gebhart/patrepeval huggingface dataset:
Microfluidic Immiscible Phase Filtration System for the Isolation of Small Numbers of Cells from Whole Blood (2019)

Isolation of circulating tumor cells (CTCs) has generated clinical and academic interest due to the important role that CTCs play in cancer metastasis and diagnosis. Here, we present a PDMS and glass prototype of a microfluidic device for the immunomagnetic, immiscible phase filtration based capture, and isolation of MCF-7 breast cancer cells, from various sample matrices including PBS-based buffer, blood plasma, and unprocessed whole blood. Following optimization of surface energy of an oil-water interface, microfluidic geometry, and bead-binding kinematics, our microfluidic device achieved 95 ± 4% recovery of target cells from PBS-based buffer with 95% purity, 90 ± 3% recovery of target cells from blood plasma and recovery of ~70 ± 5% from unprocessed whole blood with purity >99% with 1 ml blood samples with 1,000 spiked target cells. From quantitative studies to assess the nonspecific carryover of contaminants from whole blood, we found that our system accomplishes a >175 fold depletion in platelets, >900 fold depletion in erythrocytes, and >1,700 fold depletion in leukocytes with respect to unprocessed whole blood, enabling us to avoid sample pre-processing. In addition, we found that ~95% of the isolated target cells were viable, making them suitable for subsequent molecular and cellular studies. We quantify and propose mechanisms for the carryover of platelet, erythrocyte, and leukocyte contamination in purified samples, rather than relying on sample pre-processing. These results validate the continued study of our platform for extraction of CTCs from patient samples and other rare cell isolation applications. © 2019 International Society for Advancement of Cytometry.
A neural network model for the formation of topographic maps in the CNS: development of receptive fields (1990)

A discussion is presented of the properties of the model in the high-dimensional limit. The authors present results from a Monte Carlo simulation indicating a facilitation of the map-ordering process if the dimensionality of the input space is increased, and they provide a mathematical analysis of the development of localized receptive fields via the input-selection mechanism. The analytical results are compared with data from large-scale simulations using a Connection Machine CM-2, and very good agreement is found
ChemInform Abstract: Synthetic Peptide Libraries (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Measuring perfusion and bioenergetics simultaneously in mouse skeletal muscle: a multiparametric functional‐NMR approach (2010)

A totally noninvasive set-up was developed for comprehensive NMR evaluation of mouse skeletal muscle function in vivo. Dynamic pulsed arterial spin labeling-NMRI perfusion and blood oxygenation level-dependent (BOLD) signal measurements were interleaved with (31)P NMRS to measure both vascular response and oxidative capacities during stimulated exercise and subsequent recovery. Force output was recorded with a dedicated ergometer. Twelve exercise bouts were performed. The perfusion, BOLD signal, pH and force-time integral were obtained from mouse legs for each exercise. All reached a steady state after the second exercise, justifying the pointwise summation of the last 10 exercises to compensate for the limited (31)P signal. In this way, a high temporal resolution of 2.5 s was achieved to provide a time constant for phosphocreatine (PCr) recovery (τ(PCr)). The higher signal-to-noise ratio improved the precision of τ(PCr) measurement [coefficient of variation (CV) = 16.5% vs CV = 49.2% for a single exercise at a resolution of 30 s]. Inter-animal summation confirmed that τ(PCr) was stable at steady state, but shorter (89.3 ± 8.6 s) than after the first exercise (148 s, p < 0.05). This novel experimental approach provides an assessment of muscle vascular response simultaneously to energetic function in vivo. Its pertinence was illustrated by observing the establishment of a metabolic steady state. This comprehensive tool offers new perspectives for the study of muscle pathology in mice models.
Photon migration through fetal head &lt;italic&gt;in utero&lt;/italic&gt; using continuous wave, near-infrared spectroscopy: development and evaluation of experimental and numerical models (2000)

In this work experimental tissue phantoms and numerical models were developed to estimate photon migration through the fetal head in utero. The tissue phantoms incorporate a fetal head within an amniotic fluid sac surrounded by a maternal tissue layer. A continuous wave, dual-wavelength (lambda = 760 and 850 nm) spectrometer was employed to make near-infrared measurements on the tissue phantoms for various source-detector separations, fetal-head positions, and fetal-head optical properties. In addition, numerical simulations of photon propagation were performed with finite-difference algorithms that provide solutions to the equation of radiative transfer as well as the diffusion equation. The simulations were compared with measurements on tissue phantoms to determine the best numerical model to describe photon migration through the fetal head in utero. Evaluation of the results indicates that tissue phantoms in which the contact between fetal head and uterine wall is uniform best simulates the fetal head in utero for near-term pregnancies. Furthermore, we found that maximum sensitivity to the head can be achieved if the source of the probe is positioned directly above the fetal head. By optimizing the source-detector separation, the signal originating from photons that have traveled through the fetal head can drastically be increased.
Isoform-spezifische Funktionen mitogen-aktivierter Proteinkinasen in Transkriptionskontrolle und Proliferation (2011)

In vielen humanen Neoplasien findet sich eine erhöhte Aktivität des Raf-Mek-Erk-Signaltransduktionsweges. Zunächst wurde davon ausgegangen, dass diese erhöhte Aktivität hauptsächlich durch die Ras-Onkogene hervorgerufen wird. Doch mittlerweile konnten auch Mutationen der Raf Gene in humanen Neoplasien nachgewiesen werden. Gegen Raf und Mek konnten eine Anzahl von Enzyminhibitoren entwickelt werden. Der Nachteil vieler dieser Inhibitoren ist, dass sie nicht zwischen den einzelnen Kinaseisoformen unterscheiden können. In dieser Arbeit ist es nun das erste Mal gelungen, jede Komponente des Raf-Mek-Erk-Signaltransduktionsweges einzeln mittels RNA Interferenz effizient zu inhibieren. Dabei konnte die Rolle der verschiedenen Isoformen in der Proliferation, Morphologie und Genex-pression von transformierten Zellen definiert werden. In den NIH3T3-pEJ Zellen konnte A-Raf erstmals eine antiapoptotische Rolle zugewiesen werden. Diese Hemmung der Apoptose läuft möglicherweise über einen Mek2-abhängigen Weg und ist an die Mitochondrien gekoppelt. Für die beiden Mek Kinasen konnten unter-schiedliche Funktionen in der Signalweiterleitung gezeigt werden. Mek2 spielt die Hauptrolle in der Aktivierung der beiden Substratkinasen Erk1 und Erk2. Der Verlust der Mek1 Isoform wird dagegen möglicherweise durch eine erhöhte Expression von Mek2 kompensiert und wirkt sich nicht so stark auf die Phosphorylierung von Erk1/2 aus. Durch die Verwendung von Erk1 und Erk2 spezifischen siRNAs konnte eine Trennung zwischen der Proliferationsre-gulation und der Kontrolle der morphologischen Transformation herausgearbeitet werden. Durch die Verwendung von Mikroarrays ist es gelungen, beiden Phänotypen ein Genexpres-sionsprofil zuzuordnen. Neben Unterschieden zwischen den verschiedenen Kinaseisoformen konnten neue, potentielle Feedbacks beschrieben werden.
Combined Inhibition of Fyn and c-Src Protects Hippocampal Neurons and Improves Spatial Memory via ROCK after Traumatic Brain Injury (2022)

Our previous studies demonstrated that traumatic brain injury (TBI) and ventricular administration of thrombin caused hippocampal neuron loss and cognitive dysfunction via activation of Src family kinases (SFKs). Based on SFK localization in brain, we hypothesized SFK subtypes Fyn and c-Src, as well as SFK downstream molecule Rho-associated protein kinase (ROCK), contribute to cell death and cognitive dysfunction after TBI. We administered nanoparticle wrapped small interfering RNA (siRNA)-Fyn and siRNA-c-Src, or ROCK inhibitor Y-27632 to adult rats subjected to moderate lateral fluid percussion (LFP)-induced TBI. Spatial memory function was assessed from 12 to 16 days, and NeuN stained hippocampal neurons were assessed 16 days after TBI. The combination of siRNA-Fyn and siRNA-c-Src, but neither alone, prevented hippocampal neuron loss and spatial memory deficits after TBI. The ROCK inhibitor Y-27632 also prevented hippocampal neuronal loss and spatial memory deficits after TBI. The data suggest that the combined actions of three kinases (Fyn, c-Src, ROCK) mediate hippocampal neuronal cell death and spatial memory deficits produced by LFP-TBI, and that inhibiting this pathway prevents the TBI-induced cell death and memory deficits.
Cytokine changes in patients with heatstroke during pilgrimage to Makkah (1997)

Circulating levels and role of IL-6, IL-1ra, TNFsr-II and CRP in patients with heatstroke is not fully known. This study correlated levels of these mediators with outcome in 26 patients. In survivors (n=20), IL-6 concentration declined on cooling, whereas in non-survivors levels continued to increase at 6 h following admission before declining. Admission TNFsr-II concentrations in survivors were significantly lower than non-survivors and levels continued to rise in both groups. IL-1ra levels were markedly elevated in both groups. Changes in cytokine levels were not influenced by renal function. Elevated C-reactive protein levels were observed for both groups and remained so despite cooling, furthermore, there was no correlation with alanine aminotransferase levels. The study demonstrated the elevation of the above mediators and suggested a role in the pathogenesis of heatstroke. Markedly elevated levels or those that remained elevated despite cooling were associated with mortality.
Simulation studies of lateral and opposed contact GaAs photoconductive switch geometry for high power, UWB microwave applications (1998)

Summary form only given. The high-gain GaAs Photoconductive semiconductor switch (PCSS) has been studied, using a laser beam as the triggering source. The switch is an integrated component of a parallel plate radiation source, used for driving a TEM horn impulse-radiating antenna. Specifically, the response of a trap filled semiconductor with varying contact placements (lateral and opposed) and material properties have been simulated. The objectives are to identify parameters that would optimize the switch lifetime and hold-off voltage. Beam power and its incidence locations were also varied during the simulation process.
Doxorubicin‐Loaded Physalis Mottle Virus Particles Function as a pH‐Responsive Prodrug Enabling Cancer Therapy (2020)

The controlled release of drugs using nanoparticle-based delivery vehicles is a promising strategy to improve the safety and efficacy of chemotherapy. A simple, scalable, and reproducible strategy is developed to synthesize a drug delivery system (DDS) by loading 6-maleimidocaproyl-hydrazone doxorubicin (DOX-EMCH) into the empty core of virus-like particles (VLPs) derived from Physalis mottle virus (PhMV) via a combination of chemical conjugation to cysteine residues and π-π stacking interactions with the anchored doxorubicin molecule. The DOX-EMCH prodrug features an acid-sensitive hydrazine linker that triggers the release of doxorubicin in the slightly acidic extracellular tumor microenvironment or acidic endosomal or lysosomal compartments following cellular uptake. The VLP external surface is coated with polyethylene glycol (PEG) to prevent non-specific uptake and improve biocompatibility. The DOX-PhMV-PEG particles are stable in vitro and show greater efficacy in vivo compared to free doxorubicin in a breast tumor mouse model (using MDA-MB-231 cells and nude mice): 92% of the tumor-bearing mice treated with DOX-PhMV-PEG are completely cured compared to 27% of those treated with free doxorubicin under the same conditions, representing a 3.4-fold improvement. These results lay a foundation for the further development of this biological drug delivery system for a new generation of chemotherapy products.
Supplementary Table 1 from Endobronchial miRNAs as Biomarkers in Lung Cancer Chemoprevention (2023)

&lt;p&gt;PDF file - 37K, Distribution of histologies at BL and FU between the treatment arms and stratified by smoking status Legend: N=number, pts=patients&lt;/p&gt;
Impact of wavelet basis on vibration analysis for rolling bearing defect diagnosis (2011)

This paper presents a quantitative approach to evaluate the impact of wavelet basis on vibration analysis of rolling bearings based on cross-correlation measure. As a basic tool to investigate the relationship between two data sequences from the viewpoint of statistics, the cross-correlation analysis is able to characterize the performance difference among various wavelet bases when analyzing the vibration signals. Experimental study has verified that the cross-correlation measure provides quantitative guidance to selecting base wavelet for better defect diagnosis of rolling bearings.
The large size telescope of the Cherenkov Telescope Array (2014)

The Cherenkov Telescope Array (CTA) project aims to implement the world's largest next generation of Very High Energy gamma-ray Imaging Atmospheric Cherenkov Telescopes devoted to the observation from a few tens of GeV to more than 100 TeV. To view the whole sky, two CTA sites are foreseen, one for each hemisphere. The sensitivity at the lowest energy range will be dominated by four Large Size Telescopes, LSTs, located at the center of each array and designed to achieve observations of high red-shift objects with the threshold energy of 20 GeV. The LST is optimized also for transient low energy sources, such as Gamma Ray Bursts (GRB), which require fast repositioning of the telescope. The overall design and the development status of the first LST telescope will be discussed.
Cardiac Health Risk Stratification System (CHRiSS): A Bayesian-Based Decision Support System for Left Ventricular Assist Device (LVAD) Therapy (2014)

This study investigated the use of Bayesian Networks (BNs) for left ventricular assist device (LVAD) therapy; a treatment for end-stage heart failure that has been steadily growing in popularity over the past decade. Despite this growth, the number of LVAD implants performed annually remains a small fraction of the estimated population of patients who might benefit from this treatment. We believe that this demonstrates a need for an accurate stratification tool that can help identify LVAD candidates at the most appropriate point in the course of their disease. We derived BNs to predict mortality at five endpoints utilizing the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database: containing over 12,000 total enrolled patients from 153 hospital sites, collected since 2006 to the present day, and consisting of approximately 230 pre-implant clinical variables. Synthetic minority oversampling technique (SMOTE) was employed to address the uneven proportion of patients with negative outcomes and to improve the performance of the models. The resulting accuracy and area under the ROC curve (%) for predicted mortality were 30 day: 94.9 and 92.5; 90 day: 84.2 and 73.9; 6 month: 78.2 and 70.6; 1 year: 73.1 and 70.6; and 2 years: 71.4 and 70.8. To foster the translation of these models to clinical practice, they have been incorporated into a web-based application, the Cardiac Health Risk Stratification System (CHRiSS). As clinical experience with LVAD therapy continues to grow, and additional data is collected, we aim to continually update these BN models to improve their accuracy and maintain their relevance. Ongoing work also aims to extend the BN models to predict the risk of adverse events post-LVAD implant as additional factors for consideration in decision making.
Table S2 from Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression (2023)

&lt;p&gt;Data collection and refinement statistics (molecular replacement)&lt;/p&gt;
In-vivo longitudinal imaging of microvascular changes in irradiated oral mucosa of radiotherapy cancer patients using optical coherence tomography (2017)

Mucositis is the limiting toxicity of radio(chemo)therapy of head and neck cancer. Diagnostics, prophylaxis and correction of this condition demand new accurate and objective approaches. Here we report on an in vivo longitudinal monitoring of the oral mucosa dynamics in 25 patients during the course of radiotherapy of oropharyngeal and nasopharyngeal cancer using multifunctional optical coherence tomography (OCT). A spectral domain OCT system with a specially-designed oral imaging probe was used. Microvasculature visualization was based on temporal speckle variations of the full complex signal evaluated by high-pass filtering of 3D data along the slow scan axis. Angiographic image quantification demonstrated an increase of the vascular density and total length of capillary-like-vessels before visual signs or clinical symptoms of mucositis occur. Especially significant microvascular changes compared to their initial levels occurred when grade two and three mucositis developed. Further, microvascular reaction was seen to be dose-level dependent. OCT monitoring in radiotherapy offers a non-invasive, convenient, label-free quantifiable structural and functional volumetric imaging method suitable for longitudinal human patient studies, furnishing fundamental radiobiological insights and potentially providing useful feedback data to enable adaptive radiotherapy (ART).
Investigation of peptomimetics of GD2 antibodies as targeted therapy against human small cell lung cancer in-vitro (2006)

13128 Background: GD2 is a well-established target that has been validated for neuroblastoma and small cell lung cancer. The therapeutic and diagnostic use of monoclonal antibodies directed to GD2 in small cell lung cancer is well documented. It has been shown that the binding of GD2 monoclonal antibodies alone can induce growth suppression and cell death of small cell lung cancer cells in-vitro. Our laboratory has developed synthetic small molecule peptomimetics as ligands of GD2. Peptomimetics have favorable in-vivo pharmacological properties compared to antibodies with no immunogenicity, longer half-lives, low toxicity, good tissue penetration, biodistribution and high target selectivity. This study proposed to determine the efficacy of peptomimetics of GD2 antibodies against small cell lung cancer cells in-vitro. Methods: 2 human cell lines were studied. H69 is a classic small cell lung cancer and H82 is a morphological variant small cell lung cancer both of which have been reported in the literature to express GD2. Cell surface expression of ganglioside GD2 was analyzed by flow cytometry (FACScan, BD Biosciences) using GD2 mAB 3F8 and GD2 mAB ME361. Cell proliferation was assessed using standard MTT assays with serum containing medium and cultured for approximately 3 doubling times for each cell line. The cell lines were exposed to increasing doses of GD2 specific peptomimetic to a maximum of 25 uM with controls including serum containing media with and without a GD2 negative peptomimetic and assessed for cell proliferation. Results: GD2 expression was confirmed for both cell lines- H69 and H82 using FACs. Exposure of the GD2 specific peptomimetic clearly caused growth suppression on the range of 35–40% when compared to controls. A dose response relationship was demonstrated with a plateau beyond 10 uM concentrations. Each experiment repeated ≥ 3 occasions. Conclusions: We have shown that attachment of GD2 specific peptomimetics can cause decreased cell proliferation in 2 small cell lung cancer cell lines H69 and H82. We have shown that there is a dose response relationship by which these compounds reduce cell viability. Peptomimetics of GD2 antibodies show promise as a targeted therapy for small cell lung cancer in-vitro and warrant further study. [Table: see text]
Preclinical pharmacokinetics and biodistribution studies of 89Zr-labeled pembrolizumab for human dosimetry estimation (2016)

1023 Objectives Pembrolizumab is a clinically-available humanized monoclonal antibody that targets programmed cell death protein (PD-1) on the surface of activated T and B cells. Currently, pembrolizumab is approved for the treatment of advanced melanoma and non-small cell lung cancer. In some instances, severe toxicities have been detected in patients treated with pembrolizumab, which have been linked to the accumulation of antibody in off-target tissues. In this study, we evaluate the pharmacokinetics, biodistribution, and dosimetry of pembrolizumab in vivo using positron emission tomography (PET) imaging. Methods Pembrolizumab was conjugated with the chelator desferrioxamine (Df) before radiolabeling with the long-lived isotope 89Zr (t1/2 = 3.3 days). Long-term whole-body tracking of the radiolabeled antibody was accomplished in three rodent models, including Balb/c mice, Sprague Dawley rats, and PBL mice (NSG mice reconstituted with human peripheral blood mononuclear cells). Data obtained from PET scans and biodistribution studies were extrapolated to predict radiation dose estimates for humans. Results 89Zr-Df-Pembrolizumab stayed in circulation throughout the study and accumulated the greatest in liver (3.40±0.68 %ID/g for mice and 0.87±0.06 %ID/g for rats at 168 h p.i.) and spleen tissues (4.10±0.41 %ID/g mice and 0.71±0.05 %ID/g rats). Relatively high doses were estimated to these organs (0.958±0.077 mGy/MBq for the liver and 0.109±0.103 mGy/MBq for spleen using rat data) as well as to the urinary bladder wall (0.578±0.006 mGy/MBq), resulting from the initial clearance routes of this agent. Despite these high uptakes, the total body absorbed doses for humans were found to be within safe limits, at a total body effective dose of 0.540±0.008 mSv/MBq. The use of PBL mice allowed for a more clinically relevant comparison to be made. Conclusions The low total body and major organ doses found in this study indicate the potential use of 89Zr-Df-Pembrolizumab for the clinical selection of patients that may benefit from anti-PD-1 therapy and the development of more advanced dosing strategies in the future. The techniques in this study may be further applied to other antibodies for better understanding of the pharmacokinetics, biodistributions, and dosimetry for future clinical applications.