Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods

Casati, S.,Aschberger, K.,Barroso, J.,Casey, W.,Delgado, I.,Kim, T. S.,Kleinstreuer, N.,Kojima, H.,Lee, J. K.,Lowit, A.,Park, H. K.,Ré,gimbald-Krnel, M. J.,Strickland, J.,Whelan, M.,Yang, Y.,Zua Springer Berlin Heidelberg 2018 Archives of toxicology Vol.92 No.2

<P>Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4–5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate adoption of defined approaches for skin sensitisation assessments.</P>

Classical and Quantum Chaos and Control of Heat Flow

Giulio Casati,C. Mejia-Monasteo 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.50 No.1I

We discuss the problem of heat conduction in classical and quantum low-dimensional systems from a microscopic point of view. At the classical level we provide convincing numerical evidence for the validity of the Fourier law of heat conduction in linear mixing systems, i.e., in systems without exponential instability. At the quantum level, where motion is characterized by the lack of exponential dynamical instability, we show that the validity of the Fourier law is in direct relation to the onset of quantum chaos. We then study the phenomenon of thermal recti.cation and brie°y discuss the dierent types of microscopic mechanisms that lead to the recti.cation of heat °ow. The control of heat conduction by nonlinearity opens the possibility to propose new devices, such as a thermal recti.er.

Design of cellular, satellite, and integrated systems for 5G and beyond

Kim, Junhyeong,Casati, Guido,Cassiau, Nicolas,Pietrabissa, Antonio,Giuseppi, Alessandro,Yan, Dong,Strinati, Emilio Calvanese,Thary, Marjorie,He, Danping,Guan, Ke,Chung, Heesang,Kim, Ilgyu Electronics and Telecommunications Research Instit 2020 ETRI Journal Vol.42 No.5

5G AgiLe and fLexible integration of SaTellite And cellulaR (5G-ALLSTAR) is a Korea-Europe (KR-EU) collaborative project for developing multi-connectivity (MC) technologies that integrate cellular and satellite networks to provide seamless, reliable, and ubiquitous broadband communication services and improve service continuity for 5G and beyond. The main scope of this project entails the prototype development of a millimeter-wave 5G New Radio (NR)-based cellular system, an investigation of the feasibility of an NR-based satellite system and its integration with cellular systems, and a study of spectrum sharing and interference management techniques for MC. This article reviews recent research activities and presents preliminary results and a plan for the proof of concept (PoC) of three representative use cases (UCs) and one joint KR-EU UC. The feasibility of each UC and superiority of the developed technologies will be validated with key performance indicators using corresponding PoC platforms. The final achievements of the project are expected to eventually contribute to the technical evolution of 5G, which will pave the road for next-generation communications.

Endophytic Bacterial Diversity in Grapevine (Vitis vinifera L.) Leaves Described by 16S rRNA Gene Sequence Analysis and Length Heterogeneity-PCR

Daniela Bulgari,Paola Casati,Lorenzo Brusetti,Fabio Quaglino,Milena Brasca,Daniele Daffonchio,Piero Attilio Bianco 한국미생물학회 2009 The journal of microbiology Vol.47 No.4

Diversity of bacterial endophytes associated with grapevine leaf tissues was analyzed by cultivation and cultivation-independent methods. In order to identify bacterial endophytes directly from metagenome, a protocol for bacteria enrichment and DNA extraction was optimized. Sequence analysis of 16S rRNA gene libraries underscored five diverse Operational Taxonomic Units (OTUs), showing best sequence matches with γ-Proteobacteria, family Enterobacteriaceae, with a dominance of the genus Pantoea. Bacteria isolation through cultivation revealed the presence of six OTUs, showing best sequence matches with Actinobacteria, genus Curtobacterium, and with Firmicutes genera Bacillus and Enterococcus. Length Heterogeneity-PCR (LH-PCR) electrophoretic peaks from single bacterial clones were used to setup a database representing the bacterial endophytes identified in association with grapevine tissues. Analysis of healthy and phytoplasma- infected grapevine plants showed that LH-PCR could be a useful complementary tool for examining the diversity of bacterial endophytes especially for diversity survey on a large number of samples.

Comparison of Parecoxib and Proparacetamol in Endoscopic Nasal Surgery Patients

Yigal Leykin,Andrea Casati,Alessandro Rapotec,Massimiliano Dalsasso,Luigi Barzan,Guido Fanelli,Tommaso Pellis 연세대학교의과대학 2008 Yonsei medical journal Vol.49 No.3

Purpose: The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. Materials and Methods: Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (IV) administration of either 40mg of parecoxib (n=25) or 2g of proparacetamol (n=25) 15 min before discontinuation of total IV anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. Results: The area under the curve of VAS (AUCVAS) calculated during the study period was 669 (28-1901) cm‧min in the proparacetamol group and 635 (26-1413) cm‧min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p≥0.05), while mean morphine consumption was 5-3.5mg and 5-2.0mg in the proparacetamol groups and parecoxib, respectively (p≥0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24h after surgery. Conclusion: In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.

International regulatory requirements for skin sensitization testing

Daniel, Amber B.,Strickland, Judy,Allen, David,Casati, Silvia,Zuang, Valé,rie,Barroso, Joã,o,Whelan, Maurice,Ré,gimbald-Krnel, M.J.,Kojima, Hajime,Nishikawa, Akiyoshi,Park, Hye-Kyung Elsevier 2018 Regulatory toxicology and pharmacology Vol.95 No.-

<P><B>Abstract</B></P> <P>Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We reviewed regulatory requirements for skin sensitization testing, by chemical sector, of seven countries or regions. </LI> <LI> This review summarizes data needs for hazard classification, potency classification, and risk assessment. </LI> <LI> We identify preferred test methods and note whether non-animal alternative test methods are acceptable. </LI> <LI> This effort will inform an international strategy for implementing non-animal approaches for skin sensitization assessment. </LI> </UL> </P>

SbTT8, a New Sorghum bHLH Transcription Factor that Rescues Brown Seed Coat Phenotype in Arabidopsis tt8 Mutant Plants

Salez M. Agustina,González Javier M.,Bernacchini Joana C.,Rodriguez M. Victoria,Ferreyra M. Lorena Falcone,Casati Paula,Rius Sebastián P. 한국식물학회 2022 Journal of Plant Biology Vol.65 No.6

Flavonoids are polyphenolic compounds and color most flowers, fruits and seeds. The regulation of flavonoid biosynthetic genes is directed by ternary complexes composed of MYB-bHLH-WD40 transcription factors. DNA-binding bHLH proteins are widely distributed in higher plants and comprise the second largest transcription factor family. The regulation of flavonoid synthesis by bHLH has been extensively studied in vascular plants, most functionally characterized in Arabidopsis. Sorghum is one of the most economically important crops worldwide. Despite 169 bHLH genes were identified in this cereal, few studies have reported their roles in seed coat pigmentation. Here we identified and characterized SbTT8, a sorghum bHLH-domain protein, through molecular modeling and complementation studies in Arabidopsis tt8 mutant. SbTT8 partially rescues the brown seed color and dormancy in Arabidopsis tt8 mutants. We show that SbTT8 is significantly larger than AtTT8 and holds a Lys467 residue where AtTT8 has an Ala367, within the DNA-recognition motif conserved throughout the bHLH family. This change likely affects how SbTT8 interacts with the target DNA, as compared with AtTT8. Our results shed light on the different phenotypes witnessed for A. thaliana transgenic lines expressing SbTT8 from sorghum, as well as the regulation of genes encoding enzymes for flavonoid biosynthesis.