gebhart/patrepeval huggingface dataset:
Abstract A42: Paracrine regulation of the pancreatic cancer epigenome (2015)

Abstract Development of pancreatic ductal adenocarcinoma (PDAC) follows an increasingly well-defined series of genetic events in the pancreatic epithelium. Less well understood are the steps orchestrating the exuberant desmoplasia that accompanies every case of PDAC. This accumulation of stromal components arises from and is maintained by the reciprocal interactions between genetically altered tumor cells and adjacent stroma. Pancreatic stellate cells (PSCs) are myofibroblast-like cells activated by tissue damage and implicated in wound healing. Recent work suggests that PSCs are key primary drivers of the desmoplastic reaction that characterizes the disease, possibly through their established secretory capacity. We wished to explore the paracrine effects of PSC secreted factors on gene expression in pancreatic cancer cells. To investigate the global gene expression changes induced by stromal factors, PDAC cell lines were grown in “a-stromal” or “stromal” conditions. The addition of structural and diffusible PSC-derived factors significantly altered expression of thousands of genes in the cancer genome, suggesting that these factors exert genome-wide effects on the epigenetic state to so broadly affect transcription level. Stromal inputs lead to broad hyperacetylation of histones in the PDAC epigenome, particularly on gene-activating lysines on histone tails. These epigenetic events coincided with induction of genes implicated in anabolic metabolism, the glycosylation pathway, and inflammation. The gene expression changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental cues characteristic of PDAC. As epigenome modification results in changes in gene expression through the functions of readers, we tested a small molecule inhibitor of a family of epigenetic readers for the capacity to inhibit gene expression changes downstream of stromal factors. Paracrine induction of pro-growth and inflammatory genes was inhibited by this small molecule, suggesting that acetyl-lysine readers serve as key transducers of stromal inputs to drive alterations in gene expression in pancreatic cancer cells. Inhibition of acetyl-lysine sensing reduced pancreatic tumor growth and associated inflammation in vivo, with significant reduction in expression of genes implicated in macromolecule biosynthesis and tumor-permissive immune regulation. This work supports further investigation of epigenetic modulators, in combination with targeted drugs or immunotherapeutic approaches, for the treatment of PDAC. Citation Format: Mara H. Sherman, Eric Collisson, Michael Downes, Ronald M. Evans. Paracrine regulation of the pancreatic cancer epigenome. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A42.
Survey of Culture, GoldenGate Assay, Universal Biosensor Assay, and 16S rRNA Gene Sequencing as Alternative Methods of Bacterial Pathogen Detection (2013)

Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay (ELISA)-based methods for finding virulence factors are standard methods for detecting bacterial pathogens in stools; however, with emerging molecular technologies, new methods have become available. The aim of this study was to compare four distinct detection technologies for the identification of pathogens in stools from children under 5 years of age in The Gambia, Mali, Kenya, and Bangladesh. The children were identified, using currently accepted clinical protocols, as either controls or cases with moderate to severe diarrhea. A total of 3,610 stool samples were tested by established clinical culture techniques: 3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.), 1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by sequencing of 16S rRNA genes. Each method detected different proportions of samples testing positive for each of seven enteric pathogens, enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas spp. The comparisons among detection methods included the frequency of positive stool samples and kappa values for making pairwise comparisons. Overall, the standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller proportions of the samples than either of the methods based on detection of the virulence genes from DNA in whole stools. The GoldenGate method revealed the greatest agreement with the other methods. The agreement among methods was higher in cases than in controls. The new molecular technologies have a high potential for highly sensitive identification of bacterial diarrheal pathogens.
A global approach to path planning for redundant manipulators (1995)

This paper presents a new approach to path planning for redundant manipulators. The path planning problem is posed as a finite time nonlinear control problem which can be solved by a Newton-Raphson type algorithm together with an exterior penalty function method. This technique is capable of handling various goal task definitions as well as incorporating both joint and task space constraints. The algorithm has shown promising results in planning joint path sequences to meet Cartesian goal planning and path following. In contrast to local approaches, this algorithm is less prone to problems such as singularities and local minima. Applications to planar 3R and 4R arms, cooperating 3R arms and a spatial 9 DOF arm are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mapping the interaction between the cytoplasmic domains of HIV‐1 viral protein U and human CD4 with NMR spectroscopy (2012)

Viral protein U (VpU) of HIV-1 plays an important role in downregulation of the main HIV-1 receptor CD4 from the surface of infected cells. Physical binding of VpU to newly synthesized CD4 in the endoplasmic reticulum is an early step in a pathway leading to proteasomal degradation of CD4. In this study, regions in the cytoplasmic domain of VpU involved in CD4 binding were identified by NMR spectroscopy. Amino acids in both helices found in the cytoplasmic region of VpU in membrane-mimicking detergent micelles experience chemical shift perturbations upon binding to CD4, whereas amino acids between the two helices and at the C-terminus of VpU show no or only small changes, respectively. The topology of the complex was further studied with paramagnetic relaxation enhancement. Paramagnetic spin labels were attached at three sequence positions of a CD4 peptide comprising the transmembrane and cytosolic domains of the receptor. VpU binds to a membrane-proximal region in the cytoplasmic domain of CD4.
Predictive Testing for DPD Deficiency in a Patient with Familial History of Fluoropyrimidine-Associated Toxicity (2014)

Reduced activity of DPD leads to severe toxicity in cancer patients receiving standard doses of fluoropyrimidines, particularly in the case of combination regimens. We describe a 38-year-old man with a resectable metastasis from hereditary nonpolyposis colorectal cancer, with indication of neoadjuvant chemotherapy and a family history of fluoropyrimidine-associated toxicity. We tested our patient for functional DPYD variants, before any choice of the neoadjuvant regimen, including for the c.496A>G, already described in his mother, and a deep intronic variant c.1129-5923C>G recently reported associated to severe toxicity. Our patient was found to be heterozygous for both c.469A>G and c.1129-5923C>G DPYD variants. We thus offered the most active perioperative regimen, capecitabine, oxaliplatin, irinotecan plus bevacizumab by which we reduced the dosing of capecitabine to 50%. Treatment was well tolerated, with grade 2 diarrhea as the most significant adverse event, and led to a complete pathological response after liver resection. We provide a rationale approach to improve the safety of fluoropirimidine-based therapy in a patient with family history of fluoropyrimidine-associated toxicity.
Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics (2017)

The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit <i>bona fide</i> ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.
ChemInform Abstract: Total Synthesis of (‐)‐Seimatopolide A. (2014)

Abstract Title compound (I) is synthesized in a linear fashion with high yielding steps and utilizing Sharpless asymmetric dihydroxylation, Pd‐catalyzed allylic reduction, and Kitas macrolactonization as the key steps.
Quick Prototype Methodology for Low Offset Thermoplastic Pedestrian Energy Absorbers (2006)

&lt;div class="htmlview paragraph"&gt;This paper describes a methodology to prototype and validate thermoplastic energy absorbers in a broad range of vehicle geometries. The objective of this prototype tool designed with quick prototype methodology is to achieve ready PC/PBT energy absorber designs for pedestrian testing. Generic vehicle models were used to finalize the energy absorber design features. The prototype tool was designed from optimized energy absorber designs that meet pedestrian performance in low packaging space, typically 45–60 mm. A set of prototype tools is being built to match different beam heights and packaging spaces. The tool has also the functionality of achieving different thickness and different design features using the latest manufacturing technologies. A full energy absorber can be built from individual lobes over the width of the car. The finalized design combined with ‘quick prototyping’ methodology was used to finalize the mold design, which can cater to a wide range of vehicle geometries. The prototype designs were validated for different virtual car models. Correlation test was performed between FEA models and prototype molded parts using equivalent rigid impactor test.&lt;/div&gt;
Management of Ventricular Fibrillation with Transvenous Defibrillators Without Baseline Electrophysiologic Testing or Antiarrhythmic Drugs (1996)

After a cardiac arrest due to primary VF, select patients treated with multiprogrammable ICDs can be managed successfully without baseline EPS or antiarrhythmic drug therapy.
FROM SOURCE LOCALIZATION TO BLIND SOURCE SEPARATION: AN INTUITIVE ROUTE TO CONVOLUTIVE BLIND SOURCE SEPARATION (2006)

Most algorithms for blind source separation (BSS) of convolutive speech mixtures are derived in a deductive way from abstract statistical principles and exploit a combination of three signal properties, i.e. nongaussianity, nonwhiteness and nonstationarity. In this paper we show how a separation system can be build the opposite, inductive, way using basic speech processing building blocks. The main block and starting point of our derivation is a simple generalized cross correlation based localization system with two microphones. The capability of source separation (2 signals and 2 sensors) is added by duplicating the localization structure and adding an inhibition mechanism which suppresses already localized sounds. Finally, experimental results with artificially mixed speech signals are presented.
Transcription factor AP-4 is a ligand for immunoglobulin-κ promoter E-box elements (2001)

Immunoglobulin (Ig)-κ promoters from humans and mice share conserved sequences. The octamer element is common to all Ig promoters and pivotal for their function. However, other conserved sequence motifs, that differ between Ig variable gene families, are required for normal promoter function. These conserved motifs do not stimulate transcription in the absence of an octamer. One example is an E-box of the E47/E12 type (5′-CAGCTG-3′), which is found in all promoters of the human and murine Ig-κ gene subgroups/families, with the exception of subgroups II and VI and their related murine families. In the present study we show that the ubiquitously expressed transcription factor AP-4, and not E47, interacts specifically with the κ promoter E-boxes when tested in electrophoretic mobility-shift assays using nuclear extracts derived from human and murine B-cell lines. Furthermore, AP-4, unlike E47, did not act as a transactivator, which is in agreement with previous studies on intact κ promoters, showing that transcription is absent when the octamer element has been mutated. Based on these data, and the conservation of the 5′-CAGCTG-3′ motif among human and murine κ promoters, we propose that AP-4 is the major ligand for Ig-κ promoter E-boxes.
Compounds for reactivation of acetylcholinesterase and related compositions methods and systems (2023)

Described herein are oxime compounds capable of inactivating a nerve agent, blood brain barrier (BBB)-penetration, and/or reactivation of nerve agent-inhibited acetylcholinesterase (AChE) and related methods, systems and compositions for inactivation of one or more nerve agents, therapeutic and/or prophylactic treatment of an individual, and/or decomposition of nerve agent for decontamination.
Efficacy of Nephron-Sparing Surgery for Renal Cell Carcinoma: Analysis Based on the New 1997 Tumor-Node-Metastasis Staging System (1999)

Partial nephrectomy has become an effective method of treating T1 RCC lesions as categorized by both the 1987 and the revised 1997 TNM staging criteria. Selected patients with localized unilateral RCC lesions less than 7 cm (ideally, < 4 cm) and a normal contralateral kidney will benefit from partial nephrectomy.
Binding of Estradiol-17-Fatty Acid Esters to Plasma Proteins* (1987)

The C-17 fatty acid esters of estradiol are a unique family of long-acting estrogens that circulate in blood. The unusual duration of the estrogenic action of these esters has been shown previously to correlate with their very slow rate of metabolism. However, in striking contrast to their slow rate of metabolism, the clearance of these esters from blood is relatively rapid, not very different from that of estradiol (E2). Studies on the effect of the size of the carboxylic acid moiety on the rates of both metabolism and clearance have suggested that an active process might be involved in the cellular uptake of these circulating esters, and this, in turn, raised the question of how E2-fatty acid esters are transported in blood. The binding of representative E2-17-fatty acid esters to both human and rat plasma proteins known to bind either E2 or fatty acids was investigated. As expected, both E2 and 5 alpha-dihydrotestosterone bound to human sex hormone-binding globulin, whereas none of the E2 esters bound to this human plasma protein. Similarly, E2 bound to rat alpha-fetoprotein (AFP) and unsaturated fatty acids bound to both human and rat AFP, but none of the E2 esters bound to AFP of either species. These steroid esters bind to lipoproteins. Over 85% of a representative ester, E2-17-stearate, partitioned in the lipoprotein fractions of both human and rat serum, while the synthetic short chain ester, E2-17 beta-acetate, like E2 itself, partitioned predominantly in the nonlipoprotein fraction of blood. These results demonstrate the unusual binding of a family of steroid hormones to plasma lipoproteins and open the possibility that they are transported into target cells through the mediation of lipoprotein receptors.
Free-Piston Stirling Coolers (1992)

A simple linear analysis of the dynamics of free-piston Stirling coolers is presented to describe the behavior of these machines.Useful results for the displacer phase angle and stroke ratio are obtained and it is shown that the linear analysis is able to accurately account for the dissipative losses in a given machine.A vector diagram is used to indicate the balance of forces at steady operation.This analysis has been used to design a number of successful prototype machines.They include non-CFC domestic refrigeramr coolers, small electronic coolers and a lOOK, 200W lift cryocooler.NOMENCLATUR E a Feed back coupling [N/m] A Displacer cylinder area [m1 AP Piston area [m
NASTransfer: Analyzing Architecture Transferability in Large Scale Neural Architecture Search (2020)

Neural Architecture Search (NAS) is an open and challenging problem in machine learning. While NAS offers great promise, the prohibitive computational demand of most of the existing NAS methods makes it difficult to directly search the architectures on large-scale tasks. The typical way of conducting large scale NAS is to search for an architectural building block on a small dataset (either using a proxy set from the large dataset or a completely different small scale dataset) and then transfer the block to a larger dataset. Despite a number of recent results that show the promise of transfer from proxy datasets, a comprehensive evaluation of different NAS methods studying the impact of different source datasets has not yet been addressed. In this work, we propose to analyze the architecture transferability of different NAS methods by performing a series of experiments on large scale benchmarks such as ImageNet1K and ImageNet22K. We find that: (i) The size and domain of the proxy set does not seem to influence architecture performance on the target dataset. On average, transfer performance of architectures searched using completely different small datasets (e.g., CIFAR10) perform similarly to the architectures searched directly on proxy target datasets. However, design of proxy sets has considerable impact on rankings of different NAS methods. (ii) While different NAS methods show similar performance on a source dataset (e.g., CIFAR10), they significantly differ on the transfer performance to a large dataset (e.g., ImageNet1K). (iii) Even on large datasets, random sampling baseline is very competitive, but the choice of the appropriate combination of proxy set and search strategy can provide significant improvement over it. We believe that our extensive empirical analysis will prove useful for future design of NAS algorithms.
Low Power Passive Equalizer Design for Computer Memory Links (2008)

Several types of low power passive equalizer is proposed and optimized in this work. The equalizer topologies include T-junction, parallel R-C and series R-L structures. These structures can be inserted at driver or/and receiver side at either the chip or package level and the communication bandwidth can be improved with little overhead on power consumption. Using the area of the eye as the objective function to be maximized, we optimized these equalizers for the CPU-memory interconnection of an IBM POWER6trade System with and without practical constraints on the RLCG parameter values. Our experimental results show that without employing any equalizers, the data-eye is closed for a bit-rate of 6.4 Gbps. We tried twelve different equalizer schemes and found they produce very different eye diagrams. The scheme yielding the maximum eye improves the height of the eye to more than 300 mV at a total power cost of 7.2 mW, while the scheme yielding the minimum jitter limits the jitter magnitude to 10 ps at a total power cost of 9.5 mW. We also have shown that the solution resulting from the proposed optimization approach have very small sensitivity to the tolerance of the R,L,C values and the magnitude of the coupled noise.
Effect of Spatial, Temporal and Network Features on Uplink and Downlink Throughput Prediction (2021)

Recently, there have been many attempts to apply Machine Learning (ML)-based prediction mechanisms In wireless networks. One open question is how reliable such predictions can be, and how well ML models can learn from the radio environment. In this paper, we present initial results on Quality of Service (QoS) prediction using the example of throughput prediction. We focus on suggesting new sets of features that can improve the prediction performance for different prediction horizons. Thereby, we identify important features that have a large impact when using radio environment data as input for ML models. To this end, we consider information from space, time, and network domains. In particular, we show that features, such as cell throughput and previous users’ data can significantly improve the ML model performance. Besides the importance of input features, we also investigate how the prediction performance deteriorates for different prediction horizons.
Hypercytokinemia and Hyperactivation of Phospho-p38 Mitogen-Activated Protein Kinase in Severe Human Influenza A Virus Infection (2007)

Hypercytokinemia (of proinflammatory and T helper 1 cytokines) is detected in severe influenza, correlating with clinical illness and virus concentration. Hyperactivation of phospho-p38 mitogen-activated protein kinase (in T helper cells) is possibly involved. Early viral suppression may attenuate these potentially deleterious cytokine responses.
Is phase measurement necessary for incoherent holographic 3D imaging? (2018)

Incoherent digital holography can be used for several applications, among which are high resolution fluorescence microscopy and imaging through a scattering medium. Historically, an incoherent digital hologram has been usually recorded by self-interference systems in which both interfering beams are originated from the same observed object. The self-interference system enables to read the phase distribution of the wavefronts propagating from an object and consequently to decode the 3D location of the object points. In this presentation, we survey several cases in which 3D holographic imaging can be done without the phase information and without two-wave interference.
Novel redox reactions of diazonium fluoroborates. The formation of copper saltazo-compound complexes: water-induced free radical aromatic arylation (1972)

Whereas certain diazonium fluoroborates (ArN2BF4) are stable in benzene at room temperature in the presence of equivalent amounts of copper powder, they react slowly on addition of acetone (10% v/v) to the mixture to give precipitates of red complexes of the azo-compounds (ArN:NAr) with ionic copper. In addition, the free azo-compounds and small (<10%) amounts of biaryls (ArPh) can be isolated. The complexes decompose in water or in polar solvents to give the corresponding azo-compounds. In contrast, when the reaction of the diazonium salt is carried out in the presence of water (2 mol. equiv.), either free or bound in the form of hydrated salts, e.g. magnesium sulphate monohydrate, high yields of biaryls (ArPh) formed by a free radical path are obtained. Azo-complexes are not formed and are not precursors in this reaction, in which copper acts as catalyst.These contrasting observations represent extremes of behaviour of diazonium salts in the presence of copper; the use of smaller quantities of water leads to mixtures of products.The stoicheiometry has been established in each of these reactions and explanations in terms of a series of one-electron, redox reactions of the Waters type are presented.Similar reactions occur with p-chlorobenzenediazonium hexafluorophosphate.
Endovascular Stent-Graft Treatment of a Ruptured Thoracic Aortic Ulcer (2002)

Endovascular stent-graft repair under TEE guidance assists in the oftentimes difficult treatment of ruptured penetrating thoracic aortic ulcer.