gebhart/patrepeval huggingface dataset:
Microbial activation converts neutrophils into anti-tumor effectors (2020)

ABSTRACT Neutrophils infiltrate most solid tumors and their presence is usually correlated with suppression of anti-tumor responses, metastasis and poor prognosis. Here we used microbial bioparticles administered into the tumor microenvironment to transform neutrophils into anti-tumor effectors. Microbially activated neutrophils acquired an effector phenotype associated with pathogen killing and lost vascular endothelial growth factor expression associated with tumor growth and metastasis. They became the dominant immune cell infiltrating the tumor and inhibited tumor growth. Using intravital two-photon microscopy microbially activated neutrophils could be seen forming close contacts with tumor cells resulting in tumor tissue remodeling and tumor cell death. Thus, microbial bioparticle treatment can endow neutrophils with anti-tumor properties, suggesting that neutrophil plasticity in cancer could be exploited for tumor killing. These data highlight a pathway for the rational development of neutrophil-based cancer therapy.
Fenix – personalized information filtering system for WWW pages (2001)

Nowadays the Internet offers a large amount of information to a wide range of users, making it difficult to deal with. The present work suggests the use of intelligent agents for the personalized filtering of Web pages. A set of autonomous, non‐mobile and adaptive agents was developed, aiming to satisfy the user’s need for information. The agents learn from the users’ feedback and attempt to produce better results over time. This work presents the system description and the promising results of tests performed in a simulated environment. The proposed system has proven to be a useful tool in reducing the amount of information with which the user has to deal.
A Technique for Correction of Equinus Contracture Using a Wire Fixator and Elastic Tension (2006)

Equinus contracture often is a complication of trauma, burns, or neurologic deficit. Many patients with contractures secondary to trauma or burns have poor soft tissue, which makes invasive correction a less appealing option. The Ilizarov external fixator has been used as a less invasive attempt to correct equinus contracture. We describe our "dynamic" technique and present a clinical patient series using a variation of the unconstrained Ilizarov technique, which uses elastic bands rather than threaded rods to supply the corrective force.
Massive Crossover Suppression by CRISPR-Cas-mediated Plant Chromosome Engineering (2022)

Abstract Recent studies have demonstrated that not only genes, but also entire chromosomes can be engineered using CRISPR-Cas9 1–5. A major objective of applying chromosome restructuring (CR) in plant breeding is the manipulation of genetic exchange 6. Here we show that meiotic recombination can be suppressed in nearly the entire chromosome using CR. We were able to induce a heritable inversion of a more than 17 Mb-long chromosome fragment, which contained the centromere and covered most of chromosome 2 of the Arabidopsis ecotype Col-0. Only the 2 and 0.5 Mb-long telomeric ends remained in their original orientation. In SNP marker analysis with the offspring of crosses with the ecotype Ler-1, we detected a massive reduction of crossovers (CO) within the inverted chromosome region, coupled with a shift of CO to the telomeric ends. Interestingly, the few genetic exchanges detected within the inversion all originated from double CO. This not only indicates that heritable genetic exchange can occur by interstitial chromosome pairing, but also that it is restricted to the production of viable progeny.
On the origins of the universal dynamics of endogenous granules in mammalian cells. (2009)

Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics--both of which are crucial for the interpretation of the results from MPTM technique--are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms--molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dynamics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.
A practical access to acyl radicals from acyl hydrazides (2002)

Various acyl radicals can be generated from the corresponding acyl triphenylmethyldiazo derivatives, produced by in situ oxidation of hydrazide precursors with phenylseleninic acid.
Nano-spectroscopic imaging of intermolecular structure, coupling and dynamics (2013)

Molecular self-assembly, the function of biomembranes, and the performance of organic solar cells rely on molecular interactions on the nanoscale. The understanding and design of such intrinsic or engineered heterogeneous functional soft matter has long been impeded by a lack of spectroscopic tools with sufficient nanometer spatial resolution, attomolar sensitivity, and intermolecular spectroscopic specificity. We implement vibrational scattering-scanning near-field optical microscopy ($s$-SNOM) in a multi-spectral modality with unprecedented spectral precision to investigate the structure-function relationship in nano-phase separated block-copolymers. We use a vibrational resonance as a sensitive reporter of the local chemical environment and resolve, with few nanometer spatial resolution and 0.2 cm$^{-1}$ spectral precision, spectral Stark shifts and line broadening correlated with molecular-scale morphologies. By creating images of solvatochromic vibrational shifts we discriminate local variations in electric fields between the core and interface regions of the nano-domains with quantitative agreement to dielectric continuum models. This new nano-chemometric ability to directly resolve nanoscale morphology and associated intermolecular interactions can form a basis for the systematic control of functionality in multicomponent soft matter systems.
Endoscopic retrograde cholangiopancreatography (ERCP) (2009)

Journal Article
Data from MEK Inhibition, Alone or in Combination with BRAF Inhibition, Affects Multiple Functions of Isolated Normal Human Lymphocytes and Dendritic Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;Combination therapy with BRAF and MEK inhibition is currently in clinical development for the treatment of BRAF-mutated malignant melanoma. BRAF inhibitors are associated with enhanced antigen-specific T-lymphocyte recognition &lt;i&gt;in vivo&lt;/i&gt;. Consequently, BRAF inhibition has been proposed as proimmunogenic and there has been considerable enthusiasm for combining BRAF inhibition with immunotherapy. MEK inhibitors inhibit ERK phosphorylation regardless of BRAF mutational status and have been reported to impair T-lymphocyte and modulate dendritic cell function. In this study, we investigate the effects on isolated T lymphocytes and monocyte-derived dendritic cells (moDC) of a MEK (trametinib) and BRAF (dabrafenib) inhibitor combination currently being evaluated in a randomized controlled clinical trial. The effects of dabrafenib and trametinib, alone and in combination, were studied on isolated normal T lymphocytes and moDCs. Lymphocyte viability, together with functional assays including proliferation, cytokine production, and antigen-specific expansion, were assessed. MoDC phenotype in response to lipopolysaccharide stimulation was evaluated by flow cytometry, as were effects on antigen cross-presentation. Dabrafenib did not have an impact on T lymphocytes or moDCs, whereas trametinib alone or in combination with dabrafenib suppressed T-lymphocyte proliferation, cytokine production, and antigen-specific expansion. However, no significant decrease in CD4&lt;sup&gt;+&lt;/sup&gt; or CD8&lt;sup&gt;+&lt;/sup&gt; T-lymphocyte viability was observed following kinase inhibition. MoDC cross-presentation was suppressed in association with enhanced maturation following combined inhibition of MEK and BRAF. The results of this study demonstrate that MEK inhibition, alone or in combination with BRAF inhibition, can modulate immune cell function, and further studies &lt;i&gt;in vivo&lt;/i&gt; will be required to evaluate the potential clinical impact of these findings. &lt;i&gt;Cancer Immunol Res; 2(4); 351–60. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Unconventional Multiple Fracture Treatments Using Dynamic Diversion and Downhole Mixing (2002)

This paper reviews a unique, relatively new stimulation process that uses dynamic fluid energy (instead of mechanical methods) to isolate treatment fluid flow to a specific fracture point along the wellbore. A process of hydrajet-fracturing has been developed by merging four existing technologies: hydrajetting, hydraulic fracturing, jet pump technology, and dual-path fluid injection. These have been meshed to create a method whereby a wellbore is perforated (if necessary) and a fracture is initiated and placed accurately at a specific location, and then soon repeated at another chosen location uphole, or closer to the heel when in a lateral wellbore. The process was later expanded as a hydrojet-squeeze stimulation method also, even to the point of applying both of these applications while stimulating a single wellbore.This process employs two independent fluid streams: one in the treating string and another in the annulus. As these fluid paths will be supplied with separate pumping equipment, we have the option to instantaneously alter the downhole mixture that is being used to treat the formation at the current location of the jetting tool. An additional use of this two-stream feature is the capability to pump two different fluids that can be mixed downhole with a tremendously high energy to form a homogenous mixture at the fracture entry point, even creating foamed fluids insitu for some applications.This technique has been used to stimulate more than 50 horizontal or highly deviated wells (and a few vertical wells) as of the preparation of this paper, both proppant-laden fractures and fracture acidizing treatments. On average, more than 7 fractures were placed along a typical horizontal wellbore, typically several hundred feet apart without the use of mechanical sealing equipment. Additionally, numerous horizontal wells with higher permeabilities have been stimulated using the hydrajet-squeeze process alone.The diversion process follows a dynamic isolation approach that uses a high-velocity, high-energy jetted fluid. The process was originally developed for its unique stimulation capabilities in openhole horizontal wells, but has been extended to wells that have cemented or non-cemented liners, whether vertical, deviated, or horizontal and even to multilateral completions (or recompletions).This paper offers insight into many of these treatments, including the different well situations, design considerations, operations, and available results of the treatments. Possible unconventional approaches using this concept and a unique implementation in the field are also discussed.
Improving the Reactive Current Compensation Capability of Cascaded H-Bridge Based STATCOM Under Unbalanced Grid Voltage (2019)

This paper deals with the operation of a cascaded H-bridge (CHB) converter-based STATCOM under unbalanced grid conditions. Degrees of freedom and operational limitations of the CHB STATCOM during unbalanced grid condition are analyzed according to the converter power flow equations. Based on this analysis, an improved low-voltage ride-through (LVRT) strategy for the CHB STATCOM is proposed. In this strategy, the grid operator can control both the positive- and negative-sequence reactive currents independently within the operation range of the CHB STATCOM. In addition, to keep the submodules' capacitors voltages balanced, a zero-sequence voltage term is injected to the converter legs. The negative-sequence active current is also controlled to limit the injected zero-sequence voltage and keep the converter within the rated operation range. The performance and effectiveness of the proposed method are validated through PSCAD/EMTDC simulation of a 21-level CHB STATCOM. The results are experimentally demonstrated on a 9-level CHB STATCOM prototype.
A magneto-optical trap loaded from a pyramidal funnel (1998)

We have demonstrated the transfer of 39 K and 40 K atoms from a magneto-optical funnel (a hollow pyramidal mirror) through a low (0:05 l/s) conductance hole and into a conventional magneto-optical trap (mot) 35 cm away, with an efficiency of approximately six percent. This simple scheme should be useful for experiments requiring high loading rates with minimal contamination from hot untrapped atoms.
[Detection of antibodies against the virus causing viral gastroenteritis in swine using the modified autoradiography test]. (1982)

A modified method for autoradiographic determination of antibodies to the virus of transmissible gastroenteritis of swine was developed. It is based on the actual reaction between antigen bound in cells of the infected cell cultures and antibodies in tested sera, which is visualized, by help of rabbit antibodies marked 125J (125J RaSw IgG antibody) to porcine IgG, on a sensitive radiograph and evaluated on the basis of darkening at the point of positive immunological reaction. Specificity of the test and mutual comparability and reproducibility of the results were confirmed by examining the known positive and negative sera and by comparison with the results of the virus-neutralisation test. Out of the 36 examined porcine blood sera the antibodies were proved autoradiographically only in the samples positive also by virus-neutralisation. In experimentally infected pigs, the same dynamics of antibody production was recorded by the two tests. They were, however, demonstrated autoradiographically already by the two tests. They were, however, demonstrated autoradiographically already the eighth day after infection, while by virus neutralisation test as late as 14th day. Their level increased gradually until 35th day after infection.
Commercialization of methyl ester sulfonates (2005)

Because methyl ester sulfonates(MES)can be made from low cost vegetable and animal fats,production of methyl ester sulfonates has been studied for over30years.However,early efforts to manufacture MES resulted in products with high color and low conversion of methyl ester(ME)feedstock to MES.Dark color is undesirable because consumers equate light colors with product purity.Therefore,light color is mandatory if MES is to become a replacement for traditional surfactants in consumer products.Low conversion of ME to MES is an economic issue as it efˉfectively increases the cost of MES.The principle conversion problem has been the breaking of the ester bond in MES to form methanol and alpha sulfo sodium carboxylate(di-salt).Di-salt does not have good surfactant properties and is viewed as a yield loss.A solution to the color and di-salt problems was an essential condition for commercial utilization of MES.
Development of Zr-loaded Green-emitting Liquid Scintillator for Detection of Neutrinoless Double Beta Decay (2021)

In this study, zirconium acetylacetonate (Zr(acac) 4 ) containing the isotope 96 Zr was studied as a liquid scintillator for the possible detection of neutrinoless double beta decay. To avoid the absorption of scintillation by ligand absorption, the phosphor Coumarin 7 was assessed as a green-emitting liquid scintillator. By dissolving 3 g/L of Coumarin 7 in anisole, a liquid scintillator with a light yield of 12000 photons/MeV was fabricated. Subsequently, the liquid scintillator was loaded with Zr(acac) 4 . In the liquid scintillator containing 10 wt% Zr(acac) 4 , the light yield of scintillation was 370 photons/MeV for a blue-emitting liquid scintillator, while a light yield of 1900 photons/MeV was determined for a green-emitting liquid scintillator. The scintillation decay time constants of the fast component were around 4.4 ns. Liquid scintillators with a high light yield that avoid absorption by Zr(acac) 4 can be prepared using Coumarin 7.
Regulation of Prenatal Human Retinal Neurosphere Growth and Cell Fate Potential by Retinal Pigment Epithelium and Mash1 (2008)

During development of the central nervous system, stem and progenitor cell proliferation and differentiation are controlled by complex inter- and intracellular interactions that orchestrate the precise spatiotemporal production of particular cell types. Within the embryonic retina, progenitor cells are located adjacent to the retinal pigment epithelium (RPE), which differentiates prior to the neurosensory retina and has the capacity to secrete a multitude of growth factors. We found that secreted proteinaceous factors in human prenatal RPE conditioned medium (RPE CM) prolonged and enhanced the growth of human prenatal retinal neurospheres. The growth-promoting activity of RPE CM was mitogen-dependent and associated with an acute increase in transcription factor phosphorylation. Expanded populations of RPE CM-treated retinal neurospheres expressed numerous neurodevelopmental and eye specification genes and markers characteristic of neural and retinal progenitor cells, but gradually lost the potential to generate neurons upon differentiation. Misexpression of Mash1 restored the neurogenic potential of long-term cultures, yielding neurons with phenotypic characteristics of multiple inner retinal cell types. Thus, a novel combination of extrinsic and intrinsic factors was required to promote both progenitor cell proliferation and neuronal multipotency in human retinal neurosphere cultures. These results support a pro-proliferative and antiapoptotic role for RPE in human retinal development, reveal potential limitations of human retinal progenitor culture systems, and suggest a means for overcoming cell fate restriction in vitro.
Pharmacophore and Binding Analysis of Known and Novel B-RAF Kinase Inhibitors (2014)

The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type I 1/2 subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.
Clinical Validation of a PCR Assay for the Detection of EGFR Mutations in Non–Small-Cell Lung Cancer: Retrospective Testing of Specimens from the EURTAC Trial (2014)

The EURTAC trial demonstrated that the tyrosine kinase inhibitor (TKI) erlotinib was superior to chemotherapy as first-line therapy for advanced non-small cell lung cancers (NSCLC) that harbor EGFR activating mutations in a predominantly Caucasian population. Based on EURTAC and several Asian trials, anti-EGFR TKIs are standard of care for EGFR mutation-positive NSCLC. We sought to validate a rapid multiplex EGFR mutation assay as a companion diagnostic assay to select patients for this therapy. Samples from the EURTAC trial were prospectively screened for EGFR mutations using a combination of laboratory-developed tests (LDTs), and tested retrospectively with the cobas EGFR mutation test (EGFR PCR test). The EGFR PCR test results were compared to the original LDT results and to Sanger sequencing, using a subset of specimens from patients screened for the trial. Residual tissue was available from 487 (47%) of the 1044 patients screened for the trial. The EGFR PCR test showed high concordance with LDT results with a 96.3% overall agreement. The clinical outcome of patients who were EGFR-mutation detected by the EGFR PCR test was very similar to the entire EURTAC cohort. The concordance between the EGFR PCR test and Sanger sequencing was 90.6%. In 78.9% of the discordant samples, the EGFR PCR test result was confirmed by a sensitive deep sequencing assay. This retrospective study demonstrates the clinical utility of the EGFR PCR test in the accurate selection of patients for anti-EGFR TKI therapy. The EGFR PCR test demonstrated improved performance relative to Sanger sequencing.
Statistical Shape Model-Based Femur Kinematics From Biplane Fluoroscopy (2012)

Studying joint kinematics is of interest to improve prosthesis design and to characterize postoperative motion. State of the art techniques register bones segmented from prior computed tomography or magnetic resonance scans with X-ray fluoroscopic sequences. Elimination of the prior 3D acquisition could potentially lower costs and radiation dose. Therefore, we propose to substitute the segmented bone surface with a statistical shape model based estimate. A dedicated dynamic reconstruction and tracking algorithm was developed estimating the shape based on all frames, and pose per frame. The algorithm minimizes the difference between the projected bone contour and image edges. To increase robustness, we employ a dynamic prior, image features, and prior knowledge about bone edge appearances. This enables tracking and reconstruction from a single initial pose per sequence. We evaluated our method on the distal femur using eight biplane fluoroscopic drop-landing sequences. The proposed dynamic prior and features increased the convergence rate of the reconstruction from 71% to 91%, using a convergence limit of 3 mm. The achieved root mean square point-to-surface accuracy at the converged frames was 1.48 ± 0.41 mm. The resulting tracking precision was 1-1.5 mm, with the largest errors occurring in the rotation around the femoral shaft (about 2.5° precision).