gebhart/patrepeval huggingface dataset:
TU‐A‐141‐01: Multi Modal PET/CT Imaging for Therapy Response Early Prediction and Therapy Monitoring (2013)

Monitoring a patient's response during treatment plays an important role in optimizing personalized treatment strategy. It may offer the possibility to predict future response early during treatment and adapt therapy. It calls for an optimal use of existing and under development imaging technologies as well as image and data processing and analyses for characterizing tumor response. This lecture will provide an overview of three complementary points related to therapy response monitoring using PET/CT. The first one concerns the growing interest and potential future role of multi modal PET/CT imaging in response to therapy studies, from a clinical point of view. This will help the audience identifying which combinations of disease, associated treatments and radiotracers are concerned. The second point is associated with the technical issues and methodological requirements associated with implementing response to therapy monitoring in clinical studies, in terms of standardization and homogeneity of acquisition protocols (reproducibility) and optimal use of existing image reconstruction methods. Finally, the third point concerns the way produced images are exploited, processed and manually or semi‐automatically analyzed then integrated in multifactorial Decision Support Systems. Current and future trends in the development of advanced methods dedicated to facilitate processing and analysis of multi modal and sequential images PET/CT (and PET/MRI) will be discussed, as well as their potential future role for response to therapy monitoring based on multi modal imaging integrated with non imaging biomarkers of predictors. Learning Objectives 1. Review the current and future role of multi modal PET/CT imaging in early prediction and monitoring of response to therapy in several clinical oncology and radiotherapy applications. 2. Understand the requirements regarding standardization of imaging protocols and image generation in order to exploit multi modal image‐derived indices to characterize response to therapy. 3. Envision the future directions in developing semi automated methods for multi modal images analysis and multifactorial decision support systems integrating imaging and non imaging biomarkers.
Extracts from various mite species contain cross-reactive and noncross-reactive IgE epitopes. A RAST inhibition study. (1999)

Previous studies have demonstrated the high incidence of Dermatophagoides, Euroglyphus, Blomia, Lepidoglyphus and Chortoglyphus spp. sensitizations in a mite-allergic population. The aim of this study was to evaluate immunological cross-reactivity among the above mentioned groups, using sera from a nonrural population allergic to mites, from a subtropical area (Canary Islands). RAST inhibition studies demonstrated significant cross-reactivity among Dermatophagoides and Euroglyphus species (> or = 65% of maximum theoretical inhibition), as also noted by other authors. Blomia kulagini demonstrated scarce cross-reactivity with Dermatophagoides, Lepidoglyphus and Chortoglyphus species (< or = 30% of maximum theoretical inhibition) and medium level with Euroglyphus maynei (45% of maximum theoretical inhibition). Chortoglyphus arquatus demonstrated high cross-reactivity levels with the other species studied. The results obtained in this study demonstrated the scarce immunological cross-reactivity between Pyroglyphidae and non-Pyroglyphidae mites, thus suggesting the polysensitization of the studied population to different mite species.
Macromol. Rapid Commun. 10/2015 (2015)

Back Cover: The back cover image is a dramatization showing how nanobrick wall multilayer thin films could be used to protect tomatoes from oxidative degradation. These high gas barrier thin films are a polymer-based alternative to plastic films coated with metal and metal oxides, which are used for food, pharmaceutical, and electronics packaging. Further details can be found in the article by M. A. Priolo,* K. M. Holder, T. Guin, and J. C. Grunlan* on page 866.
Antitumor Effects of Immunotoxins Are Enhanced by Lowering HCK or Treatment with Src Kinase Inhibitors (2013)

Recombinant immunotoxins (RIT) are agents being developed for cancer treatment. They are composed of an Fv that binds to a cancer cell, fused to a 38-kDa fragment of Pseudomonas exotoxin A. SS1P is a RIT that targets mesothelin, a protein expressed on mesothelioma as well as pancreatic, ovarian, lung, and other cancers. Because the protein tyrosine kinase family regulates a variety of cellular processes and pathways, we hypothesized that tyrosine kinases might regulate susceptibility to immunotoxin killing. To investigate their role, we used siRNAs to lower the level of expression of the 88 known tyrosine kinases. We identified five tyrosine kinases, INSR, HCK, SRC, PDGFRβ, and BMX that enhance the activity of SS1P when their level of expression is lowered by siRNAs. We further investigated the Src family member HCK in this study. Knocking down of SRC slightly increased SS1P killing in A431/H9 cells, but knocking down HCK substantially enhanced killing by SS1P. We investigated the mechanism of enhancement and found that HCK knockdown enhanced SS1P cleavage by furin and lowered levels of Mcl-1 and raised Bax. We then found that Src inhibitors mimic the stimulatory effect of HCK knockdown; both SU6656 and SKI-606 (bosutinib) enhanced immunotoxin killing of mesothelin-expressing cells by SS1P and CD22-expressing cells by HA22 (moxetumomab pasudotox). SU6656 also enhanced the antitumor effects of SS1P and HA22 in mouse xenograft tumor models. Our data suggest that the combination of immunotoxin with tyrosine kinase inhibitors may be an effective way to treat some cancers.
Estimation of inelastic seismic material properties of a surficial sea‐bed from multi‐component marine seismic data (2010)

ABSTRACT To date, state‐of‐the‐art seismic material parameter estimates from multi‐component sea‐bed seismic data are based on the assumption that the sea‐bed consists of a fully elastic half‐space. In reality, however, the shallow sea‐bed generally consists of soft, unconsolidated sediments that are characterized by strong to very strong seismic attenuation. To explore the potential implications, we apply a state‐of‐the‐art elastic decomposition algorithm to synthetic data for a range of canonical sea‐bed models consisting of a viscoelastic half‐space of varying attenuation. We find that in the presence of strong seismic attenuation, as quantified by ‐values of 10 or less, significant errors arise in the conventional elastic estimation of seismic properties. Tests on synthetic data indicate that these errors can be largely avoided by accounting for the inherent attenuation of the seafloor when estimating the seismic parameters. This can be achieved by replacing the real‐valued expressions for the elastic moduli in the governing equations in the parameter estimation by their complex‐valued viscoelastic equivalents. The practical application of our parameter procedure yields realistic estimates of the elastic seismic material properties of the shallow sea‐bed, while the corresponding ‐estimates seem to be biased towards too low values, particularly for S‐waves. Given that the estimation of inelastic material parameters is notoriously difficult, particularly in the immediate vicinity of the sea‐bed, this is expected to be of interest and importance for civil and ocean engineering purposes.
Re: Acquired Platinum Resistance Enhances Tumour Angiogenesis Through Angiotensin II Type 1 Receptor in Bladder Cancer (2012)

No AccessJournal of UrologyInvestigative Urology1 Aug 2012Re: Acquired Platinum Resistance Enhances Tumour Angiogenesis Through Angiotensin II Type 1 Receptor in Bladder Cancer Anthony AtalaM.D. Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.04.045AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Acquired Platinum Resistance Enhances Tumour Angiogenesis Through Angiotensin II Type 1 Receptor in Bladder Cancer." The Journal of Urology, 188(2), p. 675 © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 188Issue 2August 2012Page: 675 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Metrics Author Information Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
Anti-tumor effects of L-type amino acid transporter 1 (LAT1) inhibitor in a syngeneic and orthotropic mouse model for melanoma (2019)

Melanoma is the most malignant form of skin cancer, which originates from the pigment-producing melanocytes in the basal layer of epidermis. L-type amino acid transporter 1 (LAT1) is an amino acid transporter that transports most of the essential amino acids. LAT1 is upregulated in various cancers, including melanoma, and contributes to supporting cancer cell proliferation. Therefore, LAT1 is regarded as a promising molecular target of novel anti-cancer therapeutics. In this study, we established a syngeneic and orthotropic mouse model for melanoma to examine the anti-tumor effects of LAT1 inhibitor. B16F10 mouse melanoma cells were orthotopically injected into footpads of C57BL/6J mice. One week after the inoculation, intravenous injection of LAT1 inhibitor was started and continued once-daily for two weeks. The tumor size on footpads of LAT1 inhibitor-treated mice was significantly reduced compared to those of saline-treated control mice, demonstrating the anti-tumor effects of LAT1 inhibitor. Our syngeneic and orthotropic model will be useful to evaluate the therapeutic efficacy of LAT1 inhibitors for melanoma in the presence of intact immune system, and also to investigate its detailed mechanisms of action as anti-tumor therapeutics.
Novel query optimization and evaluation techniques (2003)

In this thesis, we present novel query optimization and execution techniques for both new and traditional applications. We show that if we are operating over streaming sources, it is more beneficial to employ a rate-based cost model for query optimization. With respect to query execution over multi-join queries the introduction of operators being able to accept more than two inputs allows us to maximize the output rate of the query. Multi-input operators are straightforward extensions of traditional binary operators and are more resilient to fluctuations of the execution environment. The streaming environments naturally raise the question of when to use adaptive execution frameworks and when to stay with the “optimize then execute” paradigm. As a first step toward answering these questions, we revisit the query optimization problem over relational, disk-resident data and address the issue of the quality of the plans the relational optimizer chooses with respect to the errors in the cardinality estimates in the cost model's inputs. Towards that end we introduce the concept of error-aware query optimization.
Electrophoretic analysis of the novel antigen for the gastrointestinal‐specific monoclonal antibody, A33 (1997)

The murine monoclonal antibody A33 (mAbA33) recognises a human cell membrane-associated antigen selectively expressed in epithelial cells of the lower gastrointestinal tract and > 90% of colonic cancers, but is not detected in a wide range of other normal tissues by immunohistochemical analysis. In phase I/II clinical triasl, mAbA33 has been shown to target advanced colon cancers and the humanized version is currently being evaluated in therapy studies. Although the mAbA33 has been well characterised by immunohistochemical and clinical studies, until recently, the target antigen has remained poorly defined. This was largely attributable to the antigenic determinant recognised by mAbA33 being dependent on the native spatial conformation of the A33 antigen which impeded its identification by conventional two-dimensional electrophoresis (2-DE) and immunoblot analysis. We have developed an immunoblot method, based on nonreducing/non-urea precast 2-DE gels, that has facilitated the purification of the detergent (0.3% Triton X-100) solubilised A33 antigen from the human colon cancer cell lines LIM1215 and SW1222. Under these 2-DE conditions, the A33 antigen electrophoreses with an apparent M(r) approximately 41000 and pI 5.0-6.0. Attempts to isolate the A33 antigen from 2-DE gels for direct structural analysis were unsuccessful, due to its co-electrophoresis with actin and cytokeratin proteins. However, using Western blot and biosensor detection the A33 antigen has been purified chromatographically and N-terminal sequence analysis was possible. Using polyclonal antibodies raised against a synthetic peptide corresponding to the N-terminal region of the A33 antigen we have used Western blot analysis to localise the molecule in our master 2-DE protein database for normal human colon crypts and several colon carcinoma cell lines (URL address: http:(/)/www.ludwig.edu.au). Under reducing 2-DE conditions, the A33 antigen electrophoresis as 6 differentially charged isoforms (pI 4.6-4.8) with a single molecular weight species at M(r) approximately 55000.
Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cells. (2001)

The effect of the tritepene, ursolic acid, on the proliferation of A431 human epidermoid carcinoma cells was studied. According to our investigations, ursolic acid is a potent inhibitor of A431 cell growth. Ursolic acid markedly reduced A431 cell growth in a time- and dose-dependent manner. We found a good correlation between the results of direct cell counting and the MTT test. During long periods of drug exposure, ursolic acid exhibited both cytotoxic and cytostatic activity. The effect was partially reversible on drug removal. The greatest cytotoxicity was observed both in the trypan blue test and in the MTT test at 50 mM. Investigations on tyrosine kinase inhibition were performed by biochemical and cellular assays on A431 cells. Ursolic acid inhibited tyrosine kinase activity of A431 cells in biochemical assay in a dose-dependent manner with an IC50 of 24 mM. In cellular assay, when A431 cells were pretreated with ursolic acid for 24, 48 and 168 hours at various concentrations (5, 10, 20, 30 and 50 mM), lower values of IC50 were measured: 6.8 microM for 24 hours, 5.2 mM for 48 hours and 1.4 mM for 168 hours. The results suggest that ursolic acid exerts an antiproliferative effect through the inhibition of tyrosine kinase enzymes.
Gated-Attention Readers for Text Comprehension (2017)

In this paper we study the problem of answering cloze-style questions over documents. Our model, the Gated-Attention (GA) Reader 1 , integrates a multi-hop architecture with a novel attention mechanism, which is based on multiplicative interactions between the query embedding and the intermediate states of a recurrent neural network document reader. This enables the reader to build query-specific representations of tokens in the document for accurate answer selection. The GA Reader obtains state-of-the-art results on three benchmarks for this task-the CNN & Daily Mail news stories and the Who Did What dataset. The effectiveness of multiplicative interaction is demonstrated by an ablation study, and by comparing to alternative compositional operators for implementing the gated-attention.
Charge Optimization Theory for Induced-Fit Ligands (2012)

The design of ligands with high affinity and specificity remains a fundamental challenge in understanding molecular recognition and developing therapeutic interventions. Charge optimization theory addresses this problem by determining ligand charge distributions that produce the most favorable electrostatic contribution to the binding free energy. The theory has been applied to the design of binding specificity as well. However, the formulations described only treat a rigid ligand-one that does not change conformation upon binding. Here, we extend the theory to treat induced-fit ligands for which the unbound ligand conformation may differ from the bound conformation. We develop a thermodynamic pathway analysis for binding contributions relevant to the theory, and we illustrate application of the theory using HIV-1 protease with our previously designed and validated subnanomolar inhibitor. Direct application of rigid charge optimization approaches to nonrigid cases leads to very favorable intramolecular electrostatic interactions that are physically unreasonable, and analysis shows the ligand charge distribution massively stabilizes the preconformed (bound) conformation over the unbound. After analyzing this case, we provide a treatment for the induced-fit ligand charge optimization problem that produces physically realistic results. The key factor is introducing the constraint that the free energy of the unbound ligand conformation be lower or equal to that of the preconformed ligand structure, which corresponds to the notion that the unbound structure is the ground unbound state. Results not only demonstrate the applicability of this methodology to discovering optimized charge distributions in an induced-fit model, but also provide some insights into the energetic consequences of ligand conformational change on binding. Specifically, the results show that, from an electrostatic perspective, induced-fit binding is not an adaptation designed to enhance binding affinity; at best, it can only achieve the same affinity as optimized rigid binding.
P3–291: Real–time image acquisition to measure the effects of modulating phosphorylation on the overall rate of tau axonal transport in individual neurons (2006)

Tau is a neuronal cytoskeletal protein, the most well characterised function of which is its binding to and stabilisation of microtubules, which serve as tracks for axonal transport in neurons. Abnormalities in tau have been linked to a number of neurodegenerative disorders including Alzheimer's disease (AD). In AD brain tau is the main constituent of neurofibrillary tangles, which are composed of paired helical filaments of insoluble tau. Tau in these inclusions is abnormally phosphorylated, although the mechanisms linking phosphorylation to the formation of aggregates remain unclear. Phosphorylation may induce aggregation by changing the physical properties of tau, or may mediate tangle formation through a change in other properties of tau such as its microtubule binding or axonal transport. To develop a method for the study of the axonal transport of tau in individual cultured neurons. To examine the effect of modulating tau phosphorylation on its axonal transport. cDNA constructs of enhanced green fluorescent protein (EGFP) tagged tau were transfected into primary cultures of rat cortical neurons and images of individual neurons were collected at different timepoints after transfection. The rate of transport of tau–EGFP was calculated by measuring the distance from the axon hilum to the front of EGFP fluorescence in individual neurons. We were able to track net anterograde axonal transport in individual live neurons over several hours in culture. The rate of tau transport was comparable both to that previously observed in vivo and in vitro. Metabolic inhibition using 2–deoxy–D–glucose and sodium azide inhibited transport of tau thus validating our experimental system. Treatment of neurons with agents affecting tau phosphorylation was found to modulate tau transport. We have developed and validated a novel method to determine the rate of axonal transport of tau in individual neurons in culture. This experimental system can be used to investigate the effects of modulators of tau phosphorylation on its transport.
Computerized lesion detection on breast ultrasound (2002)

We investigated the use of a radial gradient index (RGI) filtering technique to automatically detect lesions on breast ultrasound. After initial RGI filtering, a sensitivity of 87% at 0.76 false-positive detections per image was obtained on a database of 400 patients (757 images). Next, lesion candidates were segmented from the background by maximizing an average radial gradient (ARD) index for regions grown from the detected points. At an overlap of 0.4 with a radiologist lesion outline, 75% of the lesions were correctly detected. Subsequently, round robin analysis was used to assess the quality of the classification of lesion candidates into actual lesions and false-positives by a Bayesian neural network. The round robin analysis yielded an Az value of 0.84, and an overall performance by case of 94% sensitivity at 0.48 false-positives per image. Use of computerized analysis of breast sonograms may ultimately facilitate the use of sonography in breast cancer screening programs.
Bronchial fistulae in ARDS patients: management with an extracorporeal lung assist device (2008)

Patients with bronchial tree lesions feature, in particular, a high risk for developing bronchial fistulae after surgical repair when the clinical situation is complicated by acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mechanical ventilation is needed. The current authors hypothesised that extracorporeal carbon dioxide removal would significantly decrease inspiratory airway pressures, thus promoting the protection of surgical bronchial reconstruction. Four patients were studied after surgical reconstruction of bronchial fistulae in whom ALI/ARDS developed and mechanical ventilation with positive end-expiratory pressure was required. Gas exchange, tidal volumes, airway pressures, respiratory frequency, vasopressor and sedation requirements were analysed before and after initiation of a pumpless extracorporeal lung assist device (pECLA; NovaLung, Talheim, Germany). Initiation of pECLA treatment enabled a reduction of inspiratory plateau airway pressures from 32.4 to 28.6 cmH(2)O (3.2 to 2.8 kPa), effectively treated hypercapnia (from 73.6 to 53.4 mmHg (9.8 to 7.1 kPa)) and abolished respiratory acidosis (from pH 7.24 to 7.41). All patients survived and were discharged to rehabilitation clinics. In patients after surgical bronchial reconstruction that was complicated by acute lung injury/acute respiratory distress syndrome, use of pumpless extracorporeal carbon dioxide removal was safe and efficient. Initiation of a pumpless extracorporeal lung assist device enabled a less invasive ventilator management, which may have contributed to healing of surgical bronchial repair.
A Selection Rule for Hydrofluoroether Electrolyte Cosolvent: Establishing a Linear Free‐Energy Relationship in Lithium–Sulfur Batteries (2019)

Abstract Hydrofluoroethers (HFEs) have been adopted widely as electrolyte cosolvents for battery systems because of their unique low solvating behavior. The electrolyte is currently utilized in lithium‐ion, lithium–sulfur, lithium–air, and sodium‐ion batteries. By evaluating the relative solvating power of different HFEs with distinct structural features, and considering the shuttle factor displayed by electrolytes that employ HFE cosolvents, we have established the quantitative structure–activity relationship between the organic structure and the electrochemical performance of the HFEs. Moreover, we have established the linear free‐energy relationship between the structural properties of the electrolyte cosolvents and the polysulfide shuttle effect in lithium–sulfur batteries. These findings provide valuable mechanistic insight into the polysulfide shuttle effect in lithium–sulfur batteries, and are instructive when it comes to selecting the most suitable HFE electrolyte cosolvent for different battery systems.