gebhart/patrepeval huggingface dataset:
Metabolism of tobacco-specific nitrosamines by cultured rat nasal mucosa. (1983)

The metabolism of two nasal carcinogens, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was investigated using cultured nasal septa of F344 rats. The explants were cultured with 14C-labeled N-nitrosamines, and unbound metabolites present in the medium were quantitated by high-performance liquid chromatography. The results indicated that the mucosa of the nasal septum had a marked capacity to metabolize NNN and NNK to hydroxylated products which were released into the culture media. Extensive activation by alpha-carbon hydroxylation of NNN (preferentially 2'-carbon hydroxylation) and NNK was observed, whereas no deactivation by pyridine N-oxidation could be detected. Microautoradiographic studies of explants showed that binding of radioactivity occurred preferentially in the respiratory and olfactory epithelia and in the subepithelial glands of the nasal mucosa. The results suggest that reactive metabolites of NNN and NNK are formed within the target tissue rather than being transported from the liver to the nasal mucosa. The results also show that the culture of nasal septa can be used to ascertain the role of the nasal mucosa in the activation of nasal-specific carcinogens.
Adaptive Harmonic Control in PWM Inverters with Fluctuating Input Voltage (1986)

New techniques of harmonic reduction and voltage regulation in PWM inverters with fluctuating input voltage are described. A novel selective harmonic reduction technique is also developed for three-phase full-bridge inverters to reduce the number of switchings per output cycle. For keeping the fundamental load voltage at the present value and suppressing the generation of low-order harmonics when the input voltage fluctuates, the conventional sinusoidal reference of the triangulation method is replaced by a quasi-sinewave whose magnitude varies inversely with the input voltage to keep the product of the reference voltage and the input voltage sinusoidal. Harmonic analysis of the W-type modulation and M-type modulation is given to show that the load voltage spectra of the output waveforms generated with the proposed methods are insensitive to the source voltage fluctuation and load variation. Experimental results confirm the theoretical analysis.
Protein farnesylation and disease (2012)

Prenylation consists of the addition of an isoprenoid group to a cysteine residue located near the carboxyl terminal of a protein. This enzymatic posttranslational modification is important for the maturation and processing of proteins. Both processes are necessary to mediate protein-protein and membrane-protein associations, in addition to regulating the localisation and function of proteins. The severe phenotype of animals deficient in enzymes involved in both prenylation and maturation highlights the significance of these processes. Moreover, alterations in the genes coding for isoprenylated proteins or enzymes that are involved in both prenylation and maturation processes have been found to be the basis of severe human diseases, such as cancer, neurodegenerative disorders, retinitis pigmentosa, and premature ageing syndromes. Recent studies on isoprenylation and postprenylation processing in pathological conditions have unveiled surprising aspects of these modifications and their roles in different cellular pathways. The identification of these enzymes as therapeutic targets has led researchers to validate their effects in vitro and in vivo as antitumour or antiageing agents. This review attempts to summarise the basic aspects of protein isoprenylation and postprenylation, integrating our data with that observed in other studies to provide a comprehensive scenario of progeroid syndromes and the therapeutic avenues.
Surface-Enhanced Raman Scattering Studies on Aggregated Gold Nanorods (2003)

Surface-enhanced Raman scattering (SERS) of adsorbed molecules on gold nanorods (NRs) with dimensions of 10 nm × 27 nm was studied on silica surface with low to high surface coverage of NRs. The study was carried out to investigate both the dependence of the SERS intensity on the number of NRs and the NRs spacing on the silica surface. SERS of adsorbed molecules such as 2-aminothiophenol (2-ATP) and the capping molecules (hexadecyltrimethylammonium bromide) was studied on these surfaces using a near-IR laser excitation source (1064 nm). To produce silica surfaces covered with NRs, two approaches were used. In the first approach, monodispersed NRs gradually deposited from solution to silica surface and their number was increased by increasing the deposition time. In the second one, the NRs were first aggregated in solution and then deposited on the surface. Although using the first approach it was possible to prepare surfaces with high NR surface coverage, SERS intensity was found to be stronger for adsorbed molecules on surfaces covered with aggregated NRs. The observed increase in the SERS intensity in the case of aggregation was attributed to the enhancement of the electric field between the particles in the aggregates. It is shown that aggregated NRs in comparison with aggregated nanospheres (NSs) have stronger SERS enhancement under similar experimental conditions. In this comparison, some of the enhanced vibrational bands of 2-ATP on aggregated NRs are weakly enhanced or absent on aggregated NSs. Monitoring the SERS intensity of adsorbed 2-ATP versus its exposure time to the aggregated NRs shows that the SERS intensity of the adsorbed molecules reaches saturation, whereas the peak intensities of the capping molecules remain unchanged. The intensity saturation was discussed in terms of factors such as the saturation of the SERS active sites for 2-ATP on the gold surface and the partial damping of the plasmon band due to the stronger interaction of the adsorbate molecules with the metal surface.
Supporting active reading on pen and touch-operated tabletops (2012)

With the proliferation and sophistication of digital reading devices, new means to support the task of active reading (AR) have emerged. In this paper, we investigate the use of pen-and-touch-operated tabletops for performing essential processes of AR such as annotating, smooth navigation and rapid searching. We present an application to support these processes and then report on a user study designed to compare the suitability of our setup for three typical tasks against the use of paper media and Adobe Acrobat on a regular desktop PC. From this evaluation, we found out that pen and touch tabletops can successfully combine the advantages of paper and digital devices without their disadvantages. We however also learn from observations and participant feedback that there are still a number of hardware and software limitations that impede the user experience and hence need to be addressed in future systems.
High-Resolution Chromosome Sorting and DNA Spot-Blot Analysis Assign McArdle's Syndrome to Chromosome 11 (1984)

A rapid gene-mapping system uses a high-resolution, dual-laser sorter to identify genes from separate human chromosomes prepared with a new stain combination. This system was used to sort 21 unique chromosome types onto nitrocellulose filter papers. Several labeled gene probes hybridized to the sorted chromosomal DNA types predicted by their previous chromosome assignments. The skeletal muscle glycogen phosphorylase gene was then mapped to a portion of chromosome 11 by spot blotting normal and translocated chromosomes.
Abstract A12: Combination of the anti-CD38 monoclonal antibody daratumumab and all-trans retinoic acid. (2015)

Abstract Background: Daratumumab (DARA) is an anti-CD38 monoclonal antibody (mAb) with lytic activity on multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity). In current clinical phase I/II trials, DARA induced anti-MM activity; however, the depth of the response varied between patients. Further improvement of DARA-treatment can be achieved by modulating the mechanisms hampering DARA responsiveness. Results: In a sub-analysis of 16 MM patients treated with DARA monotherapy (GEN501 trial), we observed that response to DARA was associated with baseline CD38 expression levels on the MM cells (R2= 0.40; P= 0.009). We also observed a significant decrease of CD38 expression on MM cells during DARA-treatment (median MFI decreased from 900 to 83). Consistent with this idea, in vitro experiments with isogenic MM cell lines expressing different levels of CD38 have revealed that the level of CD38 expression correlates with DARA-mediated ADCC and CDC. Similarly, in bone marrow samples from 125 and 56 MM patients, we observed a significant correlation between CD38 expression and DARA-mediated ADCC (Pearson R= 0.34; P= 0.&amp;lt;0001) as well as CDC (Pearson R= 0.35; P= 0.0038) respectively. Altogether, this suggested that upregulation of CD38 expression, before and during DARA-treatment, may improve the anti-MM activity of DARA. Indeed, all-trans retinoic acid (ATRA) induced a ~5-fold increase in CD38 expression both in 4 MM cell lines and primary MM cells from 5 DARA-naive patients, which resulted in synergistic improvement of DARA-mediated ADCC and CDC. The synergy between ATRA and DARA was observed not only in DARA-naive patients, but also in 2 DARA-treated patients, whose residual MM cells had lower CD38 expression following therapy. Conclusion: Our results provide evidence that CD38 expression levels may predict response to DARA. Furthermore, we show that ATRA increases CD38 expression on MM cells, resulting in enhanced DARA-mediated lysis of MM cells. Our results provide the preclinical rationale for further evaluation of DARA combined with ATRA in MM patients. Citation Format: Inger S. Nijhof, Henk M. Lokhorst, Berris van Kessel, Parul Doshi, Kate Sasser, Tuna Mutis, Niels WCJ van de Donk. Combination of the anti-CD38 monoclonal antibody daratumumab and all-trans retinoic acid. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A12.
Cone Formation on Metal Targets during Sputtering (1971)

When a Cu surface is sputtered by ion bombardment under the condition that Mo atoms arrive at the Cu surface during sputtering an unexpected phenomenon can arise: The surface of the Cu target becomes covered with microscopic cones. The cone density increases with increasing flux density of arriving Mo atoms. When the cones are closely spaced they give the target a velvet-like black appearance. The result of dense cone coverage is a lower sputtering yield and a more oblique ejection of sputtered material. The cone tops seem to consist of Mo nuclei which are constantly replenished via surface migration and protect the underlying Cu from being sputtered.
Cells with a familial Alzheimerʼs disease mutation produce authentic β-peptide (1993)

Cells overexpressing the beta-amyloid precursor protein possessing a mutation found in familial Alzheimer's disease overproduce beta-amyloid peptide (A beta). Because these findings were based on immunological identification, we have chemically characterized the peptides produced. Purified A beta fragments from the conditioned media of these cells were found to have N-terminal sequence consistent with the A beta found in cerebral plaques. Mass spectrometric data demonstrated a series of A beta fragments consistent with those found in Alzheimer's disease (AD); the major species corresponding to A beta(1-40). Significantly, a longer fragment corresponding to A beta(1-42) was found. These findings suggest that this cellular system may be useful for mechanistic studies of A beta generation and possibly for the development of therapeutic agents to treat AD.
Channels (2014)

What follows is a meditation on a metaphor that continues to provide a way of conceiving our relation to the space of media. It may seem puzzling that I spend as long as I am going to thinking about the prehistory of the idea of the channel in non-communicative contexts. My offer is to try to measure the continuing force of the literality, whatever that may be, of the idea of a channel. Towards the end, I will offer some reflections on the dissolution of the idea of the channel, or of the spatial disposition that has previously constrained what a channel is or can do. I will be saying that the channel depends not upon broadband expression, but on its low bandwidth, on the fact that data must be squeezed through a narrow pipe. My proposition is that decompression of data, the removal of this constraint means a net loss rather than a net gain of information. With no resistance, you can have very high voltage with no amperage. Those of you who want to get quickly to the payload of this piece should scroll through to the last 15 minutes or so. But you can’t if you are istening to this, because this talk is itself a narrow pipe. And, if you could, you would get less information, not more, because there would be less noise for it to have overcome.
Development of a catalytic silicon micro-combustor for hydrocarbon-fueled power MEMS (2003)

This paper reports the development of a high efficiency, hydrocarbon-fueled micro-combustion system for a microscale gas turbine engine for power generation and micro-propulsion applications. A three-wafer catalytic combustor was fabricated and tested. Efficiencies in excess of 40% were achieved for ethylene-air and propane-air combustion. A fabrication process for a six-wafer catalytic combustor was developed and this device was successfully constructed.
Induction coil sensors—a review (2007)

This review describes induction coil sensors, which are also known as search coils, pickup coils or magnetic loop sensors. The design methods for coils with air and ferromagnetic cores are compared and summarized. The frequency properties of coil sensors are analysed and various methods for output signal processing are presented. Special kinds of induction sensors, such as Rogowski coil, gradiometer sensors, vibrating coil sensors, tangential field sensors and needle probes are described. The applications of coil sensors as magnetic antennae are also presented.
HPTS: heterogeneous parallel tabu search for VLSI placement (2003)

Parallelizing any algorithm on a cluster of heterogeneous workstations is not easy, as each workstation requires different wall clock time to execute the same instruction set. In this work, a parallel tabu search algorithm for heterogeneous workstations is presented using PVM. Two parallelization strategies, i.e., functional decomposition and multi-search thread strategies are integrated. The proposed algorithm is tested on the VLSI standard cell placement problem, however, the same algorithm can be used on any combinatorial optimization problem. The results are compared ignoring heterogeneity and are found to be superior in terms of execution time.
What next for human gene therapy? (2003)

The high hope of genetic medicine for 30 years has been to develop a way of using recombinant DNA techniques to treat patients through the genes involved in their diseases. As Richard Roblin, scientific director of the Council on Bioethics of the President of the United States, put it in 1979: “There is something aesthetically compelling about cutting to the heart of the problem, by treating the disease at the molecular level, where it originates.“1 Since 1990, this vision has generated a modest industry of bench research and animal studies, culminating in almost 1000 clinical trials in humans around the world, for a wide variety of diseases.2 In the past few years, however, the field has learned that in genetic medicine, as in war, the “surgical strike“ is rarely as clean and effective as theory implies it should be.
Cutting Edge: Expression of Functional CD137 Receptor by Dendritic Cells (2002)

Interaction between dendritic cells (DCs) and T cells is a prerequisite for the initiation of a T cell response. The molecular nature of this interaction remains to be fully characterized. We report in this work that freshly isolated mouse splenic DCs and bone marrow-derived DCs express CD137 on the cell surface and in soluble form. Triggering CD137 increased the secretion of IL-6 and IL-12 from DCs. More importantly, infusion of an agonistic mAb to CD137 into naive mice enhanced the ability of DCs to stimulate T cell proliferation in response to both alloantigens and a nominal Ag in vitro. This enhancement of DC function is not mediated through activation of T cells, because the effect was also observed in RAG-1 knockout mice that lack T cells. Our findings implicate CD137 as an important receptor involved in the modulation of DC function.
TFIIH-Associated Cdk7 Kinase Functions in Phosphorylation of C-Terminal Domain Ser7 Residues, Promoter-Proximal Pausing, and Termination by RNA Polymerase II (2009)

The function of human TFIIH-associated Cdk7 in RNA polymerase II (Pol II) transcription and C-terminal domain (CTD) phosphorylation was investigated in analogue-sensitive Cdk7(as/as) mutant cells where the kinase can be inhibited without disrupting TFIIH. We show that both Cdk7 and Cdk9/PTEFb contribute to phosphorylation of Pol II CTD Ser5 residues on transcribed genes. Cdk7 is also a major kinase of CTD Ser7 on Pol II at the c-fos and U snRNA genes. Furthermore, TFIIH and recombinant Cdk7-CycH-Mat1 as well as recombinant Cdk9-CycT1 phosphorylated CTD Ser7 and Ser5 residues in vitro. Inhibition of Cdk7 in vivo suppressed the amount of Pol II accumulated at 5' ends on several genes including c-myc, p21, and glyceraldehyde-3-phosphate dehydrogenase genes, indicating reduced promoter-proximal pausing or polymerase "leaking" into the gene. Consistent with a 5' pausing defect, Cdk7 inhibition reduced recruitment of the negative elongation factor NELF at start sites. A role of Cdk7 in regulating elongation is further suggested by enhanced histone H4 acetylation and diminished histone H4 trimethylation on lysine 36-two marks of elongation-within genes when the kinase was inhibited. Consistent with a new role for TFIIH at 3' ends, it was detected within genes and 3'-flanking regions, and Cdk7 inhibition delayed pausing and transcription termination.
On the Mathematical Foundations of Nondifferentiable Optimization in Engineering Design (1987)

It is shown by example that a large class of engineering design problems can be transcribed into the form of a canonical optimization problem with inequality constraints involving mar functions. Such problems are commonly referred to as semi-infinite optimization problems. The bulk of this paper is devoted to the development of a mathematical theory for the construction of first order nondifferentiable optimization algorithms, related to phase I - phase II methods of feasible directions, which solve these semi-infinite optimization problems. The applicability of the theory is illustrated with examples that are relevant to engineering design.
Gene targeting with zinc finger nucleases to produce cloned eGFP knockout pigs (2010)

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Colon-Specific Drug Delivery Based on a Cyclodextrin Prodrug: Release Behavior of Biphenylylacetic Acid from Its Cyclodextrin Conjugates in Rat Intestinal Tracts after Oral Administration (1998)

An antiinflammatory drug biphenylylacetic acid (BPAA) as a model drug was selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta-, and gamma-cyclodextrins (CyDs) through an ester or amide linkage, and the in vivo drug release behavior of these prodrugs in rat gastrointestinal tracts after oral administration was investigated. The CyD prodrugs were stable in rat stomach and small intestine and negligibly absorbed from these tracts. Three to six hours after the oral administration, most of the prodrugs had moved to the cecum and colon. The alpha- and gamma-CyD amide prodrugs were hydrolyzed to the maltose conjugate in the cecum and colon, and these prodrugs and the conjugate were negligibly absorbed. On the other hand, the alpha- and gamma-CyD ester prodrugs produced BPAA in the cecum and colon, and BPAA appeared in the blood after 3-6 h. Both beta-CyD amide and ester prodrugs released only small or negligible amounts of the maltose conjugate or BPAA in the cecum and colon, within 24 h, probably due to the low solubility in the biological media. Further, the antiinflammatory effect of the gamma-CyD ester prodrug was evaluated using the model of carageenan-induced acute edema in rat paw and compared with those of BPAA alone and the BPAA/beta-CyD complex prepared by the kneading method in a molar ratio of 1:1. In the case of the beta-CyD complex, a rapid antiinflammatory response was observed, compared to BPAA alone, because the drug is mainly absorbed from the small intestine after a fast dissolution of the complex. In sharp contrast, the gamma-CyD ester prodrug needed a fairly long lag time to exhibit the drug activity, because BPAA is produced after the prodrug had reached the cecum and colon. The present results clearly suggest that the CyD prodrug approach can provide a versatile means for constructions of not only colon-specific delivery systems but also delayed-release system of certain drugs.
Reducing Pain and Unpleasantness During Repetitive Transcranial Magnetic Stimulation (2006)

Repetitive transcranial magnetic stimulation (rTMS) is associated with significant scalp discomfort under the coil for a high percentage of participants, especially with high stimulation intensities (100% of motor threshold or higher) or frequencies (1 Hz or greater). Some patients in rTMS clinical trials have been unable to tolerate the pain and have dropped out. There seem to be no published studies of strategies to reduce the localized pain and discomfort associated with rTMS. Thus, the authors conducted preliminary pilot trials of 4 different strategies for managing discomfort associated with left prefrontal rTMS. Healthy adults rated the painfulness and unpleasantness of left prefrontal rTMS (10 Hz; 5 seconds, on; 30 seconds, off; at 100% and 120% of resting motor threshold) before and after (1) topical application of a eutectic mixture of local anesthetics cream, (2) scalp injection of lidocaine, (3) scalp injection of lidocaine and epinephrine, and (4) with or without 3 x 3-in thin foam sheets between the coil and scalp. The discomfort produced by rTMS under these experimental conditions was compared with the discomfort produced by stimulation with the same parameters without the interventions. Localized anesthetic injections were associated with a significant decrease in pain intensity and unpleasantness, whereas the eutectic mixture of local anesthetics cream had no effect on rTMS-related discomfort. The use of foam sheets was associated with a slight but noticeable decrease in pain intensity and unpleasantness. More systematic research is needed on the effectiveness of different strategies for reducing rTMS-related pain and discomfort.
Parameter Effects on the Thermal Reaction of Cystine and 2,5-Dimethyl-4-hydroxy-3(2H)-furanone (1989)

The thermal reaction of cystine and DMHF is important for the generation of meat flavors. The products of this reaction, their flavor compounds, aroma profiles and yields, however, vary according to the reaction parameters. This study focused on determining the effect of the reaction medium, duration, water content, temperature, pH and oxygen on the products of this reaction.