gebhart/patrepeval huggingface dataset:
Abstract LB-10: Rational design of small molecules targeting the Ras GEF, SOS1 (2014)

Abstract Ras GTPases regulate multiple intracellular signaling processes involved in gene expression, cell proliferation, and cell survival. Driver mutations of Ras signaling components including K,N,H-Ras, EGFR, PDGFR, Raf, PI3K, and Akt have been found in many types of human cancers. The activation of Ras is catalyzed by guanine-nucleotide exchange factors (GEFs), which stimulate the exchange of GDP for GTP. SOS1 is a major RasGEF that transduces receptor tyrosine kinase signals to Ras and associated ERK/Akt pathways. SOS1 gain-of-function mutations have been found in Noonan syndrome patients. In addition, SOS1 has been shown to be differentially expressed in prostate and breast cancer cells, and is involved in malignancies dependent upon aberrant Ras signaling. In the current studies, we undertake a structure-based virtual screening approach, coupled with biochemical and cell biological validations, to identify lead chemical inhibitors targeting the Ras catalytic domain of SOS1. From a 118,500 compound subset of the NCI/DTP Open Chemical Repository, 135 showed optimal docking energy to a grid of the SOS1 catalytic site from which 36 were selected for experimental screening by a guanine nucleotide exchange assay, i.e. FL-GDP dissociation of Ras under the catalysis of SOS1. Two compounds were confirmed as true hits (NSC-674954 and NSC-658497), of which NSC-658497 displayed micromolar IC50s in both inhibiting FL-GDP dissociation (IC50 - 22.2 µM) from Ras and TR-GTP loading (IC50 - 40.8 µM) of Ras catalyzed by Sos1. In addition, NSC-658497 displayed a target binding Kd of ∼7.0 µM as assayed by microscale thermophoresis, along with dose-dependently disrupting the SOS1 interaction with Ras as assayed by a GST-Ras pull-down analysis. Mutagenesis studies mapped NSC-658497 action site to the catalytic site in SOS1, involving specifically residues I825, T828, T829, and Y912. SAR analysis revealed that NSC-658497 elicits its inhibitory effect on SOS1 through a benzopyran and nitrophenyl moiety. In fibroblast cells, NSC-658497 showed dose-dependent efficacy in inhibiting EGF-stimulated Ras and ERK/AKT activities. Furthermore, NSC-658497 dose-dependently inhibited NIH/3T3, MEF, and MIA-PaCa-2 pancreatic cancer cell proliferation in conjunction with their respective downstream Ras-dependent ERK/AKT activities. Thus, we have identified a class of lead chemical inhibitors targeting SOS1 that can serve as useful tools for studying SOS1 mediated oncogenesis and as hits for further development of future cancer therapeutics. Citation Format: Chris Evelyn, Xin Duan, Jacek Biesiada, William Seibel, Jaroslaw Meller, Yi Zheng. Rational design of small molecules targeting the Ras GEF, SOS1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-10. doi:10.1158/1538-7445.AM2014-LB-10
Data from Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here, we identify cancer-specific promoter DNA methylation of &lt;i&gt;BNC1&lt;/i&gt; and &lt;i&gt;ADAMTS1&lt;/i&gt; as a promising biomarker detection strategy meriting investigation in pancreatic cancer.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of eight promising genes, we focused our studies on &lt;i&gt;BNC1&lt;/i&gt; and &lt;i&gt;ADAMTS1&lt;/i&gt; for further downstream analysis, including methylation and expression. We used a nanoparticle-enabled methylation on beads (MOB) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We identified two novel genes, &lt;i&gt;BNC1&lt;/i&gt; (92%) and &lt;i&gt;ADAMTS1&lt;/i&gt; (68%), that showed a high frequency of methylation in pancreatic cancers (&lt;i&gt;n&lt;/i&gt; = 143), up to 100% in PanIN-3 and 97% in stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (&lt;i&gt;n&lt;/i&gt; = 42) from patients with pancreatic cancer, with a sensitivity for &lt;i&gt;BNC1&lt;/i&gt; of 79% [95% confidence interval (CI), 66%–91%] and for &lt;i&gt;ADAMTS1&lt;/i&gt; of 48% (95% CI, 33%–63%), whereas specificity was 89% for &lt;i&gt;BNC1&lt;/i&gt; (95% CI, 76%–100%) and 92% for &lt;i&gt;ADAMTS1&lt;/i&gt; (95% CI, 82%–100%). Overall sensitivity using both markers is 81% (95% CI, 69%–93%) and specificity is 85% (95% CI, 71%–99%).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Promoter DNA methylation of &lt;i&gt;BNC1&lt;/i&gt; and &lt;i&gt;ADAMTS1&lt;/i&gt; is a potential biomarker to detect early-stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early detection of pancreatic cancer and has the potential to improve mortality from this disease. &lt;i&gt;Clin Cancer Res; 19(23); 6544–55. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Adhesion Between Similar and Dissimilar Thin-Walled Micro-Structures (2009)

A novel boundary condition is introduced to calculate the adhesion of similar and dissimilar thin-walled microstructures. By casting the energy release rate for debonding in terms of a discontinuity in bending curvature at the contact boundary, it is possible to study such systems using conventional plate theory. This result is of particular importance in modeling the aggregation of heterogeneous carbon-nano-tubes or spherical cells, where the contacting microstructures have a different radius and/or bending stiffness.
Phase control of α- and κ-Ga2O3 epitaxial growth on LiNbO3 and LiTaO3 substrates using α-Fe2O3 buffer layers (2020)

LiNbO3 and LiTaO3 substrates are used in wide-bandwidth applications such as surface acoustic wave filter and show structural similarity to α-Ga2O3. In this study, we demonstrated the phase control of Ga2O3 epitaxial thin films, grown by mist chemical vapor deposition, on the (0001) planes of LiNbO3 and LiTaO3 substrates using α-Fe2O3 buffer layers. κ-Ga2O3 thin films were grown epitaxially on bare LiNbO3 and LiTaO3 substrates. Conversely, the insertion of the α-Fe2O3 buffer layer led to the preferential growth of the α-Ga2O3 epitaxial thin films. X-ray diffraction (XRD) φ-scan results revealed that the α-Ga2O3 thin films were grown along the same in-plane direction as that of the substrates. Besides, the XRD φ-scan results indicated that twin-free α-Ga2O3 was grown on the LiNbO3 and LiTaO3 substrates with the α-Fe2O3 buffer layers. The x-ray rocking curve scans of the asymmetric plane of α-Ga2O3 showed that the full width at half maximum values of α-Ga2O3 on the LiNbO3 and LiTaO3 substrates with the buffer layers were smaller than that of the c-plane α-Al2O3 substrate with and without the buffer layer. In addition, we grew the (11-20) and (1-100) planes of the α-Ga2O3 epitaxial thin films on the (11-20) and (1-100) planes of LiNbO3 substrates with the α-Fe2O3 buffer layer, respectively. This study showed that LiTaO3 and LiNbO3 are promising substrates for the epitaxial growth of α-Ga2O3 and κ-Ga2O3.
Environmentally Sustainable and Ecosafe Polysaccharide-Based Materials for Water Nano-Treatment: An Eco-Design Study (2018)

Nanoremediation, which is the use of nanoparticles and nanomaterials for environmental remediation, is widely explored and proposed for preservation of ecosystems that suffer from the increase in human population, pollution, and urbanization. We herein report a critical analysis of nanotechnologies for water remediation by assessing their sustainability in terms of efficient removal of pollutants, appropriate methods for monitoring their effectiveness, and protocols for the evaluation of any potential environmental risks. Our purpose is to furnish fruitful guidelines for sustainable water management, able to promote nanoremediation also at European level. In this context, we describe new nanostructured polysaccharide-based materials obtained from renewable resources as alternative efficient and ecosafe solutions for water nano-treatment. We also provide eco-design indications to improve the sustainability of the production of these materials, based on life-cycle assessment methodology.
Agents other than taxanes in active development for the treatment of breast cancer (1998)

info:eu-repo/semantics/published
A Study of operational stability on performance for simplified volute pump (2018)

This research proposes a volute pump with a simple structure in which circular tubes are radially combined, and verified a pump performance and characteristics by numerical analysis and experiment. As a result, it was found that when the Coriolis force becomes dominant in the pipeline, the gas phase entered from the discharge port, and the performance of the pump decreases.
E-046 Length of stay in mechanical thrombectomy, and machine learning improvement of predictive analysis (2017)

<h3>Purpose</h3> Machine learning has recently been shown to increase the predictive power for the outcomes of hemorrhage and patient modified Rankin Scale(mRS) from pre-intervention data. Machine learning techniques have not been assessed for prediction of length of stay. Pre-procedural and post-procedural variables were also assessed to determine predictors of length of stay. <h3>Methods</h3> 600 consecutive patients evaluated with CT perfusion for stroke were retrospectively analyzed. Patients were included if thrombectomy was attempted and excluded if the pre-intervention dataset was incompletely documented, 158 patients were included in the study. We compiled a data set using previous randomized controlled trials and retrospective analysis to guide items selected for data collection. Using data available prior to intervention the data set was divided into training and testing sets via sampling with repletion with a sampling ratio of 0.9. Machine learning models including artificial neural network (ANN), support vector machine (SVM), and multivariate linear regression models were created to predict patient length of stay from pre-intervention data. T-test with Sidak multiple testing correction was used to compare models based on root mean squared error generated from model application to unseen data. To assess statistically significantly variables for length of stay, univariate analysis was performed. <h3>Results</h3> Length of of stay in this sample had a mean of 9.8±7.9 days. Median LOS was 8 days.In this patient population factors significantly associated with increased LOS were initial NIHSS, ASPECT score, hemorrhage, and infarct size, all with p&lt;0.05.Support vector machine models (RMSE 8.155±1.325) significantly outperformed linear regression, (8.764±1.094) with p=0.001 for RMSE, at prediction of length of stay. Neural network models on average performed significantly worse than either other model (RMSE 15.583±2.457). <h3>Conclusions</h3> Machine learning methods outperform multivariate logistic regression at the prediction of length of stay. Predictive analysis for patient length of stay could help hospital utilization and allow for more aggressive measures to prevent hospital acquired conditions. <h3>Disclosures</h3> <b>S. Arndt:</b> None. <b>G. Bennett:</b> None. <b>K. Wojcik:</b> None. <b>A. Albar:</b> None. <b>M. Alhasan:</b> None. <b>J. Ma:</b> None. <b>P. Gulotta:</b> None. <b>J. Milburn:</b> None.
Broadband Near Infrared Supercontinuum for Z-Scan Nonlinear Spectrometer (2017)

High-spectral-irradiance infrared supercontinuum with fundamental Gaussian spatial profile was generated in Krypton gases. We demonstrate its usefulness for Z-scan nonlinear spectroscopy in the 800-1600nm spectral range using GaAs and CS2.
Hybrid electrodialysis reverse osmosis system design and its optimization for treatment of highly saline brines (2014)

The demand is rising for desalination technologies to treat highly saline brines arising from hydraulic fracturing processes and inland desalination. Interest is growing in the use of electrical desalination technologies for this application. The hybridization of electrodialysis (ED) with reverse osmosis (RO) allows high salinities (beyond the range of RO alone) to be reached while avoiding the operation of ED with a low conductivity diluate stream. Such hybrid systems have been experimentally investigated for concentrates from brackish and seawater desalination. However, progress is required in the modelling and optimization of hybrid systems at higher concentrations. A novel hybrid arrangement of counterflow ED systems with reverse osmosis is presented to concentrate a saline feed at 120 ppt. The system is considered from the perspective of efficiency, membrane productivity and the levelised cost of water, with emphasis on the optimisation of current density. In contrast to brackish ED systems, membrane resistances are found to dominate diluate and concentrate resistances at high salinity. The current density found to minimise LCW (levelised cost of water) is significantly greater than the current density found to maximise efficiency, indicating the high current capital cost of ED per unit membrane area and poor membrane transport properties relative to RO. Finally, performance at high recoveries is found to be limited by high stream-to-stream concentration differences, increasing water transport via osmosis, decreasing efficiency and increasing the LCW.
Chemokine Receptors Expression and Migration Potential of Tumor-infiltrating and Peripheral-expanded Vγ9Vδ2 T Cells From Renal Cell Carcinoma Patients (2008)

We previously showed that Vdelta2 T cells infiltrate renal tumors and can be expanded as potent cytotoxic effectors from peripheral blood mononuclear cells of most renal cell carcinoma (RCC) patients, using a structural analog of nonconventional T-cell receptor gamma9delta2 ligand, bromohydrin pyrophosphate, and interleukin-2 (IL-2). In this study, we have further investigated the differentiation status and the migration potential of circulating and tumor-infiltrating Vgamma9Vdelta2 T lymphocytes from RCC patients. The repertoire of tumor-infiltrating and peripheral Vgamma9Vdelta2 T cells from RCC patients was characterized by a dominant CD27- CD45RA- subset. These effector memory Vgamma9Vdelta2 T cells were efficiently expanded using bromohydrin pyrophosphate combined with IL-15, but not IL-2. In addition, peripheral Vgamma9Vdelta2 T cells from RCC patients present a modified chemotactic pattern compared with donors. After ex vivo activation, peripheral expanded Vgamma9Vdelta2 T cells acquire low-migration capacities toward renal cells. Tumor-infiltrating Vgamma9Vdelta2 T cells migrated with higher efficiency toward primary renal tumor cells. The traffic toward tumor cells required the CXCL12/CXCR4 interaction. Altogether, these results outline that those Vgamma9Vdelta2 effectors exhibit differential migration capacities according to their localization, their differentiation status, and the tumor microenvironment parameters that may influence their use in immunotherapy.
The DNA sequence and comparative analysis of human chromosome 20 (2001)

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
Approximate Dynamic Programming for a Mean-field Game of Traffic Flow: Existence and Uniqueness (2023)

Highway vehicular traffic is an inherently multi-agent problem. Traffic jams can appear and disappear mysteriously. We develop a method for traffic flow control that is applied at the vehicular level via mean-field games. We begin this work with a microscopic model of vehicles subject to control input, disturbances, noise, and a speed limit. We formulate a discounted-cost infinite-horizon robust mean-field game on the vehicles, and obtain the associated dynamic programming (DP) PDE system. We then perform approximate dynamic programming (ADP) using these equations to obtain a sub-optimal control for the traffic density adaptively. The sub-optimal controls are subject to an ODE-PDE system. We show that the ADP ODE-PDE system has a unique weak solution in a suitable Hilbert space using semigroup and successive approximation methods. We additionally give a numerical simulation, and interpret the results.
Conservation of Hsp90 macromolecular complexes in Saccharomyces cerevisiae. (1994)

In higher eukaryotic cells, the Hsp90 chaperone protein is found in complexes with other proteins, in addition to the substrate protein. These other proteins include Hsp70, p60, and several peptidyl-prolyl cis-trans isomerases (immunophilins). We utilized affinity chromatography to investigate whether Hsp82, the Hsp90 of Saccharomyces cerevisiae, is found in similar complexes in that organism. Six histidine residues were fused to the N terminus of Hsp82 to yield a fusion protein (Hsp82FP) with affinity for a nickel-ion matrix. Hsp82FP was shown to have wild-type function. In addition, when mammalian substrates of Hsp90 (glucocorticoid receptor and p60v-src) were expressed in yeast cells, these proteins bound to the affinity matrix only when isolated from cells containing Hsp82FP. Yeast homologs of Hsp70 (in particular, members of the Ssa subfamily), p60 (Sti1), and a 45-kDa immunophilin homolog were also isolated in this manner, by virtue of their specific, stable association with Hsp82. Thus, Hsp90 functions as part of a highly conserved macromolecular complex in eukaryotes.
Brightness preserving dynamic fuzzy histogram equalization (2010)

This paper proposes a novel modification of the brightness preserving dynamic histogram equalization technique to improve its brightness preserving and contrast enhancement abilities while reducing its computational complexity. The modified technique, called Brightness Preserving Dynamic Fuzzy Histogram Equalization (BPDFHE), uses fuzzy statistics of digital images for their representation and processing. Representation and processing of images in the fuzzy domain enables the technique to handle the inexactness of gray level values in a better way, resulting in improved performance. Execution time is dependent on image size and nature of the histogram, however experimental results show it to be faster as compared to the techniques compared here. The performance analysis of the BPDFHE along with that for BPDHE has been given for comparative evaluation.
Challenges in Cell Fate Acquisition to Scid-Repopulating Activity from Hemogenic Endothelium of hiPSCs Derived from AML Patients Using Forced Transcription Factor Expression (2022)

The generation of human hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) represents a major goal in regenerative medicine and is believed would follow principles of early development. HSCs arise from a type of endothelial cell called a "hemogenic endothelium" (HE), and human HSCs are experimentally detected by transplantation into SCID or other immune-deficient mouse recipients, termed SCID-Repopulating Cells (SRC). Recently, SRCs were detected by forced expression of seven transcription factors (TF) (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, and SPI1) in hPSC-derived HE, suggesting these factors are deficient in hPSC differentiation to HEs required to generate HSCs. Here we derived PECAM-1-, Flk-1-, and VE-cadherin-positive endothelial cells that also lack CD45 expression (PFV<sup>CD45-</sup>) which are solely responsible for hematopoietic output from iPSC lines reprogrammed from AML patients. Using HEs derived from AML patient iPSCs devoid of somatic leukemic aberrations, we sought to generate putative SRCs by the forced expression of 7TFs to model autologous HSC transplantation. The expression of 7TFs in hPSC-derived HE cells from an enhanced hematopoietic progenitor capacity was present in vitro, but failed to acquire SRC activity in vivo. Our findings emphasize the benefits of forced TF expression, along with the continued challenges in developing HSCs for autologous-based therapies from hPSC sources.
Treatment and detection of tuberculosis, leprosy, and related diseases (2023)

Method for treatment of an infection in an animal or plant by an organism having a non-discriminating DNA polymerase. The organism is contacted with a therapeutically effective amount of a dideoxynucleoside or dideoxynucleotide in a pharmaceutically acceptable buffer. Such contact reduces the infection or a symptom of the infection in the animal or plant.
Finding shell company accounts using anomaly detection (2018)

Money laundering refers to activities pertaining to hiding the true income, evading taxes, or converting illegally earned money for normal use. These activities are often performed through shell companies that masquerade as real companies but where actual the purpose is to launder money. Shell companies are used in all the three phases of money laundering, namely, placement, layering, and integration, often simultaneously. In this paper, we aim to identify shell companies. We propose to use only bank transactions since that is easily available. In particular, we look at all incoming and outgoing transactions from a particular bank account along with its various attributes, and use anomaly detection techniques to identify the accounts that pertain to shell companies. Our aim is to create an initial list of potential shell company candidates which can be investigated by financial experts later. Due to lack of real data, we propose a banking transactions simulator (BTS) to simulate both honest as well as shell company transactions by studying a host of actual real-world fraud cases. We apply anomaly detection algorithms to detect candidate shell companies. Results indicate that we are able to identify the shell companies with a high degree of precision and recall.1
Containing Timing-Related Certification Cost in Automotive Systems Deploying Complex Hardware (2014)

Measurement-Based Probabilistic Timing Analysis (MBPTA) techniques simplify deriving tight and trustworthy WCET estimates for industrial-size programs running on complex processors. MBPTA poses some requirements on the timing behaviour of the hardware/software platform: execution times of end-to-end runs have to be independent and identically distributed (i.i.d.). Hardware and software solutions have been deployed to accomplish MBPTA requirements. The latter has achieved the i.i.d. properties running on some commercial off-the-shelf (COTS) processor designs. Unfortunately, software randomisation challenges functional verification needed for certification since it introduces indirections through pointers in the code. In this paper we propose a new approach to software randomisation able to contain its functional verification costs. Our approach performs software randomisation statically, as opposed to current dynamic approaches. We carefully review the requirements of the new approach and prove its feasibility.