gebhart/patrepeval huggingface dataset:
Promising SINEs in the Treatment of Pancreatic Cancer (2015)

Pancreatic cancer remains a deadly disease in urgent need of newer therapeutic modalities. Pancreatic tumors are very heterogeneous and carry alterations in many critical pathways (i.e. harboring a robust biological network) rendering the design of therapy against a single pathway unrealistic. The disease requires a broad form of therapy that can target the activation of multiple tumor suppressor proteins simultaneously. It has been consistently shown in pancreatic cancer biopsies that there is an over-expression of the nuclear exporter protein exportin 1 also known as Chromosome maintenance region 1. Nuclear exporter protein exportin 1 is recognized to export major nuclear residing tumor suppressor proteins causing their functional inactivation through their mislocalization to the cytoplasmic compartment. This makes exportin 1 an attractive therapeutic target in pancreatic cancer. Supporting this we have clearly demonstrated that targeted inhibition of exportin 1 by our specific inhibitors of nuclear export can restore the function of multiple tumor suppressor proteins leading the pancreatic cancer cell death and tumor inhibition in orthotopic models. Additionally, studies have demonstrated that specific inhibitors of nuclear export synergize with gemcitabine and nab-paclitaxel leading to enhanced pancreatic cancer growth inhibition, apoptosis, and disintegration of cancer stem cell mimicking spheroids. Collectively these studies have lead to a Phase Ib/II clinical evaluation of specific inhibitors of nuclear export with GEM and nab-paclitaxel in patients with metastatic pancreatic cancer (ClinicalTrials.gov Identifier: NCT02178436). In this mini-review we highlight the promising specific inhibitors of nuclear export in pancreatic cancer.
A high-speed confocal laser-scanning microscope based on acousto-optic deflectors and a digital micromirror device (2004)

Neuronal dendrites are known to possess active computational properties. An ideal method of investigating these properties would be to monitor the complete electrical and chemical behavior of a single cell; however, currently available recording techniques force a tradeoff between spatial and temporal resolution. The objective of this project is to develop a confocal microscope that can make multisite optical recordings of single neuron function in a living brain slice at a frame rate sufficient to measure neuronal events that occur on a 1 ms timescale. Specifically, we would like to measure membrane potential and calcium concentration changes using voltage and ion-sensitive fluorescent indicators at user-selected sites-of-interest (SOIs). To accomplish this, we use acousto-optic deflectors (AODs) as random-access beam positioners in the illumination path, along with a digital micromirror device (DMD) as an addressable spatial filter in the detection path. We have demonstrated that our device is capable of optical sectioning and therefore capable of imaging in light-scattering preparations such as brain slices. Furthermore, our system is capable of an aggregate frame rate of up to 25 kHz.
Fast distance-driven projection and truncation management for iterative cone-beam CT reconstruction (2009)

International audience
The Therapeutic Potential of Allosteric Ligands for Free Fatty Acid Sensitive GPCRs (2013)

G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention in recent times is that of GPCR ligands that bind to allosteric sites on the receptor distinct from the orthosteric site of the endogenous ligand. As therapeutics, allosteric ligands possess many theoretical advantages over their orthosteric counterparts, including more complex modes of action, improved safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge of identifying allosteric leads and their often flat or confusing SAR. The present review will consider the advantages and challenges associated with allosteric GPCR ligands, and examine how the particular properties of these ligands may be exploited to uncover the therapeutic potential for free fatty acid sensitive GPCRs.
Microglial PHOX and Mac‐1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha‐synuclein (2007)

alpha-Synuclein, a gene whose mutations, duplication, and triplication has been linked to autosomal dominant familial Parkinson's disease (fPD), appears to play a central role in the pathogenesis of sporadic PD (sPD) as well. Enhancement of neurodegeneration induced by mutant alpha-synuclein has been attributed to date largely to faster formation of alpha-synuclein aggregates in neurons. Recently, we reported that microglial activation enhances wild type (WT) alpha-synuclein-elicited dopaminergic neurodegeneration. In the present study, using a primary mesencephalic culture system, we tested whether mutated alpha-synuclein could activate microglia more powerfully than WT alpha-synuclein, thereby contributing to the accelerated neurodegeneration observed in fPD. The results showed that alpha-synuclein with the A30P or A53T mutations caused greater microglial activation than WT alpha-synuclein. Furthermore, the extent of microglial activation paralleled the degree of dopaminergic neurotoxicity induced by WT and mutant alpha-synuclein. Mutant alpha-synuclein also induced greater production of reactive oxygen species than WT alpha-synuclein by NADPH oxidase (PHOX), and PHOX activation was linked to direct activation of macrophage antigen-1 (Mac-1) receptor, rather than alpha-synuclein internalization via scavenger receptors. These results have, for the first time, demonstrated that microglia are also critical in enhanced neurotoxicity induced by mutant alpha-synuclein.
Abstract 3020: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development (2018)

Abstract KRAS and EGFR have been shown to function as essential mediators of pancreatic cancer development. In addition, KRAS and EGFR have been separately shown to interact with and perturb the function of Argonaute 2 (AGO2), a key mediator of RNA-mediated gene silencing. Here, we employed a genetically engineered mouse model of pancreatic cancer to define the effects of conditional loss of AGO2 in KRASG12D driven pancreatic cancer. Genetic ablation of AGO2 does not interfere with development of the normal pancreas or KRASG12D driven early precursor pancreatic intraepithelial (PanIN) lesions. However, AGO2 loss prevents progression from early to late PanIN lesions, development of pancreatic ductal adenocarcinoma (PDAC), and metastatic progression. This results in a dramatic increase in survival of KRASG12D mutant mice deficient in AGO2 expression. In both mouse and human pancreatic tissues, increased AGO2 expression at the plasma membrane is associated with PDAC progression. Mechanistically, within early precursor PanIN lesions, loss of AGO2 elevates phospho-EGFR levels and activates wild-type RAS, antagonizing KRASG12D activation and PDAC development. Furthermore, we observe that phosphorylation of AGO2Y393 by EGFR disrupts the interaction of wild-type RAS with AGO2, but does not affect the interaction of mutant KRAS with AGO2. Taken together, our study supports a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR and wild-type RAS signaling, and an AGO2-dependent phase wherein the KRAS-AGO2 interaction is critical to the progression from PanIN to PDAC. A recent study by Phillip Sharp and Tyler Jacks describes a requirement for the oncogenic KRAS-AGO2 interaction in the development of a transplant mouse model of plasmablastic lymphoma, and together these studies substantiate the role of the interaction in KRAS oncogenesis. Citation Format: Sunita Shankar, Jean Tien, Ronald F. Siebenaler, Vijaya L. Dommeti, Sylvia Zelenka-Wang, Kristin M. Juckette, Alice Xu, Malay Mody, Andrew Goodrum, Grace Tsaloff, Ingrid J. Apel, Lisha Wang, Javed Siddiqui, Jiaqi Shi, Chandan Kumar-Sinha, Arul Chinnaiyan. An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3020.
Multimode Fabry–Perot Interferometer Probe Based on Vernier Effect for Enhanced Temperature Sensing (2019)

New miniaturized sensors for biological and medical applications must be adapted to the measuring environments and they should provide a high measurement resolution to sense small changes. The Vernier effect is an effective way of magnifying the sensitivity of a device, allowing for higher resolution sensing. We applied this concept to the development of a small-size optical fiber Fabry⁻Perot interferometer probe that presents more than 60-fold higher sensitivity to temperature than the normal Fabry⁻Perot interferometer without the Vernier effect. This enables the sensor to reach higher temperature resolutions. The silica Fabry⁻Perot interferometer is created by focused ion beam milling of the end of a tapered multimode fiber. Multiple Fabry⁻Perot interferometers with shifted frequencies are generated in the cavity due to the presence of multiple modes. The reflection spectrum shows two main components in the Fast Fourier transform that give rise to the Vernier effect. The superposition of these components presents an enhancement of sensitivity to temperature. The same effect is also obtained by monitoring the reflection spectrum node without any filtering. A temperature sensitivity of -654 pm/°C was obtained between 30 °C and 120 °C, with an experimental resolution of 0.14 °C. Stability measurements are also reported.
Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension (2018)

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment <i>in vitro</i> lipolysis model. Correlation of drug log<i>P</i> or solubility in SNEDDS with drug solubilization during <i>in vitro</i> lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, <i>w</i>/<i>w</i>) and Kolliphor RH40, with ethanol at 10% (<i>w</i>/<i>w</i>) were used. SNEDDS were named F65, F55 and F20 (numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS (F0) were also analyzed. While the ranking order of drug solubilization was F65=F55=F20>F0 for CAR; F65=F55>F20>F0 for CIN and F65=F55=F20>F0 for R3040 - with higher CAR solubilization than for R3040 and CIN - the ranking of <i>S</i> <sub>eq</sub> of CAR, CIN and R3040 in SNEDDS was F65<F55<F20, F65=F55>F20 and F65>F55>F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high <i>S</i> <sub>eq</sub> in SNEDDS did not reflect high drug solubilization. As CAR (log<i>P</i> 3.8) showed higher solubilization than CIN (log<i>P</i> 5.8) and R3040 (log<i>P</i> 10.4), a correlation between drug log<i>P</i> and drug solubilization was observed.
Figure S5 from Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer (2023)

&lt;p&gt;FKBP7 silencing effect in non-tumorous cells&lt;/p&gt;
Can Associative Polymers Reduce the Residual Oil Saturation? (2016)

Abstract The oil recovery potential of acrylamide-based, associative thickening polymers has recently been evaluated in a coreflood study of our department. Associative polymers are anionic, water-soluble copolymers modified with varying degress of pendant hydrophobic groups. By intermolecular interactions of these hydrophobic moieties a fully reversible network of polymer coils can be formed. The oil recovery efficiency of a series of copolymers based on acrylamide, 2-acrylamidopropane sulfonic acid (ATBS) in combination with a hydrophobic comonomer has been determined in linear coreflood experiments at a temperature of 60°C. Synthetic sea water was used as brine and Bentheimer sandstone as core material. The evaluated polymers differed in molecular weight and associative groups' content. While anionic polyacrylamide (APAM) shows very similar resistance factors (RF) in coreflood experiments with and without oil, a significantly reduced RF in the presence of oil has been found for the associative polymers. The magnitude of this decrease in resistance factor was dependent on the specific type of associative polymer. The effect can be ascribed to the weakend intermolecular interaction of the hydrophobic groups in the associative polymers in the presence of oil. Even though the RF value is reduced in the presence of oil, it still remains higher than that of regular APAM. At low flow rates representing reservoir conditions a high resistance factor was observed and oil production was improved. This observation can be explained by an increase of the capillary number caused by the high RF of the polymer drive. A good correlation between oil production and capillary number was established. Permeability reduction effects explained the high mobility reduction observed with the associative polymers, as the bulk viscosity data did not correlate with the in-situ flow properties of the polymers in porous media.
Integrated network analysis identifies nitric oxide response networks and dihydroxyacid dehydratase as a crucial target in Escherichia coli (2007)

Nitric oxide (NO) is used by mammalian immune systems to counter microbial invasions and is produced by bacteria during denitrification. As a defense, microorganisms possess a complex network to cope with NO. Here we report a combined transcriptomic, chemical, and phenotypic approach to identify direct NO targets and construct the biochemical response network. In particular, network component analysis was used to identify transcription factors that are perturbed by NO. Such information was screened with potential NO reaction mechanisms and phenotypic data from genetic knockouts to identify active chemistry and direct NO targets in Escherichia coli. This approach identified the comprehensive E. coli NO response network and evinced that NO halts bacterial growth via inhibition of the branched-chain amino acid biosynthesis enzyme dihydroxyacid dehydratase. Because mammals do not synthesize branched-chain amino acids, inhibition of dihydroxyacid dehydratase may have served to foster the role of NO in the immune arsenal.
Vibroarthography of the Knee Joint: A Comprehensive Gui-Based Analysis of Soft Tissue Damage (2013)

Introduction The low-cost, no-harm conditions associated with vibroarthography, the study of listening to the vibrations and sound patterns of interaction at the human joints, has made this method a promising tool for diagnosing joint pathologies. This current study focuses on the knee joint and aims to synchronize computational models with vibroarthographic signals via a comprehensive graphical user interface (GUI) to find correlations between kinematics, vibration signals, and joint pathologies. This GUI is the first of its kind to synchronize computational models with vibroarthographic signals and gives researchers a new advantage of analyzing kinematics, vibration signals, and pathologies simultaneously in an easy-to-use software environment. Methods The GUI (Figure 1) has the option to view live or previously captured fluoroscopic videos, the corresponding computational model, and/or the pre- or post-processed vibration signals. Having more than one signal axes available allows for comparison of different filtering techniques to the same signal, or comparison of signals coming from different sensor placements (ex: medial vs. lateral femoral condyle). Using computational models derived using fluoroscopic data synchronized with the vibration signals, the areas of contact between articulating surfaces can be mapped for the in vivo signal (figure 2). This new method gives the opportunity to find correlations between the different sensor signals and contact maps with the diagnosis and cartilage degeneration map, provided by a surgeon, during arthroscopy or TKA implantation (figure 3). Results Using previously captured data and newly acquired data for subjects from research studies, several different knee pathologies have been analyzed. The signals were listened to audibly after being processed to add a qualitative side. Sounds coming from knees with pathologies revealed noticeable differences compared to the healthy subjects, and the quantitative analysis further supported our hypothesis (>96% accuracy classification patella arthritic subjects vs. healthy). Discussion Ideally, transitioning towards real-time kinematic tracking with signal acquisition allows for diagnostic screening tools of the knee joint that will provide feedback of cartilage damage maps as well as potential meniscal or ligament injuries. The method used in this study is multi-faceted in that it allows the subject to perform various daily weight or non-weight bearing activities at his/her own speed which makes it easier to use than if the subject had to be in a very controlled environment.
Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm (2019)

Abdominal aortic aneurysm (AAA) is considered to be a potent life-threatening disorder in elderly individuals. Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. Recent advances in molecular biology have led to the identification of several important molecules, including microRNA and transcription factor, in the process of AAA formation. Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. Nucleic acid drugs can bind to target factors, mRNA, microRNA, and transcription factors in a sequence-specific fashion, resulting in a loss of function of the target molecule at the transcriptional or posttranscriptional level. Of note, inhibition of a transcription factor using a decoy strategy effectively suppresses experimental AAA formation, by regulating the expression of several genes associated with the disease progression. This review focuses on recent advances in molecular therapy of using nucleic acid drugs to treat AAA.
The Effect of Multilayer Patterns on Temperature Uniformity during Rapid Thermal Processing (1996)

This work aims to systematically gain an understanding of the effects of multilayer patterns on wafer temperature uniformity during rapid thermal processing (RTP) and to explore possible solutions to the problem. The radiative properties of patterned wafers are predicted using electromagnetic multilayer theory, including a model for the temperature‐dependent optical constants of silicon for wavelengths greater than 0.4 μm. The model for predicting radiative properties is coupled to a finite element‐based reactor transport model to predict steady‐state and transient wafer temperature distributions. A generic two‐dimensional axisymmetric single‐side illumination RTP system is used as a test bed to explore pattern effects. Realistic examples of shallow junction annealing and titanium silicidation are simulated. Results show that pattern effects are an important consideration for rapid thermal processes and that wafer processing, front and back side illumination, and reactor design all have significant effects on pattern‐induced temperature nonuniformity.
Novel Areas for Modeling and Simulation in the Automotive Industry: Prediction of Energy Consumption in Electric Vehicles (2011)

The introduction of battery electric vehicles (BEV) faces many challenges. For example, limited driving range, long charging time and sparse availability of charging stations lead to range anxiety for many prospective owners. There is a need for vehicle features that help BEV owners plan routes that avoid being stranded due to an empty battery. The key to these tools is the estimation of future energy consumption along different routes and under different driving conditions. How can this be done before sufficient statistical data is accumulated? Even when such vehicles are available it may not be possible to collect sufficient data to get meaningful statistics. This presentation describes a novel approach based on the integration of traffic simulation and propulsion modeling to predict BEV energy consumption.
Resampling-Based Empirical Bayes Multiple Testing Procedures for Controlling Generalized Tail Probability and Expected Value Error Rates: (2007)

This article proposes resampling-based empirical Bayes multiple testing procedures for controlling a broad class of Type I error rates, defined as generalized tail probability (gTP) error rates, gTP(q,g) = Pr(g(Vn,Sn) &gt; q), and generalized expected value (gEV) error rates, gEV(g) = [g(Vn,Sn)], for arbitrary functions g(Vn,Sn) of the numbers of false positives Vn and true positives Sn. Of particular interest are error rates based on the proportion g(Vn,Sn) = Vn/(Vn + Sn) of Type I errors among the rejected hypotheses, such as the false discovery rate (FDR), FDR = [Vn/(Vn + Sn)]. The proposed procedures offer several advantages over existing methods. They provide Type I error control for general data generating distributions, with arbitrary dependence structures among variables. Gains in power are achieved by deriving rejection regions based on guessed sets of true null hypotheses and null test statistics randomly sampled from joint distributions that account for the dependence structure of the data. The Type I error and power properties of an FDR-controlling version of the resampling-based empirical Bayes approach are investigated and compared to those of widely-used FDR-controlling linear step-up procedures in a simulation study. The Type I error and power trade-off achieved by the empirical Bayes procedures under a variety of testing scenarios allows this approach to be competitive with or outperform the Storey and Tibshirani [2003] linear step-up procedure, as an alternative to the classical Benjamini and Hochberg [1995] procedure.
How Mobility Impacts the Performance of Inter-Cell Coordination in Cellular Data Networks (2014)

In this paper, we assess the performance of inter-cell coordination in the presence of mobility. This performance depends primarily on the resource allocation scheme. Indeed, a scheduling strategy which may seem efficient when users are static can lead to bad performance when users are mobile. Several scheduling policies are investigated. Their performance critically depends on their ability to predict users' mobility. The results are based on the analysis of flow-level traffic models.
The Penicillin-Binding Proteins of Caulobacter crescentus1 (1980)

The proteins that specifically bind penicillin G were studied with Caulobacter crescentus. This organism possessed at least 5 penicillin-binding proteins (PBPs): PBP 1A (132 K), PBP 1Bs (98 K), PBP 2 (77 K), PBP 3 (64 K), and PBP 4 (50 K). As expected from the unique morphology, the C. crescentus PBPs were different from those of other sources in molecular weight and localization: C. crescentus did not possess PBPs of low molecular weight. PBP 4 was found only in the outer membrane, while the other PBPs were present mostly in the inner membrane.