 41st IUPAC World Chemistry Congress, which will take place in Turin, Italy, 5-11 August 2007. Here the winners will have the opportunity to present their work, which is an important stage of any research project. But to reach an even wider audience, the prizewinners have been invited to submit manuscripts on aspects of their research for publication in Pure and Applied Chemistry. It is therefore a pleasure to see that four refereed papers, containing critical reviews of high quality, appear in this issue of PAC.It is a great pleasure to congratulate each of the winners (and their supervisors) with the 2006 IUPAC Prize. It is IUPAC's hope that each winner is encouraged to continue to do exciting research that will contribute to a bright future for the molecular-based sciences, which are so important for our common future.Leiv K. SydnesIUPAC Immediate Past President and Chairman of the IUPAC Prize Selection Committee

Abstract Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have immunomodulatory properties that may potentiate anti-PD-L1 therapy. To explore this, we developed the academic ARIANES phase 2 basket trial, which evaluated the PARPi rucaparib (R) and the anti-PD-L1 atezolizumab (A) in selected patients (pts). We performed single-cell RNA + T cell receptor sequencing (scRNA+TCR-seq) on 3 sequential tumor biopsies in a pts subset. Methods: ARIANES comprised 4 molecularly-selected DNA damage response deficient (DDRd), 3 platinum-sensitive, and 2 unselected cohorts of pts with non-small cell lung (NSCLC), prostate (CRPC), and other non-breast non-ovarian cancers. R was administered for 3 weeks, followed by R+A. Primary endpoint was overall response rate (ORR) at 12 weeks per cohort. scRNA+TCR-seq was performed on fresh biopsies collected at baseline, on R, and on R + A in the same lesion, with concomitant plasma collection. We tracked the evolution over time of tumor and microenvironment cells, differentially expressed genes and signatures within each cell population, and TCR clonal dynamics. Results: ARIANES enrolled 130 pts, including 27 DDRd CRPC and 3 DDRd NSCLC pts, on which we focus here. Best ORR by RECIST v1.1 was 22% (6/27) in CRPC pts, and mPFS: 7.9 months (95% CI 4 - 11.1) at data cut-off. ORR was 0% in NSCLC pts. We successfully profiled 3 sequential fresh biopsies in 2 BRCA2-mutant CRPC, 1 ATM-mutant, and 1 RAD54L-mutant NSCLC pts. Tumor, T and B lymphoid, myeloid, plasma, dendritic, NK, endothelial, and stromal cells were identified in all samples. Differential expression testing unveiled PARP1 upregulation in tumor cells on R. One CRPC pt with prolonged partial response displayed activation of innate immune sensing pathways (including cGAS-STING and IFN signaling) in tumor and immune cells, as well as JAK/STAT and CCL5, all increasing gradually on R and R + A; scTCR-seq revealed the expansion of specific T cell clonotypes on R + A. One ATM-mutant NSCLC pt with 6-month stable disease displayed increased cGAS/STING, JAK/STAT and CCL5 activation on R in NK cells only, and no TCR expansion. None of the above was observed in the 2 pts who progressed. Complete clinical and translational study results will be presented at the congress. Conclusion: Sequential scRNA+TCR-seq enables the dynamic assessment of tumor and immune cells on therapy. Our data confirms the potential of R to activate innate immune pathways in pt tumors, and R + A to induce T cell activation and clonal expansion. To our knowledge, this is the first study providing a longitudinal single-cell resolution analysis of the clonal evolution of tumor and immune cells in pts on PARPi + anti-PD-L1. We identify potential biological correlates of therapy response, including the activation of innate immune pathways and TCR expansion. Citation Format: Julien Vibert, Clémence Hénon, Lambros Tselikas, Baptiste Bonnet, Arnaud Pagès, Alice Bernard-Tessier, Léo Colmet-Daage, Roman Chabanon, Nicolas Dorvault, Clémence Astier, Anas Gazzah, Aurore Jeanson, Aurélien Parpaleix, Ronan Flippot, Natacha Naoun, Anna Patrikidou, Pernelle Lavaud, Giulia Baciarello, Emeline Colomba, Alina Fuerea, Laurence Albiges, Christophe Massard, Santiago Ponce, Yohann Loriot, Stéphane Champiat, Capucine Baldini, Fanny Bouquet, Nathalie Droin, Karim Fizazi, Damien Vasseur, Patricia Martin-Romano, Etienne Rouleau, Kaïssa Ouali, Sophie Postel-Vinay. Clinical and translational results of the academic ARIANES Phase 2 basket study: Longitudinal single-cell analysis of patient tumors identifies biological correlates of response to PARP inhibitors and anti-PD-L1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6406.

IUPAC is a global, scientific organization that contributes to the worldwide understanding of chemistry and the chemical sciences. It is certainly true that young chemists are shaping our science, and it is important for IUPAC to provide encouragement to our young colleagues. IUPAC accomplishes this goal through the IUPAC Prize for Young Chemists. This prestigious annual prize honors four to five chemists for important and outstanding research carried out during recent Ph.D. studies. The work is mainly judged on the basis of a 1000-word essay which is supported by recommendations from the senior scientist(s) with whom the candidate collaborated.As immediate Past President of IUPAC, I have had the pleasure of chairing an international prize selection committee of eminent chemists with a wide range of expertise in chemistry that adjudicated essays from 42 applicants from 16 countries. Reading these outstanding essays provided a wonderful overview of new trends in chemistry. Due to the large number of excellent candidates, it was not an easy task to pick the winners, but in the end the committee arrived at a unanimous decision and awarded the 2008 IUPAC Prize for Young Chemists to the following five chemists:- Emilie V. Banide, University College Dublin, Dublin, Ireland, with a thesis entitled "From allenes to tetracenes: Syntheses, structures and reactivity of the intermediates"- Christopher Thomas Rodgers, University of Oxford, UK, with a thesis entitled "Magnetic field effects in chemical systems"- Akinori Saeki, Osaka University, Osaka, Japan, with a thesis entitled "Nanometer-scale dynamics of charges generated by radiations in condensed matter"- Andrea Rae Tao, University of California, Berkeley, CA, USA, with a thesis entitled "Nanocrystal assembly for bottom-up plasmonic materials"- Scott Warren, Cornell University, Ithaca, NY, USA, with a thesis entitled "Nanoparticle-block copolymer self-assembly"Each winner received a cash prize of USD 1000 and a trip to the 42nd IUPAC World Chemistry Congress, which will take place in Glascow, Scotland, 2-7 August, 2009. Here the winners will have the opportunity to present their work, which is an important stage of any research project. To reach an even wider audience, the prize winners were invited to submit manuscripts on aspects of their research for publication in Pure and Applied Chemistry (PAC). It is a pleasure to see that all five prize winners have taken advantage of this offer. The result is the five refereed papers which contain critical reviews of high quality and appear in this issue of PAC.Finally, it is an honor and a pleasure to congratulate each of the winners (and their supervisors) for winning the 2008 IUPAC Prize. It is IUPAC's hope that each of them has been encouraged to continue to do exciting research that will contribute to a bright future for the molecular-based sciences, which are so important for our common future.Bryan R. HenryIUPAC Immediate Past President and Chairman of the IUPAC Prize Selection Committee

e4176066In this paper we present a discussion about the implications of the theory of mental models in the teaching and learning process in Chemistry, with the purpose of discussing the use of stop motion animation as a data collection instrument to investigate the students' mental representations about chemical concepts, especially about their dynamic character. To achieve the objectives mentioned in the present work, we seek to relate the theory of mental models and their implications for the teaching and learning processes in chemistry, with the proposal of the triangulation of the three different representational levels of Chemistry (submicroscopic, symbolic and macroscopic), which are necessary to understand this Science. It is also noteworthy that this articulation was based on the main difficulties associated with the teaching and learning processes in Chemistry and was thought of the particularity involving the dynamics of the atomic-molecular level. The discussions carried out involving the different references used allowed us to discuss the potentialities associated with the use of stop motion as an instrument for investigating mental models on chemical concepts, highlighting the fact that it is a technique that is easy to apply, low cost and that allows the dynamic representation of chemical phenomena considering the submicroscopic level.ResumoNo presente trabalho apresentamos uma discussão acerca das implicações da teoria dos modelos mentais nos processos de ensino e aprendizagem em Química, com a finalidade de discorrer sobre o uso de animação em stop motion como um instrumento de coleta de dados para se investigar as representações mentais dos sujeitos sobre conceitos químicos, em especial sobre seu caráter dinâmico. Para atingir os objetivos mencionados no presente trabalho, buscamos relacionar a teoria dos modelos mentais e suas implicações para os processos de ensino e aprendizagem em Química, com a proposta da triangulação dos três diferentes níveis representacionais da Química (submicroscópico, simbólico e macroscópico), que são necessários para a compreensão dessa Ciência. Destacamos também, que tal articulação foi pautada nas principais dificuldades associadas aos processos de ensino e aprendizagem em Química e pensada na particularidade envolvendo a dinamicidade do nível atômico-molecular. As discussões realizadas envolvendo os diferentes referenciais utilizados nos possibilitaram discutir sobre as potencialidades associadas ao uso do stop motion como um instrumento de investigação dos modelos mentais sobre conceitos químicos, em destaque para o fato de se tratar de uma técnica de fácil aplicação, de baixo custo e que permite a representação dinâmica pelos alunos dos fenômenos químicos considerando o nível submicroscópico.Palavras-chave: Pesquisa e Educação, Tecnologia e Educação, Psicologia Cognitiva, Avaliação da Aprendizagem.Keywords: Educational Research, Educational Technology, Cognitive Psychology, Evaluation methods.ReferencesBACHELARD, G. A formação do espírito científico. Rio de Janeiro: Contraponto, 1996.BORGES, A. T. Como evoluem os modelos mentais. Ensaio Pesquisa em Educação em Ciência, Belo Horizonte. v. 1, n.1. jan-jun. 1999. p. 66-92.BUNGE, M. Teoria e realidade. São Paulo: Perspectiva, 1974.CUTRERA, G; STIPCICH, S. El triplete químico. 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Background: Oral decitabine/cedazuridine (ASTX727) is a fixed dose combination of decitabine (35 mg) and the cytidine deaminase inhibitor cedazuridine (100 mg) given once daily X 5 days on a 28-day cycle producing pharmacokinetic (PK) exposure equivalent to the standard intravenous (IV) decitabine regimen of 20 mg/m 2 daily X 5 days on a 28-day cycle. This was demonstrated in the pivotal ASCERTAIN study (Garcia-Manero, et al, ASH 2019) as it provided a PK bridge to existing decitabine data and demonstrated median OS was 31.7 mo. (Savona,et al. Intl. MDSF International Congress on MDS, 2021). Subjects were initially classified by the International Prognosis Scoring System (IPSS) for historical reasons, however IPSS-R and IPSS-M are enhancements to IPSS that provide dynamic risk assessment for predicting clinical outcomes in MDS. Here, the objective was to re-classify the MDS subjects enrolled on the ASCERTAIN study by IPSS-R and IPSS-M and measure the impact of informing patient outcomes based on re-calculated risk assessment. Methods: One hundred thirty-three subjects with MDS/CMML (chronic myelomonocytic leukemia) were enrolled in ASCERTAIN and were randomly assigned either IV decitabine for cycle 1 and oral decitabine/cedazuridine for cycle 2 or the opposite treatment sequence. All subjects continuing beyond cycle 2 received oral decitabine/cedazuridine for all subsequent cycles until treatment discontinuation for disease progression, toxicity, patient's decision, or HSCT. Whole blood collected prior to treatment was used for DNA isolation and molecular abnormalities identified using next-generation sequencing (NGS) hematologic malignancy panel of 179 genes including all genes commonly mutated in MDS. In the initial analysis of clinical outcomes, subjects were classified by IPSS with response assessment by IWG 2006 IPSS low and Int-1 risk levels were categorized as lower-risk MDS (LR-MDS), whereas IPSS Int-2 and high-risk categories were categorized as higher-risk MDS (HR-MDS). Subjects with sufficient data based on (e.g., available heme parameters, cytogenetics, NGS etc.) were reclassified by IPSS-R and IPSS-M. Subjects with IPSS-R score of ≤3.5 or IPSS-M of either very low, low, or moderate low were categorized as LR-MDS. Similarly subjects with IPSS-R score of >3.5 or an IPSS-M categorization of either moderate high, high, or very high were categorized as HR-MDS. Reclassified subjects were reassessed for CR (Complete Response), OS, and LFS and Harrell's concordance index (c-index) was used to describe the level of agreement between each scale and outcomes. Results: Based on the available data, the number of MDS subjects in the different risk classifications were the following: IPSS: 117, IPSS-R: 104, and IPSS-M: 105. Thirteen and 12 subjects on the IPSS could not be reclassified in the IPSS-R and IPSS-M, respectively, including 5 Int-1 and 2 low-risk MDS cases. CMML subjects were excluded from these analyses. Re-classification generally resulted in the upgrade of the subjects from LR-MDS to HR-MDS (Fig. 1). Thirty-one (26.5%) subjects from IPSS were reallocated in the IPSS-R to different risk categories; 3 (9.7%) were downgraded and 28 (90.3%) were upgraded. Similarly on reclassification with IPSS-M 34 (32.4%) of the patients reclassified; 5 (14.8%) were downgraded and 29 (85.3%) were upgraded. For IPSS LR-MDS, 23.2% of patients achieved CR, and 22.9% in the IPSS HR-MDS. Similarly, 21.6% patients achieved CR in the IPSS-R LR-MDS, and 23.9% in the IPSS-R HR-MDS; 26.3% patients achieved CR in the IPSS-M LR-MDS, and 20.9% in the IPSS-M HR-MDS. The c-index for the IPSS was .64 (OS) and .67 (LFS), IPSS-R was .70 (OS) and .71 (LFS), and .75 (OS) and .78 (LFS) for the IPSS-M (Table1). Conclusion: Reclassification from IPSS to IPSS-R or IPSS-M upgraded multiple subjects from a LR to a HR category, describing the ASCERTAIN patient population as a majority higher risk population with worse prognosis than previously assumed based on the IPSS. The efficacy as measured by the CR rates did not change when the LR and HR categories were defined by the different risk stratification systems. In contrast, the c-index improves with migration from IPSS to IPSS-R to IPSS-M, indicating an increased discriminatory ability of IPSS-M score in comparison to IPSS and IPSS-R, to predict patient outcomes.

This paper studies the effect of different extraction procedures such as soxhlet extraction using n-hexane, distillation method and supercritical extraction (SFE) on the physicochemical properties of garlic essential oil. The yield of garlic essential oil by soxhlet extraction, steam distillation and SFE-CO2 methods was approximately 0.441, 0.124 and 0.465 %, respectively. The results of the oil analysis by gas chromatography/mass spectrometry method show the presence of five major compounds, including diallyl sulfide, diallyl disulfide, 3-vinyl-1,2-dithiacyclohex-4-ene, 3-vinyl-1,2-dithiacyclohex-5-ene and diallyl trisulfide. The antioxidant activity of the essential oil obtained by the SFE-CO2 method was significantly higher than by the distillation method, but was lower than the acid ascorbic one. Keywords Garlic essential oil, SFE, GC-MS, antioxidant activity, extraction. References [1] R. Lawrencea, K. Lawrenceb, Antioxidant activity of garlic essential oil (Allium Sativum) grown in north Indian plains, Asian Pacific Journal of Tropical Biomedicine 1 (2011) 51-54. https://doi.org/10.1016/S2221-1691(11)60122-6.[2] Dziri, H. Casabianca, B. Hanchi, K. Hosni, Composition of garlic essential oil (Allium sativum L.) as influenced by drying method, Journal of Essential Oil Research 26 (2014) 91-96. https://doi.org/10.1080/10412905.2013.868329.R.[3] Li, W. Chen, W. Wang, W. Tian, X.Z. Rrui, Extraction of essential oils from garlic (Allium sativum) using ligarine as solvent and its immunity activity in gastric cancer rat, Medicinal Chemistry Research 19 (2010) 1092-1105. https://doi.org/10.1007/s00044-009-9255-z.[4] M.K. Gafar, A.U. Itodo, A. A. Warra, L. Abdullahi, Extraction and Physicochemical Determination of Garlic (Allium sativum L) Oil, International Journal of Food and Nutrition science 1 (2012) 4-7. [5] A.P. Sa´nchez-Camargo, J.A. Mendiola, E. Iba´n˜ez, M. Herrero, Supercritical Fluid Extraction, Reference Module in Chemistry, Molecular Sciences and Chemical Engineering (2014) 1-17. https://doi.org/10.1016/b978-0-12-409547-2.10753-x.[6] A. Rafe, M. S. Nadjafi, Physicochemical characteristics of garlic (Allium sativum L.) oil: Effect of extraction procedure, International Journal of Nutrition and Food Sciences 3 (2014) 1-5. https://doi.org/10.11648/j.ijnfs.s.2014030601.11.[7] J. M. del Valle, C. Mena, M. Budinich, Extraction of garlic with supercritical CO2 and conventional organic solvents, Brazilian Journal of Chemical Engineering, 25 (2008) 535-542. https://doi.org/10.1590/S0104-66322008000300011.[8] A.E. Andreatta, G. Foco, G. Mabe, S.B. Bottini, Extraction of garlic oil with quasi-critical solvents, 4th Mercosur Congress on Process Systems Engineering (2014) 1-9.[9] H. Kamali, N. Aminimoghadamfarouj, E. Golmakani, A. Nematollahi, The optimization of essential oils supercritical CO2 extraction from Lavandula hybrida through static-dynamic steps procedure and semi-continuous technique using response surface method, Pharmacognosy Res 7 (2015) 57-65. https://doi.org/10.4103/0974-8490.147209.[10] L.D. Lawson, Z.J. Wang, B.G. Hughes, Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic products, Planta Med, 57 (1991) 363-370. https://doi.org/10.1055/s-2006-960119.[11] E. A. O'Gara, D. J. Hill, D. J. Maslin, Activities of Garlic Oil, Garlic Powder, and Their Diallyl Constituents against Helicobacter pylori, Applied and Environmental Microbiology 66 (2000) 2269-2273. https://doi.org/10.1128/aem.66.5.2269-2273.2000.[12] X. Qiao, Molecular distillation separation and purification of essential oils of garlic, Food science Shandong 5 (2007) 60.[13] M. Iranshahi, A review of volatile sulfur-containing compounds from terrestrial plants: biosynthesis, distribution and analytical methods, The Journal of Essential Oil Research, 24 (2012) 393-434. https://doi.org/10.1080/10412905.2012.692918.[14] M. Corzo-Martı´nez, N. Corzo, M. Villamiel, Biological properties of onions and garlic, Trends in Food Science & Technology 18 (2007) 609-625. https://doi.org/10.1016/j.tifs.2007.07.011.[15] K. Khoshtinat, M. Barzegar, M. A. Sahari, Z. Hamidi, Comparison of Antioxidant and Antibacterial Activities of Free and Encapsulated Garlic Oil with Beta-cyclodextrin, Applied food biotechnology 3 (2016) 254-268. https://doi.org/10.22037/afb.v3i4.12631.