Adopting SFC Technology into the Purification Process

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This business case examines the benefits of deploying SFC Technology at Dart NeuroScience LLC. The benefits include solvent use and waste by more than a third, a tenfold reduction in evaporation time, and sample processing time was cut by a third compared to high performance liquid chromatography (HPLC).

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Adopting SFC Technology into the Purification Process

This presentation describes the benefits of a hardware and software platform that dramatically advances LC and LC-MS method development by applying Analytical Quality by Design (AQbD) approaches in a 100% regulatory compliance supported framework. This AQbD aligned platform includes Waters Empower™ Chromatography Data System Software with enhanced Fusion QbD® Software, the Waters® ACQUITY UPLC H-Class PLUS, a PDA detector, and QDa Mass Detector. New software capabilities that optimize and simplify the use of mass detection in the AQbD method development workflow have been added. Visit methods.waters.com for more information

Webinar - Pharmacopeial Modernization: How Will Your Chromatography Workflow ...

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In this webinar, Dr. Leonel Santos and Dr. Horacio Pappa from the United States Pharmacopeia (USP) will provide an overview of its pharmacopeial harmonization and modernization efforts. The pair will also review changes described in the pending USP General Chapter <621> on liquid chromatography (LC), which will provide increased flexibility for gradient methods. Amanda Dlugasch, from Waters Corporation, will follow with an illuminating case study, which leverages USP <621> allowable adjustments to illustrate the benefits of modernizing methods, including migrating HPLC methods to UHPLC or UPLC, without the need to revalidate. Topics covered in this webinar will include: - Pharmacopeial monograph modernization prioritization scheme - Review of USP General Chapter <621> current allowable adjustments to validated chromatographic methods and forthcoming updates - Case study on the migration of isocratic and gradient pharmacopeial methods to modern chromatography column technology, highlighting improved method performance and throughput Replay the webinar, hosted by SelectScience: https://www.selectscience.net/webinars/pharmacopeial-modernization-how-will-your-chromatography-workflow-benefit/?webinarID=1228

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extra-chromosomal-inheritance[1].pptx.pdfpdf

DiyaBiswas10

Slide 1: Title Slide Extrachromosomal Inheritance Slide 2: Introduction to Extrachromosomal Inheritance Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus. Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids. Slide 3: Mitochondrial Inheritance Mitochondria: Organelles responsible for energy production. Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria. Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring. Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy. Slide 4: Chloroplast Inheritance Chloroplasts: Organelles responsible for photosynthesis in plants. Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts. Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species. Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA. Slide 5: Plasmid Inheritance Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes. Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation. Significance: Important in biotechnology for gene cloning and genetic engineering. Slide 6: Mechanisms of Extrachromosomal Inheritance Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance. Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells. Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression. Slide 7: Examples of Extrachromosomal Inheritance Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells. Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration. Slide 8: Importance of Extrachromosomal Inheritance Evolution: Provides insight into the evolution of eukaryotic cells. Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases. Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification. Slide 9: Recent Research and Advances Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA. Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases. Slide 10: Conclusion Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology. Future Directions: Continued research and technological advancements hold promise for new treatments and applications. Slide 11: Questions and Discussion Invite Audience: Open the floor for any questions or further discussion on the topic.

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We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and 30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1 . Our search finds no candidates at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to infer the properties of the evolving luminosity function without binning in redshift or luminosity that marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results, and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5 from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical models for evolution of the dark matter halo mass function.

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Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...

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Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.

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A brief information about the SCOP protein database used in bioinformatics. The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.

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Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.

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RNA INTERFERENCE: UNRAVELING GENETIC SILENCING

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Introduction: RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression. It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences. dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants. This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes. What are small ncRNAs? micro RNA (miRNA) short interfering RNA (siRNA) Properties of small non-coding RNA: Involved in silencing mRNA transcripts. Called “small” because they are usually only about 21-24 nucleotides long. Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered). Silence an mRNA by base pairing with some sequence on the mRNA. Discovery of siRNA? The first small RNA: In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the development of the worm C. elegans. Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14. Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions. Types of RNAi ( non coding RNA) MiRNA Length (23-25 nt) Trans acting Binds with target MRNA in mismatch Translation inhibition Si RNA Length 21 nt. Cis acting Bind with target Mrna in perfect complementary sequence Piwi-RNA Length ; 25 to 36 nt. Expressed in Germ Cells Regulates trnasposomes activity MECHANISM OF RNAI: First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces. Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands. The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it. THE RISC COMPLEX: RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA Unwinding of double stranded Si RNA by ATP independent Helicase Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA. DICER: endonuclease (RNase Family III) Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC) One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute ARGONAUTE PROTEIN : 1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA 2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity. MiRNA: The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .

(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...

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Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes. In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.

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Since volcanic activity was first discovered on Io from Voyager images in 1979, changes on Io’s surface have been monitored from both spacecraft and ground-based telescopes. Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images show that a plume deposit from a powerful eruption at Pillan Patera has covered part of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive optics at visible wavelengths.

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