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Results for “Extended Dynamic Range”

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At least 19 recordsLinked to original sources

PubMed2026

Reframing Proteomics Measurement: Super Mass Spectrometry Framework and the Role of Delayed Electrospray Ionization Technique.

Dynamic range, repeatability, and reproducibility remain the central limitations of data-independent acquisition (DIA) proteomics. Current workflows emphasize protein group identification counts and throughput, but these metrics mask the fundamental measurement challenge: generating a repeatable, reproducible, high-fidelity, and relatively complete digital representation of complex proteomes. In particular, plasma proteomics spans more than 10 orders of magnitude in protein abundance, far exceeding the capacity and dynamic range of any single mass spectrometer. Incremental advances have not closed this gap. In this Perspectives article, I introduce the Super Mass Spectrometry framework and then highlight the Delayed Electrospray Ionization (Delayed-ESI) technique, as a practical approach to address these limitations. By producing compositionally identical but temporally staggered ion beams, the Delayed-ESI technique enables deterministic remeasurement of the same analyte profile, supporting various novel strategies to improve analytical figures of merit. While recent implementations of the Delayed-ESI technique have emphasized throughput, I argue that the broader value of the Delayed-ESI technique lies in extending dynamic range and improving repeatability and reproducibility─objectives that should take precedence if proteomics is to evolve into a robust measurement science capable of supporting population-scale proteomics studies.

Proteomics↗

PubMed1977

Lipoxygenic micromethod for specific determination of lipase activity in serum and duodenal fluid.

We propose a rapid enzymatic micromethod for the specific determination of lipase (EC 3.1.1.3) activity in serum and duodenal fluid. Free linoleic acid produced during 10-min incubation of 10 mul of sample with 1 ml of substrate (trillinolein emulsion) at 30 degrees C is converted by lipoxygenase (EC 1.99.2.1), in a coupled reaction, to its hydroperoxide, which is measured photometrically after solubilizing the reaction mixture in ethanol. Lipase activity is calculated from the rate of hydroperoxide formation, with linoleic acid as primary standard. The velocity of the reaction is greatest at pH 8.8, 35-37 degrees C, and a deoxycholate concentration of 3.6 mmol/liter. The energy of activation is 6.7 kcal/mol. The differing "apparent" Km values obtained for lipase in undiluted serum (4 X 10(-5) mol/liter) and in albumin-based diluents (1 X 10(-5) mol/liter) indicate the presence of a competitive inhibitor in the serum matrix. We detected no lipase activity in urine. Results by the proposed method correlate well with those by a copper soap extraction method (r = 0.95), but values are significantly higher for pancreatitis patients' sera (slope 1.6). The linear dynamic range extends to 1000 U/liter. Hemolysis, lipemia, and hyperbilirubinemia do not interfere. The normal range is 40-60 U/liter. Lipase activity of pancreatitis patients generally exceed 1000 U/liter during the acute phase and 250 U/liter for as long as 10 days after it.

Amylases↗

PubMed1978

Principles and applications of a dynamically focused phased array real time ultrasound system.

The physical principles and clinical applications of a high-resolution, dynamically focused phased-array real time ultrasound are described. Advantages of the real time technique include rapid survey capability, efficient selection of an appropriate tomographic plane, identification of pulsating structures, and dynamic studies. The capabilities of a high resolution phased array with extended dynamic focusing to a range of 15-20 cm are demonstrated in vascular, abdominal, and obstetric imaging. Appropriate clinical examples showing normal and pathological anatomy are presented. Comparisons with conventional B scans are illustrated.

Abdomen↗

PubMedDate not supplied

[Recording of ventricular pressure by conventional catheter manometer systems. Efficiency of several combinations of conventional catheters, modern transducers and catheter-flush systems (author's transl)].

The experimentally in vitro determined dynamic response characteristics of 38 catheter manometer systems were uniform in the worst case to 5 c.p.s. and optimally to 26 c.p.s. Accordingly, some systems are only satisfactory for ordinary pressure recording in cardiac rest, while better systems record dp/dt correct up to moderate inotropic stimulation of the heart. In the frequency range of uniform response (amplitude error less +/- 5%) the phase distortion is also negligible. In clinical application the investigator is often restricted to special type of cardiac catheter. In this case a low compliant transducer yields superior results. In all examined systems the combination with MSD 10 transducers is best, whereas the combination with P 23 Db transducers leads to minimal results. An inadequate system for recording ventricular pressure pulses leads in most cases to overestimations of dp/dtmax. The use of low frequency pass filters to attenuate higher frequency artefacts is, under clinical conditions, not suitable for extending the range of uniform frequency response. The dynamic response of 14 catheter manometer systems with two types of continuous self flush units was determined. The use of the P 37 flush unit in combination with small internal diameter catheters leads to serious error in ordinary pressure recording, due to amplitude distortion of the lower harmonics. The frequency response characteristics of the combination of an Intraflow flush system and MSD 10 transducer was similar to the non-flushing P 23 Db transducer feature.

Blood Pressure Determination↗

PubMed2026

Monitoring kinetic changes and restriction of influenza A virus RNA species during infection using a Flu-Stranded CRISPR platform.

UNLABELLED: Influenza A virus (IAV) generates three closely related RNA species: viral RNA (vRNA), complementary RNA (cRNA), and messenger RNA (mRNA), whose strand-specific quantification remains limited by sensitivity and quantitative dynamic range, particularly at low RNA abundance. Here, we developed Flu-Stranded CRISPR-Cas12a, a strand-specific detection platform integrating tagged reverse transcription, segment-specific PCR, and Cas12a collateral cleavage to support quantitative analysis of all three RNA species across a broad dynamic range. The assay enables reliable detection down to 102 copies per reaction, extending the lower quantitative boundary relative to both SYBR Green and TaqMan reverse transcription quantitative PCR (RT-qPCR) under matched conditions. Validated in infected cell lines, murine lung tissues, and clinical nasopharyngeal specimens, the platform enabled subtype-discriminating, strand-resolved detection, including samples near or below the quantitative range of SYBR Green RT-qPCR. Using finely resolved infection time-course analyses in NP and NA segments, we identified a reproducible early vRNA decline within the early post-infection phase. This decline was partially attenuated in RIG-I knockout A549 cells, while subsequent vRNA accumulation was enhanced, consistent with a modulatory rather than essential role for RIG-I in early viral RNA dynamics. Subcellular fractionation localized this decline to cytoplasmic incoming genomes. In contrast, importazole-mediated inhibition of nuclear import abolished vRNA recovery without affecting the early decline, indicating that nuclear entry functionally separates early genome reduction from subsequent productive replication. These findings establish Flu-Stranded CRISPR-Cas12a as a strand-resolved framework for monitoring IAV RNA dynamics and reveal an early window of genome vulnerability during cytoplasmic transit that shapes infection outcome. IMPORTANCE: The early fate of incoming influenza virus genomes remains unclear, limiting our understanding of how infection is established or aborted in host cells. We developed Flu-Stranded CRISPR-Cas12a, a strand-specific platform for sensitive and quantitative analysis of influenza viral RNA (vRNA), complementary RNA (cRNA), and messenger RNA (mRNA) across experimental and clinical samples. Using high-resolution time-course analysis, we identified a reproducible early decline in vRNA during the post-entry phase. Our data suggest that this early genome loss arises from multiple processes, with RIG-I acting as a modulatory factor rather than a primary driver. Subcellular fractionation localized this effect to cytoplasmic incoming genomes, whereas importin-β-mediated nuclear entry was required for subsequent vRNA recovery. These findings support a model of an early cytoplasmic phase of genome attrition that is distinct from replication and provide a framework for understanding early influenza RNA kinetics and for guiding strand-resolved diagnostics and antiviral evaluation.

CRISPR-Cas12a↗

PubMed1976

Psychopathometry and homogenous syndrome dynamics.

The principle of homogeneous dynamic of syndromes means that diminishing of single psychic functions or the severeness of syndromes is correlated to the total syndrome. The validity of this principle was alleged for reversible physically founded psychoses and for cyclothymic depressions. Various empirical investigations confirm the validity of the principle of homogeneous dynamic of syndromes. These findings suggest practical benefit for the development of psychopathometric procedures: constructions of short tests. Perhaps the range of validity of the principle of homogeneous dynamic of syndromes may be extended on cyclothymic mania, too. Empirical investigations will prove this question.

Cyclothymic Disorder↗

PubMed1975

A sex-chromosome hybrid zone in the grasshopper Podisma pedestris (Orthoptera: Acrididae).

Podisma pedestris exists as both an XO and neoXY form in the Southern French Alps. These chromosome types are shown to be contiguously allopatric and hybrid populations have been located in several places. Hybridisation appears to be occurring freely, but the hybrid zones are quite narrow. In several places the two distributions are separated by geographic barriers such as high mountain ridges and lowlands. The history of this XY chromosomal race is discussed in the light of the genetic dynamics of hybrid zones and the biogeography of this situation. Its origin is probably post-glacial, and it may be extending its range as a salient in one region. A comparison of the porperties of similar cases indicates that the formation of such chromosomal races may be a frequent event in relatively immobile species that are subjected to isolation and expansion by major climatic and ecological changes.

France↗

PubMed1979

A model describing nonlinearities in hearing by active processes with saturation at 40 dB.

Data from literature related to nonlinearities of the peripheral part of the hearing system are collected and extended by results from measurements of acoustical responses, masking, cubic difference tones and Zwicker tones. The data indicate 40 dB as a significant value for the dynamic range in neurophysiology as well as for the sensation level in psychoacoustics dividing the total level range into two areas of different characteristics. A preliminary model assuming that the outer hair cells act as an amplifier which contains saturation (corresponding to 40 dB) and feed back to sensitize the inner hair cells is used to describe the measured effects at least qualitatively.

Auditory Fatigue↗

PubMed1975

White noise analysis of Phycomyces light growth response system. II. Extended intensity ranges.

By means of white gaussian noise stimulation, the Wiener kernels are derived for the Phycomyces light growth response for a variety of intensity conditions. In one experiment the intensity I, rather than log I, is used as the input variable. Under the very limited dynamic range of that experiment, the response is fairly linear. To examine the dependence of the kernels on dynamic range, a series of experiments were performed in which the range of log I was halved and doubled relative to normal. The amplitude of the kernels, but not the time course, is affected strongly by the choice of dynamic range, and the dependence reveals large-scale nonlinearities not evident in the kernels themselves. In addition kernels are evaluated for experiments at a number of absolute intensity levels ranging from 10(-12) to 10(-3) W/cm2. The kernel amplitudes are maximal at about 10(-6) W/cm2. At 10(-12) W/cm2, just above the absolute threshold, the respond is very small. The falloff at high intensity, attributable to inactivation of the photoreceptor, is analyzed in the framework of a first-order pigment kinetics model, yielding estimates for the partial extinction coefficient for inactivation epsilonI455 = (1.5 +/- 0.2) X 10(4) liter/mol-cm and a regeneration time constant of tau = (2.7 +/- 0.6) min. A model is introduced which associates the processes of adaptation and photoreceptor inactivation. The model predicts that the time constants for adaptation and pigment should be identical. This prediction is consistent with values in this and the preceding paper. The effects of pigment inactivation are simulated by a linear electronic analog circuit element, which may be cascaded with the linear simulator circuit in the preceding paper.

Adaptation, Physiological↗

PubMedDate not supplied

Psychophysical evaluation of cochlear prostheses in a monkey model.

Functional aspects of cochlear prostheses implanted in the scala tympani were tested in monkeys trained to perform a simple reaction-time task. Thresholds for detection of electrical stimulation and dynamic ranges were tested for a wide range of frequencies of sinusoidal stimulation and for biphasic rectangular pulses of various durations and repetition rates. The results are comparable with available data from implanted human patients and extend these findings, exploring various aspects of electrical stimulation in greater detail.

Acoustic Stimulation↗

PubMed2004

EnsMart: a generic system for fast and flexible access to biological data.

The EnsMart system (www.ensembl.org/EnsMart) provides a generic data warehousing solution for fast and flexible querying of large biological data sets and integration with third-party data and tools. The system consists of a query-optimized database and interactive, user-friendly interfaces. EnsMart has been applied to Ensembl, where it extends its genomic browser capabilities, facilitating rapid retrieval of customized data sets. A wide variety of complex queries, on various types of annotations, for numerous species are supported. These can be applied to many research problems, ranging from SNP selection for candidate gene screening, through cross-species evolutionary comparisons, to microarray annotation. Users can group and refine biological data according to many criteria, including cross-species analyses, disease links, sequence variations, and expression patterns. Both tabulated list data and biological sequence output can be generated dynamically, in HTML, text, Microsoft Excel, and compressed formats. A wide range of sequence types, such as cDNA, peptides, coding regions, UTRs, and exons, with additional upstream and downstream regions, can be retrieved. The EnsMart database can be accessed via a public Web site, or through a Java application suite. Both implementations and the database are freely available for local installation, and can be extended or adapted to 'non-Ensembl' data sets.

Animals↗

PubMed2026

Ribosome dynamics at the conserved PGP motif governs 2A peptide-bond-skipping efficiency.

Viral 2A oligopeptides drive an unusual ribosome recoding event in which peptide-bond formation fails at a conserved PG↓P motif, producing two discrete proteins without canonical termination. Despite decades of study, the molecular basis of 2A-mediated peptide-bond skipping remains poorly understood. Here, we combine quantitative 2A reporters with high-resolution ribosome profiling to interrogate ribosome dynamics at the core 2A sequences. We identify a pausing event at the terminal proline codon of the PGP motif that functions as a kinetic decision point: ribosome dwell time at this site inversely correlates with skipping efficiency. Increasing nascent chain flexibility by inserting linkers immediately upstream of the 2A sequence reduces ribosome occupancy at the terminal proline codon and enhances peptide-bond skipping. Strikingly, amino acid repeats positioned distally upstream also modulate 2A activity, indicating long-range coupling between nascent chain properties outside of the ribosome and the peptidyl transferase center inside the ribosome. In particular, hydrophobic residues potently suppress skipping, an effect that can be rescued by extending flexible segments within the peptide exit tunnel. Together, our findings support a model in which nascent chain features-beyond the core 2A motif-dynamically tune ribosomal recoding efficiency through co-translational feedback into the catalytic center.

Ribosomes↗

PubMed1979

Studies on protein folding, unfolding and fluctuations by computer simulation. III. Effect of short-range interactions.

The theoretical model of proteins on the two-dimensional square lattice, introduced previously, is extended to include the specific short-range interactions. Attractive long-range interactions with various specificities and non-specific repulsive long-range interactions in the form of self-avoidance of the polymer chain are also operative in the model. Dynamics of the model protein is studied by a Monte Carlo method. The short-range interactions are found to accelerate the folding and unfolding transitions. Non-specific part of the attractive long-range interactions have a competing effect of decelerating the transitions. When the short-range interactions are weighted beyond a certain extent over the attractive long-range interactions are weighted beyond a certain extent over the attractive long-range interactions, the all-or-none character of the folding and unfolding transitions is destroyed. How the destruction proceeds is quantitatively expressed in terms of the S-H curves. The limiting case of dominance of the specific short-range interactions over the attractive long-range interactions is studied in detail. The lattice polymer in this limit does not behave like a globular protein at all. This observation leads to a reexamination of the currently popular notion of the dominance of the short-range interactions. A new concept of consistency is proposed to replace it. Possible mechanisms of the acceleration of the transitions by the specific short-range interactions are discussed.

Computers↗

PubMed2025

A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation.

The Klebsiella pneumoniae species complex inhabits a wide variety of hosts and environments, and is a major cause of antimicrobial resistant infections. Genomics has revealed the population comprises multiple species/sub-species and hundreds of distinct co-circulating sub-lineage (SLs) that are associated with distinct gene complements. A substantial fraction of the pan-genome is predicted to be involved in metabolic functions and hence these data are consistent with metabolic differentiation at the SL level. However, this has so far remained unsubstantiated because in the past it was not possible to explore metabolic variation at scale. Here, we used a combination of comparative genomics and high-throughput genome-scale metabolic modeling to systematically explore metabolic diversity across the K. pneumoniae species complex (n = 7,835 genomes). We simulated growth outcomes for each isolate using carbon, nitrogen, phosphorus, and sulfur sources under aerobic and anaerobic conditions (n = 1,278 conditions per isolate). We showed that the distributions of metabolic genes and growth capabilities are structured in the population, and confirmed that SLs exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between SLs, effectively extending the range of conditions supporting individual growth. We propose that these substrate specializations may promote the existence and persistence of co-circulating SLs by reducing nutrient competition and facilitating commensal interactions. Our findings have implications for understanding the eco-evolutionary dynamics of K. pneumoniae and for the design of novel strategies to prevent opportunistic infections caused by this World Health Organization priority antimicrobial resistant pathogen.

Klebsiella pneumoniae↗

PubMed1977

Pulmonary mechanics in normal rats.

A versatile, whole-body pressure, or volume plethysmographic system for the study of pulmonary mechanics in anesthetized, tracheotomized rats has been described. Lung volumes and lung compliance values were in good agreement with those previously reported. Pulmonary resistance and chest wall compliance values were lower than those previously reported. Total dynamic compliance remained independent of respiratory frequency between 40 and 320 breaths/min. Flow-limiting behavior was demonstrated from a series of imposed forced expiratory maneuvers of graded effort. With a deflation pressure of 30 cmH2O, the effort-independent range of maximum flow extended to 40-50% of vital capacity. Maximal flow-static recoil pressure relationships were essentially linear over the effort independent portion of the flow-volume curve. Substitution of a low-density gas mixture (80% He-20% O2) for air resulted in increased forced expiratory flow rates but the magnitude of the response was considerably less than that which has been reported in man.

Airway Resistance↗

PubMed2026

Engineering the Vero Cell Lineage: Toward a Programmable Vaccine Manufacturing Platform.

Vero cells remain an indispensable continuous substrate for human viral vaccine manufacturing. Despite decades of empirical process optimization, intrinsic genomic instability, including segmental aneuploidy and dynamic chromatin rearrangements, continues to limit the durability of engineered phenotypes under sustained viral burden and bioreactor stress. Here, we review the expanding engineering toolkit for the Vero lineage across a three-layered functional framework: the membrane interface, cytoplasmic foundry, and nuclear blueprint, evaluating translational prospects at each level. Receptor transplantation and morphological reprogramming have broadened viral entry range and enabled suspension-adapted culture formats, while metabolic flux management and temporally controlled apoptosis modulation have addressed intracellular production bottlenecks, albeit often with trade-offs between productivity, biosafety, and long-term population stability. At the genomic level, targeted perturbations of transcriptional regulators and emerging epigenetic interventions offer more durable gains, yet expression drift, clonal heterogeneity, and karyotypic instability during extended passaging highlight the need for locus-level precision rather than constitutive trait installation. Looking forward, infection-responsive dynamic logic circuits and the systematic identification of Vero-specific genomic safe harbors could shift the paradigm toward a conditionally responsive manufacturing architecture. Collectively, these advances suggest a pathway for transitioning the Vero lineage from a passive, empirically optimized biological substrate into a conditionally responsive, genomically stable, and programmable platform for modern vaccine preparedness.

Vero cells↗

PubMedDate not supplied

Controlled deposition of tantalum powder in a cast of the human airways: applications for aerosol bronchography.

A hollow latex cast of the human larynx and tracheobronchial tree extending to 2 mm diameter airways "inhaled" tantalum powder (mass median aero-dynamic diameter equals 9.2 mum, omicron-g equals 1.41) at 8 liters/min. Tantalum deposited within the cast as predicted by preliminary deposition calculations. These calculations predicted deposition surface densities among greater than 2 mm diam. airways to have a range of similar to 2:1, and also predicted less than 5% alveolar deposition. A deposition surface density of 8 mg/cm-2 provided good bronchographic visualization. Single rice grains located within some airways were distinctly outlined. The small amount of tantalum needed to outline the airways be a simulated voluntary inhalation indicates that tantalum may be suitable for use as a bronchographic contrast medium when administered under strictly controlled exposure conditions.

Aerosols↗

PubMed2026

Integrative multi-omics and single-cell analysis identifies EGFR pathway activation and metabolic reprogramming as potential synthetic lethal vulnerabilities in resistance to the FGFR inhibitor AZD4547.

BACKGROUND: Although fibroblast growth factor receptor (FGFR) inhibitors (FGFRi) have demonstrated clinical promise, the inevitable emergence of acquired resistance remains a critical bottleneck, severely compromising their long-term clinical efficacy. The pan-cancer molecular landscape and heterogeneous mechanisms driving this resistance, ranging from genetic alterations to dynamic network rewiring, remain poorly understood. METHODS: We integrated large-scale pharmacogenomic profiling of the FGFR inhibitor AZD4547 from the GDSC2 and PRISM databases with single-cell RNA sequencing to dissect the multi-omics landscape of FGFRi resistance across 312 cell lines from 8 cancer types. This multi-omics framework was further extended by machine learning modeling and systematic synthetic lethality screening to uncover actionable therapeutic targets. In vitro viability assays and western blot analysis were subsequently conducted to experimentally evaluate the predicted FGFR-EGFR synthetic lethality. RESULTS: Our dual-database analysis unveiled a multi-dimensional atlas of FGFRi resistance. We identified cancer-specific genomic drivers, such as ELF4 amplification in glioblastoma, alongside key transcriptomic markers including UCP2 and FSCN1, highlighting a shift towards metabolic reprogramming and epithelial-mesenchymal transition (EMT). Single-cell analysis unveiled that resistance is linked to the heterogeneous enrichment of baseline subpopulations characterized by distinct metaprograms, including cell-cycle dysregulation. Furthermore, a random forest model built on a LASSO-derived transcriptomic signature was constructed, demonstrating promising predictive capability for AZD4547 sensitivity (mean test-set AUC = 0.73, 95% CI [0.63, 0.80]); the signature generalized well to erdafitinib but showed limited transferability to some other FGFR inhibitors (e.g. pemigatinib, BGJ398). Most notably, our synthetic lethal screening revealed a convergent reliance on compensatory RTK signaling (specifically EGFR pathway enrichment) and downstream MAPK/PI3K cascades in resistant phenotypes, providing converging computational evidence for EGFR pathway activation as an adaptive bypass mechanism. This predicted synthetic lethality was experimentally supported in two FGFR-dependent cell line models (RT112 and CCLP1), in which combined FGFR-EGFR inhibition produced marked synergistic antiproliferative effects. CONCLUSIONS: This study establishes a comprehensive multi-omics atlas of resistance to the FGFR inhibitor AZD4547, delineating convergent mechanisms of metabolic reprogramming and EGFR-mediated bypass signaling. Our findings characterize the resistance as a dynamic network rewiring and nominate rational combination strategies to overcome this therapeutic bottleneck. While FGFR-EGFR co-inhibition is experimentally supported, metabolic co-targeting remains a computationally derived, hypothesis-generating strategy.

Benzamides↗