gebhart/patrepeval huggingface dataset:
Abstract 4851: Selective small molecule inhibition of anti-apoptotic MCL-1 (2012)

Abstract BCL-2 family proteins are key regulators of the mitochondrial apoptotic pathway in health and disease. Anti-apoptotic members such as BCL-2, BCL-XL, and MCL-1 have been implicated in the initiation, progression, and chemoresistance of human cancer. The anti-apoptotic BCL-2/BCL-XL groove that binds and sequesters pro-apoptotic BH3 death helices has been successfully targeted by small molecules and peptides. Such compounds induce tumor cell apoptosis and are being advanced in clinical trials as promising next-generation cancer therapeutics. Notably, selective antagonists such as ABT-737 are highly effective at inducing apoptosis in BCL-2/BCL-XL-dependent cancers, but are rendered inactive by overexpression of MCL-1, a formidable chemoresistance protein that lies outside the molecule's binding spectrum. By screening a library of Stabilized Alpha-Helix of BCL-2 domains (SAHBs), we previously discovered that the MCL-1 BH3 helix is itself a potent and exclusive MCL-1 inhibitor (Stewart et al., Nat Chem Biol, 2010). Here, we deployed this natural peptidic inhibitor of MCL-1 in a competitive binding screen to identify an MCL-1 inhibitor molecule (MIM) that displays exquisite selectivity in in vitro binding and functional assays. NMR analysis documented that MIM engages the canonical BH3-binding pocket of MCL-1. Importantly, MIM selectively triggers caspase 3/7 activation and apoptosis in a cancer cell line that is dependent on induced overexpression of MCL-1, but showed no activity in the isogenic cell line that is driven instead by overexpressed BCL-XL. Conversely, ABT-737 manifested activity in the BCL-XL-overexpressing cancer cells but had no effect on the corresponding MCL-1-dependent cells. Thus, we report the application of MCL-1 SAHB to identify a selective small molecule inhibitor of MCL-1 that exhibits pro-apoptotic activity in the specific context of MCL-1 dependence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4851. doi:1538-7445.AM2012-4851
Distributed Differential Privacy By Sampling (2017)

In this paper, we describe our approach to achieve distributed differential privacy by sampling alone. Our mechanism works in the semi-honest setting (honest-but-curious whereby aggregators attempt to peek at the data though follow the protocol). We show that the utility remains constant and does not degrade due to the variance as compared to the randomized response mechanism. In addition, we show smaller privacy leakage as compared to the randomized response mechanism.
Can web pages be classified using anonymized TCP/IP headers? (2015)

Web page classification is useful in many domains- including ad targeting, traffic modeling, and intrusion detection. In this paper, we investigate whether learning-based techniques can be used to classify web pages based only on anonymized TCP/IP headers of traffic generated when a web page is visited. We do this in three steps. First, we select informative TCP/IP features for a given downloaded web page, and study which of these remain stable over time and are also consistent across client browser platforms. Second, we use the selected features to evaluate four different labeling schemes and learning-based classification methods for web page classification. Lastly, we empirically study the effectiveness of the classification methods for real-world applications.
DeepFont (2015)

As font is one of the core design concepts, automatic font identification and similar font suggestion from an image or photo has been on the wish list of many designers. We study the Visual Font Recognition (VFR) problem [4] LFE, and advance the state-of-the-art remarkably by developing the DeepFont system. First of all, we build up the first available large-scale VFR dataset, named AdobeVFR, consisting of both labeled synthetic data and partially labeled real-world data. Next, to combat the domain mismatch between available training and testing data, we introduce a Convolutional Neural Network (CNN) decomposition approach, using a domain adaptation technique based on a Stacked Convolutional Auto-Encoder (SCAE) that exploits a large corpus of unlabeled real-world text images combined with synthetic data preprocessed in a specific way. Moreover, we study a novel learning-based model compression approach, in order to reduce the DeepFont model size without sacrificing its performance. The DeepFont system achieves an accuracy of higher than 80% (top-5) on our collected dataset, and also produces a good font similarity measure for font selection and suggestion. We also achieve around 6 times compression of the model without any visible loss of recognition accuracy.
An evaluation of automated broncho-arterial ratios for reliable assessment of bronchiectasis (2008)

Bronchiectasis, the permanent dilatation of the airways, is frequently evaluated by computed tomography (CT) in order to determine disease progression and response to treatment. Normal airways have diameters of approximately the same size as their accompanying artery, and most scoring systems for quantifying bronchiectasis severity ask physicians to estimate the broncho-arterial ratio. However, the lack of standardization coupled with inter-observer variability limits diagnostic sensitivity and the ability to make reliable comparisons with follow-up CT studies. We have developed a Computer Aided Diagnosis method to detect airway disease by locating abnormal broncho-arterial ratios. Our approach is based on computing a tree model of the airways followed by automated measurements of broncho-arterial ratios at peripheral airway locations. The artery accompanying a given bronchus is automatically determined by correlation of its orientation and proximity to the airway, while the diameter measurements are based on the full-width half maximum method. This method was previously evaluated subjectively; in this work we quantitatively evaluate the airway and vessel measurements on 9 CT studies and compare the results with three independent readers. The automatically selected artery location was in agreement with the readers in 75.3% of the cases compared with 65.6% agreement of the readers with each other. The reader-computer variability in lumen diameters (7%) was slightly lower than that of the readers with respect to each other (9%), whereas the reader-computer variability in artery diameter (18%) was twice that of the readers (8%), but still acceptable for detecting disease. We conclude that the automatic system has comparable accuracy to that of readers, while providing greater speed and consistency.
Opportunities and Resistance to Signal-targeted Therapies in Pancreatic Cancer: What Can We Learn from Proteomic Studies? (2018)

In metastatic pancreatic cancer patients non eligible to surgery, signal-targeted therapies so far failed to show a significant amelioration of survival. These therapeutic options were tested in Phase II/III clinical trials mostly in combination with the reference treatment Gemcitabine. These innovative therapies aim at annihilating the oncogene dependency; they also aim at renormalizing the tumoral stroma to allow immune cell function or re-vascularisation. Transcriptomics and genomics large scale analysis show the great heterogeneity of pancreatic cancers and failed to clearly delineate specific oncogene dependency besides oncogenic Kras. In this review, we will describe the most recent proteomic data in pancreatic tumors and its metastasis, which could help at identifying their major signalling dependencies, as well as explain why they are intrinsically resistant to signal-targeted therapies. We will also discuss why PI3K signalling, as a paradigm of pro-tumorigenic cell signalling and of tumoral adaptative resistance to drugs, is a relevant target in this context.
Nuclease-Resistant DNA <i>via</i> High-Density Packing in Polymeric Micellar Nanoparticle Coronas (2013)

Herein, we describe a polymeric micellar nanoparticle capable of rendering nucleic acids resistant to nuclease digestion. This approach relies on utilizing DNA as the polar headgroup of a DNA-polymer amphiphile in order to assemble well-defined, discrete nanoparticles. Dense packing of DNA in the micelle corona allows for hybridization of complementary oligonucleotides while prohibiting enzymatic degradation. We demonstrate the preparation, purification, and characterization of the nanoparticles, then describe their resistance to treatment with endo- and exonucleases including snake-venom phosphodiesterase (SVP), a common, general DNA digestion enzyme.
Synergism between 9-deazainosine and DL-alpha-difluoromethylornithine in treatment of experimental African trypanosomiasis (1987)

Kinetoplastid hemoflagellates are sensitive to growth inhibition by various purine analogs. In this study the activities of 9-deazainosine (9-DINO), formycin B, and sinefungin were compared in experimental murine Trypanosoma brucei subsp. brucei infections, both singly and in combination with the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO, eflornithine). Used singly, all of the purine analogs were able to suppress an acute T. brucei subsp. brucei infection. 9-DINO and formycin B were the most active. None of the purine analogs was curative when used singly against a strain causing chronic central nervous system infection. 9-DINO was highly effective when used in combination with DFMO in curing this central nervous system infection and another more stringent experimental infection. Neither sinefungin nor formycin B was active in combination with DFMO in curing the central nervous system experimental infection. 9-DINO was metabolized to phosphorylated derivatives of 9-deazaadenosine and 9-deazaguanosine by bloodstream trypomastigotes, but not by murine erythrocyte suspensions or kidney or liver homogenates--a potential rationale for the selectivity of the analog. These studies indicate that 9-DINO is a potent, nontoxic purine analog which, in combination with DFMO, is capable of late-stage cures of African trypanosomiasis.
Programmable hydraulic resistor for microfluidic chips using electrogate arrays (2019)

Flow rates play an important role in microfluidic devices because they affect the transport of chemicals and determine where and when (bio)chemical reactions occur in these devices. Flow rates can conveniently be determined using external peripherals in active microfluidics. However, setting specific flow rates in passive microfluidics is a significant challenge because they are encoded on a design and fabrication level, leaving little freedom to users for adjusting flow rates for specific applications. Here, we present a programmable hydraulic resistor where an array of "electrogates" routes an incoming liquid through a set of resistors to modulate flow rates in microfluidic chips post-fabrication. This approach combines a battery-powered peripheral device with passive capillary-driven microfluidic chips for advanced flow rate control and measurement. We specifically show a programmable hydraulic resistor composed of 7 parallel resistors and 14 electrogates. A peripheral and smartphone application allow a user to activate selected electrogates and resistors, providing 127 (2<sup>7</sup>-1) flow resistance combinations with values spanning on a 500 fold range. The electrogates feature a capillary pinning site (i.e. trench across the flow path) to stop a solution and an electrode, which can be activated in a few ms using a 3 V bias to resume flow based on electrowetting. The hydraulic resistor and microfluidic chip shown here enable flow rates from ~0.09 nL.s<sup>-1</sup> up to ~5.66 nL.s<sup>-1</sup> with the resistor occupying a footprint of only 15.8 mm<sup>2</sup> on a 1 × 2 cm<sup>2</sup> microfluidic chip fabricated in silicon. We illustrate how a programmable hydraulic resistor can be used to set flow rate conditions for laminar co-flow of 2 liquids and the enzymatic conversion of a substrate by stationary enzymes (alkaline phosphatase) downstream of the programmable hydraulic resistor.
Control of Grafting Density and Distribution in Graft Polymers by Living Ring-Opening Metathesis Copolymerization (2017)

Control over polymer sequence and architecture is crucial to both understanding structure-property relationships and designing functional materials. In pursuit of these goals, we developed a new synthetic approach that enables facile manipulation of the density and distribution of grafts in polymers via living ring-opening metathesis polymerization (ROMP). Discrete endo,exo-norbornenyl dialkylesters (dimethyl DME, diethyl DEE, di-n-butyl DBE) were strategically designed to copolymerize with a norbornene-functionalized polystyrene (PS), polylactide (PLA), or polydimethylsiloxane (PDMS) macromonomer mediated by the third-generation metathesis catalyst (G3). The small-molecule diesters act as diluents that increase the average distance between grafted side chains, generating polymers with variable grafting density. The grafting density (number of side chains/number of norbornene backbone repeats) could be straightforwardly controlled by the macromonomer/diluent feed ratio. To gain insight into the copolymer sequence and architecture, self-propagation and cross-propagation rate constants were determined according to a terminal copolymerization model. These kinetic analyses suggest that copolymerizing a macromonomer/diluent pair with evenly matched self-propagation rate constants favors randomly distributed side chains. As the disparity between macromonomer and diluent homopolymerization rates increases, the reactivity ratios depart from unity, leading to an increase in gradient tendency. To demonstrate the effectiveness of our method, an array of monodisperse polymers (PLA<sup>x</sup>-ran-DME<sup>1-x</sup>)<sub>n</sub> bearing variable grafting densities (x = 1.0, 0.75, 0.5, 0.25) and total backbone degrees of polymerization (n = 167, 133, 100, 67, 33) were synthesized. The approach disclosed in this work therefore constitutes a powerful strategy for the synthesis of polymers spanning the linear-to-bottlebrush regimes with controlled grafting density and side chain distribution, molecular attributes that dictate micro- and macroscopic properties.
Microcomputer-based system for control of applied uniaxial stress and magnetic field (1984)

A system is described which allows on-line control of uniaxial stress and magnetic field for the investigation of the magnetic properties of materials under stress. This has been of considerable importance in studies of the properties of samples of steel, in particular the investigation of ferromagnetic hysteresis and the magnetomechanical effect. As a result, exact algorithms for the demagnetization of samples and for obtaining the anhysteretic or ideal magnetization curve have been devised.
A 2 1/4-turn spiral antenna for catheter cardiac ablation (1999)

To investigate the delivery of microwave energy by a catheter positioned inside the heart for ablating small abnormal regions producing cardiac arrhythmias, a 2 1/4-turn spiral catheter-based microwave antenna applicator has been developed. The antenna consists of the center conductor with continuous insulating material extending from the coaxial feed cable formed into a spiral antenna. The insulator completely isolates the center conductor from tissue. Phantom experiments were performed on homogeneous tissue equivalent medium. The reflection coefficient of the antenna at different frequencies and for different spiral lengths, the time course and temperature profile of an ablation, and the dosimetry of power versus temperature, all indicate that the high-power heating patterns from this antenna are both wider and deeper than with the other microwave antenna systems and radio-frequency electrodes.
Mesoporous Silica from Lyotropic Liquid Crystal Polymer Templates (1998)

Amphiphilic block copolymer templates in sol-gel processes yield bicontinuous silicates with distorted hexagonal symmetry (see, for example, the transmission electron migrograph depicted on the right). The long Bragg distance of 8-13 nm combined with the high mechanical and thermal stability suggests some promising prospects for chemistry and materials science.
Liquid crystal films as on-demand, variable thickness (50–5000 nm) targets for intense lasers (2014)

We have developed a new type of target for intense laser-matter experiments that offers significant advantages over those currently in use. The targets consist of a liquid crystal film freely suspended within a metal frame. They can be formed rapidly on-demand with thicknesses ranging from nanometers to micrometers, where the particular value is determined by the liquid crystal temperature and initial volume as well as by the frame geometry. The liquid crystal used for this work, 8CB (4′-octyl-4-cyanobiphenyl), has a vapor pressure below 10−6 Torr, so films made at atmospheric pressure maintain their initial thickness after pumping to high vacuum. Additionally, the volume per film is such that each target costs significantly less than one cent to produce. The mechanism of film formation and relevant physics of liquid crystals are described, as well as ion acceleration data from the first shots on liquid crystal film targets at the Ohio State University Scarlet laser facility.
Vehicle counting and classification algorithms for unattended ground sensors (2003)

Unattended ground sensor technology used for battlefield awareness and other wide area surveillance applications requires state-of-the-art algorithms to address the unprecedented challenges faced in detecting, classifying and tracking military combat vehicles. The performance of traditional acoustic sensor systems often degrades unacceptably against the dynamic and highly mobile multiple target environments in which today's forces must operate. In the present work, a target counting algorithm has been developed to solve problems attributed to unstable tracking performance by resolving track loss deficiencies inherent to closely spaced target environments. The algorithm provides a way to discriminate between vehicles as they pass through an acoustic trip-line formed by a sensor in a predetermined field of view (FOV). The proposed approach is realized through an adaptive beamforming algorithm that achieves enhanced directivity in a principal look direction by significantly reducing the effects of interferers outside the precise bearing of the steering direction. The classification algorithm described herein facilitates a minimal representation for features extracted from harmonically related structures characteristic to acoustic emissions from ground vehicles found in battlefield environments. The reduced feature space representation exploits an ordering for the principal narrowband components found in a vehicle's engine noise and has proven effective in solving fundamental problems associated with discriminating between vehicles in variable SNR environments. The performance of the algorithms is demonstrated using signature data collected during various acoustic sensor field test experiments.
Mitosis: Transparently Self-Replicating Page-Tables for Large-Memory\n Machines (2019)

Multi-socket machines with 1-100 TBs of physical memory are becoming\nprevalent. Applications running on multi-socket machines suffer non-uniform\nbandwidth and latency when accessing physical memory. Decades of research have\nfocused on data allocation and placement policies in NUMA settings, but there\nhave been no studies on the question of how to place page-tables amongst\nsockets. We make the case for explicit page-table allocation policies and show\nthat page-table placement is becoming crucial to overall performance. We\npropose Mitosis to mitigate NUMA effects on page-table walks by transparently\nreplicating and migrating page-tables across sockets without application\nchanges. This reduces the frequency of accesses to remote NUMA nodes when\nperforming page-table walks. Mitosis uses two components: (i) a mechanism to\nenable efficient page-table replication and migration; and (ii) policies for\nprocesses to efficiently manage and control page-table replication and\nmigration. We implement Mitosis in Linux and evaluate its benefits on real\nhardware. Mitosis improves performance for large-scale multi-socket workloads\nby up to 1.34x by replicating page-tables across sockets. Moreover, it improves\nperformance by up to 3.24x in cases when the OS migrates a process across\nsockets by enabling cross-socket page-table migration.\n
<i>Mycobacterium avium</i>subspecies<i>hominissuis</i>in Crohn’s disease: a case report (2015)

We have cultured Mycobacteria avium subspecies hominissuis (MAH) from the blood of a patient with Crohn's disease. The patient is a 21 year-old-female with a diagnosis of Crohn's disease for two years. She had been treated with corticosteroids and Humira for six months. A blood specimen was cultured in a specialized medium, and there was visible bacterial growth present in the liquid culture medium after eight weeks. PCR analysis of the bacterial growth and subsequent direct sequencing of the PCR amplicon confirmed the presence of MAH. The significance of this finding is discussed.
An OCTA Based Diagnosis System Based on a Comprehensive Local Features Analysis for Early Diabetic Retinopathy Detection (2018)

In this work, we propose a comprehensive diagnosis system for detecting early signs of diabetic retinopathy (DR). The proposed system is based on extracting features that are describing both shape and appearance of the retinal vascular system from optical coherence tomography angiography (OCTA) scans. First, two various OCTA plexuses are segmented, which are retinal superficial and deep plexuses, to extract the retinal blood vessels from the other background tissues. Then, the developed system calculates the blood vessels density, blood vessels caliber, and distance map of the foveal avascular zone (FAZ) from both two segmented OCTA plexuses. Also, the large blood vessels are extracted from the segmented superficial plexus to retrieve the skeleton of the blood vessels. The skeleton of the large blood vessels is used to calculate bifurcation, crossover, and branch points. Finally, the extracted four features that are capturing shape and appearance of the segmented vessels and FAZ, which are blood vessels density, blood vessel caliber, the width of the FAZ, and different types of vascular bifurcation points are used to diagnosis the OCTA images by using two-stage random forest (RF) classifier. To measure the performance of the proposed system, 133 OCTA scans for different patients are used for training and testing based on k-fold cross-validation technique. The performance of the proposed system is measured by using five various metrics. A promising average result of overall accuracy (ACC) of 97% is obtained that can differentiate normal from mild DR cases.