gebhart/patrepeval huggingface dataset:
Abstract 2994: Discovery of selective, noncovalent small molecule inhibitors of DNMT1 as an alternative to traditional DNA hypomethylating agents (2018)

Abstract Aberrant DNA hypermethylation within promoter regions and subsequent gene silencing are near universal hallmarks of human cancer. Reversal of DNA methylation by a hypomethylating agent, such as decitabine (Dacogen) or azacytidine (Vidaza), has shown clinical benefit for the treatment of heme malignancies. However, these agents have several limitations that preclude their full potential from being realized such as the requirement for IV administration, poor PK properties and a mechanism that requires incorporation into replicating DNA. This indirect, irreversible inhibition of the DNA methyltransferase (DNMT) family (DNMT1, 3a and 3b) and subsequent DNA damage induces significant dose-limiting toxicity thus preventing sufficient target engagement required for maximal demethylation. A drug discovery effort focused on DNMT1, the key family member responsible for maintaining the DNA methylation pattern, was initiated based on the compelling nature of the target coupled with the need for improved agents. A high-throughput screen identified a single dicyanopyridine (DCP) series of reversible, non-DNA incorporating, highly selective inhibitors for DNMT1 over DNMT3a or DNMT3b. Ensuing structure-activity relationship (SAR) optimization of the series led to the discovery of potent tool compounds that in cancer cells induced robust decreases in global DNA methylation, transcriptional activation of many silenced genes, and inhibition of cancer cell growth. In contrast to decitabine where most cells showed a cytotoxic response, our DNMT1 tool inhibitors primarily elicited a cytostatic response. Furthermore, studies in a mouse tumor model revealed decreased DNA methylation and a dose-dependent (1-45 mg/kg, BID) decrease in tumor growth with regression at the highest doses. In summary, a series of potent, selective DNMT1 inhibitors were discovered and refined delivering tool compounds capable of eliciting changes in DNA methylation, transcriptional activation, and tumor regression at well-tolerated doses. Thus demonstrating that selective, non-covalent inhibitors of DNMT1 may provide benefit over traditional DNA incorporating hypomethylating agents. Citation Format: Melissa B. Pappalardi, Mark Cockerill, Jessica L. Handler, Alexandra Stowell, Kathryn Keenan, Christian S. Sherk, Elisabeth A. Minthorn, Charles F. McHugh, Charlotte Burt, Kristen Wong, David T. Fosbenner, Mehul Patel, Jacques Briand, Helai Mohammad, Lourdes Rueda, Andrew Benowitz, Rab Prinjha, Dirk Heerding, Ryan G. Kruger, Ali Raoof, Allan Jordan, Bryan W. King, Michael T. McCabe. Discovery of selective, noncovalent small molecule inhibitors of DNMT1 as an alternative to traditional DNA hypomethylating agents [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 2994.
Organic Solvent Nanofiltration – Challenges and Approaches of an Innovative Membrane Separation Process (2014)

Abstract Die Kopplung innovativer Trenntechnologien mit konventionellen verfahrenstechnischen Grundoperationen besitzt ein großes Potential, um den Lösungsmittel‐ und Energiebedarf zu verbessern. Ein Beispiel ist die organophile Nanofiltration, ein druckgetriebenes Membrantrennverfahren, das in organischen Lösungsmitteln eingesetzt werden kann. Die Herausforderungen liegen insbesondere im konzeptionellen und detaillierten Prozessentwurf. In dieser Arbeit wurden verschiedene Werkzeuge entwickelt, in einem fünfschrittigen Arbeitsschema zusammengefasst und anhand eines Fallbeispiels veranschaulicht.
Metabolism of Dietary Polyphenols and Possible Interactions with Drugs (2007)

Polyphenolic compounds are abundant in the human diet and gram quantities are ingested daily. The consumption of polyphenols is expected to rise due to the use of dietary supplements and public health initiatives promoting the consumption of more fruits and vegetables. It is known that these dietary polyphenols are extensively metabolized. Many of these compounds are therefore are expected to compete with other substrates of Phases I, II, III enzymes and transporters. In addition, some dietary polyphenols may induce certain drug metabolizing enzymes and affect the metabolism of important therapeutic agents. This review will discuss 1) the metabolism of dietary polyphenols using green tea polyphenols (catechins) as an example, 2) inhibition of drug metabolism by polyphenols, and 3) induction of drug metabolizing enzymes by dietary polyphenols. The potential consequences of these effects on drug metabolism will also be discussed.
IAP inhibitors enhance co-stimulation to promote tumor immunity (2010)

The inhibitor of apoptosis proteins (IAPs) have recently been shown to modulate nuclear factor κB (NF-κB) signaling downstream of tumor necrosis factor (TNF) family receptors, positioning them as essential survival factors in several cancer cell lines, as indicated by the cytotoxic activity of several novel small molecule IAP antagonists. In addition to roles in cancer, increasing evidence suggests that IAPs have an important function in immunity; however, the impact of IAP antagonists on antitumor immune responses is unknown. In this study, we examine the consequences of IAP antagonism on T cell function in vitro and in the context of a tumor vaccine in vivo. We find that IAP antagonists can augment human and mouse T cell responses to physiologically relevant stimuli. The activity of IAP antagonists depends on the activation of NF-κB2 signaling, a mechanism paralleling that responsible for the cytotoxic activity in cancer cells. We further show that IAP antagonists can augment both prophylactic and therapeutic antitumor vaccines in vivo. These findings indicate an important role for the IAPs in regulating T cell-dependent responses and suggest that targeting IAPs using small molecule antagonists may be a strategy for developing novel immunomodulating therapies against cancer.
RETRACTED: Batched matrix computations on hardware accelerators based on GPUs (2015)

Scientific applications require solvers that work on many small size problems that are independent from each other. At the same time, the high-end hardware evolves rapidly and becomes ever more throughput-oriented and thus there is an increasing need for an effective approach to develop energy-efficient, high-performance codes for these small matrix problems that we call batched factorizations. The many applications that need this functionality could especially benefit from the use of GPUs, which currently are four to five times more energy efficient than multicore CPUs on important scientific workloads. This paper, consequently, describes the development of the most common, one-sided factorizations, Cholesky, LU, and QR, for a set of small dense matrices. The algorithms we present together with their implementations are, by design, inherently parallel. In particular, our approach is based on representing the process as a sequence of batched BLAS routines that are executed entirely on a GPU. Importantly, this is unlike the LAPACK and the hybrid MAGMA factorization algorithms that work under drastically different assumptions of hardware design and efficiency of execution of the various computational kernels involved in the implementation. Thus, our approach is more efficient than what works for a combination of multicore CPUs and GPUs for the problems sizes of interest of the application use cases. The paradigm where upon a single chip (a GPU or a CPU) factorizes a single problem at a time is not at all efficient in our applications' context. We illustrate all of these claims through a detailed performance analysis. With the help of profiling and tracing tools, we guide our development of batched factorizations to achieve up to two-fold speedup and three-fold better energy efficiency as compared against our highly optimized batched CPU implementations based on MKL library. The tested system featured two sockets of Intel Sandy Bridge CPUs and we compared with a batched LU factorizations featured in the CUBLAS library for GPUs, we achieve as high as 2.5× speedup on the NVIDIA K40 GPU.
Adaptive sampling of CT data for myocardial blood flow estimation from dose-reduced dynamic CT (2015)

Quantification of myocardial blood flow (MBF) can aid in the diagnosis and treatment of coronary artery disease (CAD). However, there are no widely accepted clinical methods for estimating MBF. Dynamic CT holds the promise of providing a quick and easy method to measure MBF quantitatively, however the need for repeated scans has raised concerns about the potential for high radiation dose. In our previous work, we explored techniques to reduce the patient dose by either uniformly reducing the tube current or by uniformly reducing the number of temporal frames in the dynamic CT sequence. These dose reduction techniques result in very noisy data, which can give rise to large errors in MBF estimation. In this work, we seek to investigate whether nonuniformly varying the tube current or sampling intervals can yield more accurate MBF estimates. Specifically, we try to minimize the dose and obtain the most accurate MBF estimate through addressing the following questions: when in the time attenuation curve (TAC) should the CT data be collected and at what tube current(s). We hypothesize that increasing the sampling rate and/or tube current during the time frames when the myocardial CT number is most sensitive to the flow rate, while reducing them elsewhere, can achieve better estimation accuracy for the same dose. We perform simulations of contrast agent kinetics and CT acquisitions to evaluate the relative MBF estimation performance of several clinically viable adaptive acquisition methods. We found that adaptive temporal and tube current sequences can be performed that impart an effective dose of about 5 mSv and allow for reductions in MBF estimation RMSE on the order of 11% compared to uniform acquisition sequences with comparable or higher radiation doses.
Anti-Inflammatory Properties of Bioactive Compounds from Medicinal Plants (2020)

Consumption of medicinal plants exerts a promising role in drug discovery that has proven very effective against various human syndromes. Diallyl trisulfide (DATS) suppresses naphthalene-induced oxidative injury and inhibits inflammatory responses, such as TNF-α, IL-6, IL-8, and nuclear factor-kappa B (NF-κB). DATS also suppresses the production of serum nitric oxide (NO) and myeloperoxidase (MPO). The 6-Gingerol can enhance the anti-inflammatory cytokine interleukin-10 and reduce the expression of monocyte chemotactic protein-1, TNF-α, interleukin-1β, and interleukin-6. Lupeol inhibits the stimulation and production of osteoclastogenesis of macrophages in a concentration-dependent manner. They momentously decrease the formation of pro-inflammatory cytokines (IL-6, IL-1β, IL-12, and TNF-α), and lead to an increase in the production of p38 mitogen-activated protein kinase (MAPK).
LINGO-1 Regulates Oligodendrocyte Differentiation through the Cytoplasmic Gelsolin Signaling Pathway (2017)

Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. However, how actin dynamics are regulated during this process remains poorly understood. Leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1 (LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody-promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments. Treating rat OPCs with cGSN siRNA reduced OPC differentiation, whereas overexpression of cGSN promoted OPC differentiation <i>in vitro</i> and remyelination <i>in vivo</i> Furthermore, coexpression of cGSN and LINGO-1 blocked the inhibitory effect of LINGO-1. Our study demonstrates that cGSN works downstream of LINGO-1 signaling pathway, which enhances actin dynamics and is essential for OPC morphogenesis and differentiation. This finding may lead to novel therapeutic approaches for the treatment of demyelinating diseases such as multiple sclerosis (MS).<b>SIGNIFICANCE STATEMENT</b> Myelin loss and subsequent axon degeneration contributes to a variety of neurological diseases, such as multiple sclerosis (MS). Understanding the regulation of myelination by oligodendrocytes is therefore critical for developing therapies for the treatment of MS. We previously demonstrated that leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1 (LINGO-1) is a negative regulator of oligodendrocyte differentiation and that anti-LINGO-1 promotes remyelination in preclinical animal models for MS and in a phase II acute optic neuritis clinical trial (RENEW). The mechanism by which LINGO-1 regulates oligodendrocyte differentiation is unknown. Here, we demonstrate that LINGO-1 regulates oligodendrocyte differentiation and maturation through the cytoplasmic gelsolin signaling pathway, providing new drug targets for the treatment of demyelination diseases.
Adsorption properties in high optical quality nanoZIF-8 thin films with tunable thickness (2010)

We report processing of a thin film by chemical solution deposition of a microporous ZIF-8 nanoparticle dispersion. By using the drain and capillary regimes involved in the dip-coating process, we tuned the thickness of the films from 40 nm to 1 μm and controlled the packing of the nanoparticles on the substrate. The high optical quality thin films show a dual hierarchical porous structure from the micropores of the framework and the mesoporous interparticular voids. Moreover, vapor sorption properties of the microporous ZIF-8 based thin films have been evaluated by ellipsometric porosimetry. The hydrophobic films show alcohol, THF and hydrocarbon adsorption. Experiments for isopropanol/water separation have been carried out and the selective adsorption of the alcohol versus the water makes these thin films good candidates for vapor sensors.
Randomized sample-level interpolation for audio content manipulation (2012)

In this paper we propose a novel audio signal manipulation algorithm based on sample-level interpolations that can generate multiple unique versions of an audio file without creating any perceptual difference. The proposed algorithm enables important applications such as digital rights management and file distribution tracking. The simplest sample-level interpolation method is based on time domain interpolation of fixed-length audio frames. The processing algorithm first segments the audio signal into fixed-length frames. For each frame, we perform a slight time compression or extension using an audio sample interpolation algorithm and then we recombine the manipulated audio samples to form a manipulated version of the original audio files. To enable better security features a randomization program is applied to control the frame-length and manipulation-length using pseudo-random sequences. The result of this algorithm is effectively a form of weak frequency modulation. If the fame size is larger than the compression/extension sample number, these compression/extension manipulations will not produce any audible difference. Various subjective evaluation experiments are conducted to decide the extent of the admissible processing parameters that will not cause noticeable difference in both fixed-length and randomized-length sample manipulation. The authors also provide several implementation examples and a brief summary.
<title>Customized schematic eye model for refraction correction design based on ocular wavefront and corneal topography measurements</title> (2002)

The subject of this paper relates to the ocular optical design and vision analysis of refractive correction of the eye. After the purpose statement and the assumption list, the concept of the schematic eye matching a particular (measured) wavefront is introduced. This concept is based on the fact that the ocular wavefront, together with the corneal topography, can be seen as the mathematical global representation of the eye working in monochromatic light and having a foveal vision. The discussed design technique, including an iterative optimization method, could be applied in any ocular correction that utilizes cornea topography and/or ocular wavefront, e.g. contact lens or intra-corneal implant. However, the application this paper refers to is the ocular refractive correction by a procedure using the LADARVISION. It consists of surgical removal and subsequent replacement of a corneal flap on a stromal surface whose shape has been changed by laser ablation of the tissue. Subsequent sections of this paper are dedicated to establishing the limits of possible refractive correction, the influences of the flap and corneal topography into the refractive correction calculation. Finally a realistic evaluation of the results and a list of possible developments of this new optical design method are discussed.
Data management, IN services and interworking in DAWN-a distributed architecture for wireless PCS networks: an overview (2002)

We present enhancements for a wireless PCS architecture which distributes processing from the mobile switching centers and cell sites. In a wireless environment all the call processing components need access to the subscriber data. The subscriber profile distributing scheme envisioned for this architecture provides a method to localize data in clusters and access it remotely, which leads to a reduction in service profile transfers and better load sharing. Our propagation model of service profile transfers also reduces the number of times service profile updating is required. We also introduce a way to incorporate wireless intelligent network services in the call control phase and provide processing of these services in a distributed manner. The interworking needed to allow coexistence with conventional wireless networks is also presented.
Influence of Microwave Radiation on the Growth of Gold Nanoparticles and Microporous Zincophosphates in a Reverse Micellar System (2006)

The water core of reverse micelles has been extensively used as the site for synthesis of a variety of materials. However, water-in-oil reverse micelles have a limited range of temperatures over which they are stable as a single phase. Directing heat to the water cores, the usual site of synthesis without heating the bulk provides added opportunities for synthesis. Microwave radiation is a method for superheating the water cores. In this study, we use an H2O-sodium bis(2-ethylhexyl) sulfosuccinate (AOT)-heptane reverse micelle system for the synthesis of Au particles by hydrazine reduction of HAuCl4 in the presence and absence of microwave radiation. The duration of the microwave radiation was limited to a 2-min duration at a power of 300 W, thereby ensuring that the reverse micelle phase is maintained during the synthesis. At all hydrazine concentrations studied (0.5-2 M), the presence of microwave radiation led to an increase in the particle size of Au. The second system examined was the growth of microporous zincophosphate-X (ZnPO-X, an analogue of the faujasite structure) synthesized from H2O-dioctyldimethylammonium chloride (DODMAC)-heptane reverse micelle system. Microwave radiation was applied for 1 min at 150 W at various stages of the nucleation and growth process, and did not disrupt the reverse micelle system. Product analysis after 48 h of reaction showed that the 1-min microwave pulse, if applied during the nucleation stage (the first 4 h), promoted the formation of NaZnPO4.H2O over ZnPO-X. The effect of the microwave pulse at the growth stage was to promote the formation of ZnPO-X. Absorption of the microwave radiation by the water core and surrounding polar surfactant molecules leads to a rapid rise in local temperature (predicted to be approximately 150 degrees C/min for the AOT system), increasing the rates of intramicellar reactions.
Operation principle and perspective performances of Metal Oxide Vacuum Field Effect Transistor - MOVFET (2020)

In this paper we present the operation principle of a Metal Oxide Vacuum Field Effect Transistor (MOVFET). The idea is to exploit a technology proposed in the literature to realize nano devices with low threshold voltage for power applications. The principle of operation of the MOVFET is based on the emission of electrons from a cold cathode in a vacuum in such a way to obtain a pentode-like characteristics with a very low on resistance. This last feature is particularly interesting for the application as switches in power electronics applications. Moreover, the absence of a gate oxide which is always present in traditional MOSFETs suggests that this device can have better reliability features even in rad hard applications. A numerical simulator is used to evaluate the impact of the technological parameters on the static characteristics of the device and the perspective performances in power electronics applications.
Diffraction of optical communication Gaussian beams by volume gratings: comparison of simulations and experimental results (2004)

The diffraction effects induced by a thick holographic grating on the propagation of a finite Gaussian beam are theoretically analyzed by means of the coupled-wave theory and the beam propagation method. Distortion of the transmitted and diffracted beams is simulated as a function of the grating parameters. Theoretical results are verified by experimentation realized by use of LiNbO3 volume gratings read out by a 1550-nm Gaussian beam, typical of optical fiber communications. This analysis can be implemented as a useful tool to aid with the design of volume grating-based devices employed in optical communications.
Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia (1984)

Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.