scholarly journals Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor

2015 ◽  
Vol 14 ◽  
pp. CIN.S35374 ◽  
Author(s):  
Hermann B. Frieboes ◽  
Louis T. Curtis ◽  
Min Wu ◽  
Kian Kani ◽  
Parag Mallick
Keyword(s):  
Cancer Detection ◽  
Protein Production ◽  
Experimental Approach ◽  
Tumor Tissue ◽  
Circulating Biomarkers ◽  
Biophysical Processes ◽  
Protein Shedding ◽  
Significant Interest ◽  
Kinetics Of ◽  
Treatment Personalization

Circulating biomarkers are of significant interest for cancer detection and treatment personalization. However, the biophysical processes that determine how proteins are shed from cancer cells or their microenvironment, diffuse through tissue, enter blood vasculature, and persist in circulation remain poorly understood. Since approaches primarily focused on experimental evaluation are incapable of measuring the shedding and persistence for every possible marker candidate, we propose an interdisciplinary computational/experimental approach that includes computational modeling of tumor tissue heterogeneity. The model implements protein production, transport, and shedding based on tumor vascularization, cell proliferation, hypoxia, and necrosis, thus quantitatively relating the tumor and circulating proteomes. The results highlight the dynamics of shedding as a function of protein diffusivity and production. Linking the simulated tumor parameters to clinical tumor and vascularization measurements could potentially enable this approach to reveal the tumor-specific conditions based on the protein detected in circulation and thus help to more accurately manage cancer diagnosis and treatment.

Sulphate metabolism in the exocrine pancreas. II. The production of sulphated macromolecules by the mouse exocrine pancreas

1978 ◽  
Vol 31 (1) ◽  
pp. 199-211
Author(s):  
N.B. Berg
Keyword(s):  
Exocrine Pancreas ◽  
Protein Production ◽  
Pancreatic Tissue ◽  
Radioactive Material ◽  
Secretory Proteins ◽  
Tissue Slices ◽  
Inorganic Sulphate ◽  
Kinetics Of ◽  
Similar Decrease

The types of sulphated macromolecules produced by the exocrine pancrease were investigated. To determine whether this tissue utilized inorganic sulphate for protein production, the in-vitro behaviour of material labelled with 35S-sulphate was compared with material labelled with [3H]leucine (secretory proteins). While incubating tissue slices in the presence of cycloheximide resulted in an immediate and nearly complete inhibition of protein synthesis, a similar decrease in production of sulphated material was not observed until after 2 h of incubation in the presence of the drug. Likewise, the kinetics of pilocarpine-induced discharge of radioactive material from pancreatic slices pulse-labelled with either 3H-Leu. or 35S-sulphate was compared. During the first 90 min of stimulation sulphated macromolecules were detected in chase medium 10–15 min prior to the appearance of 3H-labelled secretory proteins. That in-vitro behaviour of sulphated material differed from radioleucine-labelled material is indicative of the fact that the pancreas utilizes inorganic sulphate for the production of macromolecules other than secretory proteins. Lipid and proteoglycan fractions were prepared from pancreatic tissue 4 h after intraperitoneal injection of radiosulphate. The recovery of a significant amount of radioactivity in both fractions deomonstrated the ability of the pancreas to use inorganic sulphate for the production of both sulphated lipids and sulphated proteoglycans. The possible function of sulphated macromolecules in pancreatic secretion is discussed.

scholarly journals Importance of rheology in the prediction of structural transition phenomena in geopolymer matrices loaded with phosphogypsum

2019 ◽  
Vol 286 ◽  
pp. 07005
Author(s):  
N. Lahlou ◽  
M. Ouazzani Touhami ◽  
R. Hattaf ◽  
R. Moussa
Keyword(s):  
Rheological Behavior ◽  
Structural Transition ◽  
Experimental Approach ◽  
Fresh State ◽  
Hardened State ◽  
Definition Of ◽  
The Impact ◽  
Kinetics Of

Through a purely experimental approach, we proceed here to the description of the rheological behavior of the geopolymer matrices in the fresh state according to one or other of the parameters characterizing their formulation. This consolidates the different physicochemical techniques usually used for their characterization. This comes to allow us especially the definition of drafts for the implementation of empirical laws ensuring a better follow-up in the elaboration of these materials or even more optimization in their formulation. This description also allows us to follow the structural transition phenomena from the fresh state to the hardened state. We are particularly interested in demonstrating the impact of the addition of Phosphogypsum on the rheological behavior of geopolymers or on their kinetics of setting.

Preliminary study on the kinetics of oxytetracycline in shellfish exposed to an effluent of a land-based fish farm: Experimental approach

1995 ◽  
Vol 40 (2) ◽  
pp. 171-180 ◽  
Author(s):  
Hervé Le Bris ◽  
Hervé Pouliquen ◽  
Jean-Marc Debernardi ◽  
Vincent Buchet ◽  
Louis Pinault
Keyword(s):  
Experimental Approach ◽  
Fish Farm ◽  
Preliminary Study ◽  
Kinetics Of

Performance of a high-intensity 508-gene circulating-tumor DNA (ctDNA) assay in patients with metastatic breast, lung, and prostate cancer.

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA11516-LBA11516 ◽  
Author(s):  
Pedram Razavi ◽  
Bob T. Li ◽  
Wassim Abida ◽  
Alex Aravanis ◽  
Byoungsok Jung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Detection ◽  
High Intensity ◽  
Tumor Tissue ◽  
De Novo ◽  
Early Cancer ◽  
Metastatic Breast ◽  
Early Cancer Detection ◽  
Driver Mutations ◽  
Castration Resistant Prostate Cancer

LBA11516 Background: ctDNA assays can noninvasively assess tumor burden and biology by identifying tumor-derived somatic alterations. For broad applicability, including early cancer detection, an unprecedented high-intensity approach (ultra-deep sequencing of plasma cell-free DNA (cfDNA) with broad genomic coverage) is needed to address intra-patient and population-level heterogeneity. We present initial results with this approach in patients (pts) with metastatic breast (BC), non-small cell lung (NSCLC), and castration-resistant prostate cancer (CRPC). Methods: Blood and tissue were prospectively collected w/in 6 wks with no intervening therapy change from pts with de novo or progressive cancer. cfDNA and white blood cell (WBC) genomic DNA from each pt were sequenced with a 508-gene panel (2 Mb; >60,000X raw depth). cfDNA variant calling used molecular barcoding for error correction and filtering for WBC variants. Tissue was sequenced using the MSK-IMPACT assay (410 genes, 1.4 Mb, >500X depth) blinded to plasma/WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in BC and NSCLC. Results: Of 161 eligible pts, 124 (39 BC, 41 NSCLC, and 44 CRPC) were evaluable for concordance. In tissue, 864 variants were detected across the 3 tumor types, with 627 (73%) also detected in plasma: single nucleotide variants/indels - 75%, fusions - 67%, and copy number alterations - 58%. In 90% of pts, at least 1 of the variants detected in tumor tissue was also detected in plasma: BC - 97%, NSCLC - 85%, CRPC - 84%. Most actionable mutations detected in tissue were also detected in plasma (54/71, 76%; SNVs only: 28/31, 90%). A subset of driver mutations (eg. in ESR1, PIK3CA, ERBB2, EGFR) were observed in plasma but not tissue. Clonal variants in tissue were more likely to be detected in plasma than subclonal variants (p<.001). Conclusions: This novel, high-intensity ctDNA assay enabled broad detection of genomic variants in plasma at high rates of concordance with corresponding tumor tissue, providing strong evidence for tumor-derivation of these signals. This study will inform development of a high-intensity sequencing approach for early cancer detection.

Kinetics of IL-2 and IL-4 mRNA and protein production by graft-infiltrating lymphocytes responsible for rejection after clinical heart transplantation

1997 ◽  
Vol 5 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Carla C Baan ◽  
Nicole M van Besouw ◽  
Cornelis R. Daane ◽  
Aggie HMM Balk ◽  
Bas Mochtar ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Protein Production ◽  
Infiltrating Lymphocytes ◽  
Kinetics Of

scholarly journals Enzyme kinetics of CRISPR molecular diagnostics

2021 ◽  
Author(s):  
Ashwin Ramachandran ◽  
Juan G. Santiago
Keyword(s):  
Reaction Time ◽  
Enzyme Kinetics ◽  
Molecular Diagnostics ◽  
Analytical Solutions ◽  
Rapid Testing ◽  
Kinetics Parameters ◽  
Diagnostic Assays ◽  
Degree Of Reaction ◽  
Significant Interest ◽  
Kinetics Of

AbstractCRISPR diagnostic assays have gained significant interest in the last few years. This interest has grown rapidly during the current COVID-19 pandemic where CRISPR diagnostics have been frontline contenders for rapid testing solutions. This surge in CRISPR diagnostics research prompts the following question: What exactly are the achievable limits of detection and associated assay times enabled by the kinetics of Cas12 and Cas13 enzymes? To address this question, we here present a model based on Michaelis-Menten enzyme kinetics theory applied to Cas enzymes. We use the model to develop analytical solutions for reaction kinetics and develop back-of-the­ envelope criteria to validate and check for consistency in reported enzyme kinetics parameters. We applied our analyses to all studies known to us which report Michaelis-Menten-type kinetics data for CRISPR associated enzymes. These studies include all subtypes of Cas12 and Cas13 and orthologs. We found all studies but one clearly violate at least two of our three rules of consistency. We further use our model to explore ranges of reaction time scales and degree of reaction completion for practically relevant target concentrations applicable to CRISPR-diagnostic assays.

scholarly journals Influence of high heating rates on evolution of oxides on directed laser energy additively fabricated IN718

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Sangram Mazumder ◽  
Mangesh V. Pantawane ◽  
Narendra B. Dahotre
Keyword(s):  
Photoelectron Spectroscopy ◽  
Room Temperature ◽  
Experimental Approach ◽  
Laser Energy ◽  
Isothermal Treatment ◽  
Thermal Treatments ◽  
Heating Rates ◽  
Temperature Oxidation ◽  
Fe Oxides ◽  
Kinetics Of

AbstractThe effect of non-isothermal treatment in oxygen-containing air, via heating rates of 10, 50, and 1000 °C/min until 1000 °C followed by furnace cooling to room temperature on oxides formed on directed laser energy additively fabricated IN718 was studied. Another set of samples heated up to 1000 °C using the same heating rates were isothermally held at 1000 °C for 1 hr followed by furnace cooling to room temperature. X-ray photoelectron spectroscopy indicated the presence of NiO on samples only heated at 1000 °C/min. Also, results indicated the absence of Fe-oxides on non-isothermally treated samples, irrespective of heating rate. However, isothermal treatment confirmed the presence of NiO on all samples and Fe-oxides on samples heated via 50 and 1000 °C/min. The durations in complement with the kinetics of the thermal treatments influenced oxide evolution in the samples. Such an experimental approach was adopted to study the material response under dynamic short duration-high temperature oxidation.

Fluorescence-Based Measurement of Real-Time Kinetics of Protoporphyrin IX After 5-Aminolevulinic Acid Administration in Human In Situ Malignant Gliomas

Neurosurgery ◽  
2019 ◽  
Vol 85 (4) ◽  
pp. E739-E746 ◽  
Author(s):  
Sadahiro Kaneko ◽  
Eric Suero Molina ◽  
Christian Ewelt ◽  
Nils Warneke ◽  
Walter Stummer
Keyword(s):  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Protoporphyrin Ix ◽  
Time Dependency ◽  
Average Maximum ◽  
Kinetics Of ◽  
Acid Administration ◽  
Time Point

Abstract BACKGROUND Five-aminolevulinic acid (5-ALA) is well established for fluorescence-guided resections of malignant gliomas by eliciting the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. Because of the assumed time point of peak fluorescence, 5-ALA is recommended to be administered 3 h before surgery. However, the actual time dependency of tumor fluorescence has not yet been evaluated in humans and may have important implications. OBJECTIVE To investigate the time dependency of PpIX by measuring fluorescence intensities in tumors at various time points during surgery. METHODS Patients received 5-ALA (20 mg/kg b.w.) 3 to 4 h before surgery. Fluorescence intensities (FI) and estimated tumor PpIX concentrations (CPPIX) were measured in the tumors over time with a hyperspectral camera. CPPIX was assessed using hyperspectral imaging and by evaluating fluorescence phantoms with known CPPIX. RESULTS A total of 201 samples from 68 patients were included in this study. On average, maximum values of calculated FI and CPPIX were observed between 7 and 8 h after 5-ALA administration. FI and CPPIX both reliably distinguished central strong and marginal weak fluorescence, and grade III compared to grade IV gliomas. Interestingly, marginal (weak) fluorescence was observed to peak later than strong fluorescence (8-9 vs 7-8 h). CONCLUSION In human in Situ brain tumor tissue, we determined fluorescence after 5-ALA administration to be maximal later than previously thought. In consequence, 5-ALA should be administered 4 to 5 h before surgery, with timing adjusted to internal logistical circumstances and factors related to approaching the tumor.

Interfacial reactions in multilayers intended for microelectronics devices

1998 ◽  
Vol 514 ◽  
Author(s):  
X. Federspiel ◽  
F. Voiron ◽  
M. Ignat ◽  
T. Marieb ◽  
H. Fujimoto
Keyword(s):  
Phase Formation ◽  
Reaction Rate ◽  
Experimental Approach ◽  
Intermetallic Phase ◽  
Activation Energies ◽  
Interfacial Reactions ◽  
Scanning Calorimetry ◽  
Back Scattering ◽  
Apparent Activation Energies ◽  
Kinetics Of

ABSTRACTThe knowledge of the reaction kinetics which can occur at an interface of a couple of materials, remains a crucial issue to establish the structural limits of a diffusion barrier intended for microelectronic structures.In the past years, the interfacial reactions activated at an interface of a couple of materials, as for example aluminum and titanium, have been analyzed extensively using different experimental tools, as for example: Ruthreford Back Scattering (thickness determination) and Differential Scanning Calorimetry (DSC). Then, these experimental methods were useful to deduce parameters, characterizing the interfacial reactions in bulk samples: apparent activation energies, enthalpy of formation. Because in thin films, the kinetics of the reactions that can be activated at an interface will be different; we studied interfacial reactions in submicronic Al/Ti layers.Taking advantage of the accuracy of the DSC (reaction rate determinations and detection of earlier stages of intermetallic phase formation), our experimental approach consisted in a series of isothermal and non-isothermal DSC experiments on submicron Al/Ti layered structures. From the reaction rate determination, analytical methods as the Kissinger Ozawa approach were used, to determine the apparent activation energies of the phase formation. Also the results allowed to model and discuss the first steps of the interfacial reaction.

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