gebhart/patrepeval huggingface dataset:
Discovery and Optimization of a Series of Carbazole Ureas as NPY5 Antagonists for the Treatment of Obesity (2002)

The hypothesis that antagonists of the neuropeptide Y5 receptor would provide safe and effective appetite suppressants for the treatment of obesity has prompted vigorous research to identify suitable compounds. We discovered a series of acylated aminocarbazole derivatives (e.g., 3a) that are potent and selective Y5 antagonists, representing interesting starting points but suffering from poor bioavailability and concerns about potential toxicity as a consequence of the embedded aminocarbazole fragment. It proved relatively easy to improve the drug metabolism and pharmacokinetic (DMPK) properties by variation of the side chain (as in 4a) but difficult to eliminate the aminocarbazole fragment. For compounds in this series to have the potential to be drugs, we believed that both the compound itself and the component aniline must be free of mutagenic activity. Parallel structure-activity relationship studies looking at the effects of ring substitution have proved that it is possible by incorporation of a 4-methyl substituent to produce carbazole ureas with potent Y5 activity, comprised of carbazole anilines that in themselves are devoid of mutagenic activity in the Ames test. Compound 4o (also known as NPY5RA-972) is highly selective with respect to Y1, Y2, and Y4 receptors (and also to a diverse range of unrelated receptors and enzymes), with an excellent DMPK profile including central nervous system penetration. NPY5RA-972 (4o) is a highly potent Y5 antagonist in vivo but does not block neuropeptide Y-induced feeding nor does it reduce feeding in rats, suggesting that the Y5 receptor alone has no significant role in feeding in these models.
Processing of telomeric DNA ends requires the passage of a replication fork (1998)

During telomere replication in yeast, chromosome ends acquire a long single-stranded extension of the strand making the 3' end. Previous work showed that these 3' tails are generated late in S-phase, when conventional replication is virtually complete. In addition, the extensions were also observed in cells that lacked telomerase. Therefore, a model was proposed that predicted an activity that recessed the 5' ends at yeast telomeres after conventional replication was complete. Here, we demonstrate that this processing activity is dependent on the passage of a replication fork through yeast telomeres. A non-replicating linear plasmid with telomeres at each end does not acquire single-stranded extensions, while an identical construct containing an origin of replication does. Thus, the processing activity could be associated with the enzymes at the replication fork itself, or the passage of the fork through the telomeric sequences allows a transient access for the activity to the telomeres. We therefore propose that there is a mechanistic link between the conventional replication machinery and telomere maintenance.
Enhancing degraded document images via bitmap clustering and averaging (2002)

Proper display and accurate recognition of document images are often hampered by degradations caused by poor scanning or transmission conditions. The authors propose a method to enhance such degraded document images for better display quality and recognition accuracy. The essence of the method is in finding and averaging bitmaps of the same symbol that are scattered across a text page. Outline descriptions of the symbols are then obtained that can be rendered at arbitrary solution. The paper describes details of the algorithm and an experiment to demonstrate its capabilities using fax images.
Myeloma and Osteolytic Bone Disease: Is DKK1 All It Takes?. (2008)

Abstract The Dickkopf-1 (DKK1) gene product inhibits osteoblast activity by blocking Wnt signaling. Elevated levels of DKK1 in bone marrow plasma and peripheral blood are associated with the presence of osteolytic bone lesions in patients with multiple myeloma (Tian E, et al. N Engl J Med.2003, 349:2483), evidently by inhibiting osteoblast differentiation and, as a result, stimulating osteoclastogenesis driven by osteoblast progenitors’ enhanced production of RANKL and reduced expression of OPG. DKK1-neutralizing antibody suppressed bone resorption induced by inflammatory joint disease and myeloma in murine models (Diarra, Nature Medicine2007, 13:156, Yaccoby, Blood2007, 109:2106), and ectopic Wnt3a expression prevented myeloma induced bone resoption (Qiang, Blood2008;112:374). To further investigate whether DKK1 is essential for producing myeloma bone disease, we used 5 myeloma cell lines with various expression levels of DKK1 in our SCID-hu model. U266 and CAG cells, which express minimal amounts of DKK1 mRNA by qRT-PCR corresponding to 5ng/ml in spent media by ELISA, caused severe bone resorption, whereas ARP1, H929 and OPM2 which express 55, 61, and 320 fold higher levels of DKK1 mRNA (and 80 ng/ml protein for ARP1 cells) had no effects on the bones. OPM2 cells overexpressing DKK1 following transduction with lentiviral vector (127 fold higher than U266 cells), also did not cause bone resorption. To understand if the lack of relationship between DKK1 expression by myeloma cell lines and bone resorption reflected the level of expression, we used the prostate cancer cell line PC3 that expresses 100 times higher DKK1 mRNA than DKK1-transduced OPM2 cells. These cells caused severe bone destruction in the SCID-hu model. DKK1 expression by PC3 was inhibited by 80% by constitutive or conditional (tet-on) shRNA-lentivirus, and resulted in corresponding reduction (75%, p=0.02) in loss of bone mineral density compared with control cells transduced with conditional or constitutive control shRNA lentivirus. PC3 cells recovered from the tumors had 50% reduced levels of DKK1 mRNA. Myeloma associated osteolytic bone disease results from inhibition of osteoblast differentiation, resulting in reduced bone formation and overcharged osteoclastogenesis by osteoblast progenitors. It thus appears that a quantitative threshold exists below which DKK1 inhibition of Wnt is not sufficient to cause osteolytic bone disease. Alternatively, it is possible that the DKK1 produced by the MM cell lines is not funtional, or that factors other than inhibition of Wnt signaling by DKK1 can also be responsible for producing osteolytic bone disease. We are currently investigating whether direct stimulation of osteoclastic activity by the myeloma cell lines that cause osteolysis but express low DKK1 can explain this observed discrepancy, or if they inhibit osteoblast differentiation by other mechanisms. This work was supported in part by NIH grant CA55816.
Application of Ultrasonics to Nonintrusive Vibration Measurement (1993)

This paper outlines a nonintrusive vibration measurement method using standard, off-the-shelf commercial ultrasonic instruments designed for flaw detections, together with digital signal analysis techniques. This method was incorporated into a commercial package designed for nonintrusive check valve monitoring and has been extensively tested in both the laboratory and the field. It can detect valve disk flutter as small as 0.02-in. (0.50 mm) peak-to-peak, without disassembly of the valve. In simulated tests, it quantitatively measured, remotely and nonintrusively, stationary vibration amplitudes as small as 0.0001 in. (0.0025 mm). Other potential applications include in-service vibration monitoring of internal components of nuclear reactors, steam generators, heat exchangers, pumps and valves, and in the laboratory or in the field, when the vibration frequency is too low for accelerometers and the strain is too low for strain gages.
Study on Superconducting Levitation System for Gravity Measurement (2019)

A high precision superconducting levitation system for gravity measurement has been developed, which used the levitation of a superconducting sphere by the magnetic field of two superconducting coils. The magnetic levitation is designed to provide independent adjustment of the levitating force and the force gradient. A Gifford-McMahon (GM) cryocooler is employed to cool down the system. This paper reviews the construction and operating characteristics of the system. The test results show that the earth tide signal was detected by the system.
An Algorithm for Computing IP/LDP Fast Reroute Using Maximally Redundant Trees (MRT-FRR) (2016)

This document supports the solution put forth in "An Architecture for IP/LDP Fast Reroute Using Maximally Redundant Trees (MRT-FRR)" (RFC 7812) by defining the associated MRT Lowpoint algorithm that is used in the Default MRT Profile to compute both the necessary Maximally Redundant Trees with their associated next hops and the alternates to select for MRT-FRR.
Proposal and Experimental Results of Disordered Crystalline Semiconductors (1989)

A new semiconductor which exhibits unusual luminescent capability is proposed, and experimental results of photoluminescence to confirm the proposal are reported. The semiconductor can be called as a “disordered crystalline semiconductor”, since the atomic arrangement is disordered but single-crystal epitaxial growth is possible.
A facile synthesis of 2‐substituted‐4‐(substituted)phenyl‐Δ<sup>2</sup>‐1,3,4‐oxadiazolin‐5‐ones (1977)

Abstract The title compounds, 3, are formed at ambient temperature from 4,4‐dimethyl‐2‐(substituted)‐phenylsemicarbazides (1) and carboxylic acid chlorides in the presence of triethylamine. 2‐Dimethylamino‐4‐(substiluted)phenyl‐Δ 2 ‐1,3,4‐oxadiazolin‐5‐ones are formed from 1 and dialkyl‐carbamoyl chlorides at elevated temperature (about 15° ). Acylation of 1 with carboxylic acid anhydrides, also at elevated temperature, is accompanied by loss of dimethylamine from the intermediate l‐acyl‐4,4‐dimethyl‐2‐(substituted)phenylsemicarbazides, 2, to give 3.
An efficient technique for protecting location privacy of cooperative spectrum sensing users (2016)

Cooperative spectrum sensing, despite its effectiveness in enabling dynamic spectrum access, suffers from location privacy threats, merely because secondary users (SUs)' sensing reports that need to be shared with a fusion center to make spectrum availability decisions are highly correlated to the users' locations. It is therefore important that cooperative spectrum sensing schemes be empowered with privacy preserving capabilities so as to provide SUs with incentives for participating in the sensing task. In this paper, we propose an efficient privacy preserving protocol that uses an additional architectural entity and makes use of various cryptographic mechanisms to preserve the location privacy of SUs while performing reliable and efficient spectrum sensing. We show that not only is our proposed scheme secure and more efficient than existing alternatives, but also achieves fault tolerance and is robust against sporadic network topological changes.
Identification of Mosquito Biting Deterrent Constituents From the Indian Folk Remedy Plant Jatropha curcas (2011)

An investigation of the Indian folk remedy plant Jatropha curcas L., was performed to identify the constituents responsible for the mosquito biting deterrent activity of the oil. J. curcas seed oil is burned in oil lamps in India and parts of Africa to repel biting insects, primarily mosquitoes. The seed oil was thoroughly analyzed by 1H NMR, 13C NMR, high-performance liquid chromatography-refractive index, and gas chromatography-flame ionization detection to identify the constituents in the oil. Identified constituents, both free fatty acids and triglycerides, were evaluated for activity in Aedes aegypti (L.) (Diptera: Culicidae) biting deterrent assays. Furthermore, an oil condensation trap was used to demonstrate that free fatty acids or triglycerides are partially volatilized during the combustion process. These compounds were found to be responsible for the biting deterrency of the burned oil. Specifically, oleic, palmitic, linoleic, and stearic acids were all active at 25 nmol/cm2 above that of solvent control in Ae. aegypti biting deterrent assays. Oleic, palmitic, and linoleic acids were all more active than stearic acid in the same bioassay. Evaluation of the triglycerides containing each of these fatty acids revealed that tripalmitin, tristearin, trilinolein, and triolein all demonstrated significant activity above a solvent control at 10 microg/cm2, whereas tripalmitin was the most active. Due to literature reports suggesting larvicidal activity of the oil, J. curcas seed oil and its free fatty acid constituents also were evaluated against 1-d-old Ae. aegypti larvae up to 500 ppm. Oleic acid was the only fatty acid having larvicidal activity against 1-d-old Ae. aegypti larvae, with an LD50 of 47.9 ppm.
Vacuole-Localized Berberine Bridge Enzyme-Like Proteins Are Required for a Late Step of Nicotine Biosynthesis in Tobacco1   (2011)

Tobacco (Nicotiana tabacum) plants synthesize nicotine and related pyridine-type alkaloids, such as anatabine, in their roots and accumulate them in their aerial parts as chemical defenses against herbivores. Herbivory-induced jasmonate signaling activates structural genes for nicotine biosynthesis and transport by way of the NICOTINE (NIC) regulatory loci. The biosynthesis of tobacco alkaloids involves the condensation of an unidentified nicotinic acid-derived metabolite with the N-methylpyrrolinium cation or with itself, but the exact enzymatic reactions and enzymes involved remain unclear. Here, we report that jasmonate-inducible tobacco genes encoding flavin-containing oxidases of the berberine bridge enzyme family (BBLs) are expressed in the roots and regulated by the NIC loci. When expression of the BBL genes was suppressed in tobacco hairy roots or in tobacco plants, nicotine production was highly reduced, with a gradual accumulation of a novel nicotine metabolite, dihydromethanicotine. In the jasmonate-elicited cultured tobacco cells, suppression of BBL expression efficiently inhibited the formation of anatabine and other pyridine alkaloids. Subcellular fractionation and localization of green fluorescent protein-tagged BBLs showed that BBLs are localized in the vacuoles. These results indicate that BBLs are involved in a late oxidation step subsequent to the pyridine ring condensation reaction in the biosynthesis of tobacco alkaloids.
DIMPL: a distributed in-memory drone flight path builder system (2018)

Drones are increasingly being used to perform risky and labor intensive aerial tasks cheaply and safely. To ensure operating costs are low and flights autonomous, their flight plans must be pre-built. In existing techniques drone flight paths are not automatically pre-calculated based on drone capabilities and terrain information. Instead, they focus on adaptive shortest paths, manually determined paths, navigation through camera, images and/or GPS for guidance and genetic or geometric algorithms to guide the drone during flight, all of which makes flight navigation complex and risky. In this paper we present details of an automated flight plan builder DIMPL that pre-builds flight plans for drones tasked with surveying a large area to take photographs of electric poles to identify ones with hazardous vegetation overgrowth. The flight plans are built for subregions allowing the drones to navigate autonomously. DIMPL employs a distributed in-memory paradigm to process subregions in parallel and build flight paths in a highly efficient manner. Experiments performed with network and elevation datasets validated the efficiency of DIMPL in building optimal flight plans for a fleet of different types of drones and demonstrated the tremendous performance improvements possible using the distributed in-memory paradigm.
The <i>LOC387715 </i>Gene, Smoking, Body Mass Index, Environmental Associations with Advanced Age-Related Macular Degeneration (2007)

The number of risk alleles at the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1-4.3) for the GT heterozygous genotype and OR = 12.1 (5.6-26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The LOC387715 SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between LOC387715 genotype and smoking with regard to advanced AMD development.
Emotional space improves emotion recognition (2002)

A number of recent studies have focused on the conceptualized expression of emotions as a three-dimensional space.This paper proposes a new approach to emotion recognition, making use of two of the emotional dimensions and their relationship with different kinds of features.The main idea consists in associating prosodic features, derived from pitch, loudness, and duration, with the activation or arousal dimension, and quality features, i.e. phonation type, articulation manner, voice timbre, with the evaluation and pleasure dimension, in a way that different classification methods can be applied for each specific case.Most important results are achieved for the speaker-independent case and three classes, with a recognition rate close to 80%.
<title>Signal/background separation by wavelet packets for detection of microcalcifications in mammograms</title> (1996)

We developed a method of weighted wavelet packets for separation of small, low contrast signals from large, inhomogeneous background. Our method was applied to the enhancement of microcalcifications on digital mammograms, which appear as small bright spots superimposed on the background representing the structure of breast tissue, for improvement of the performance of our computer-aided diagnosis scheme for detection of clustered microcalcifications. Our method first approximates signals if interest by a set of wavelets that are extracted from a wavelet packet dictionary by means of the matching pursuit algorithm. The selected set of wavelets is then subjected to a supervised learning process for optimization of the weights assigned to individual time-frequency tiles for enhancement of the microcalcifications and suppression of the background structures. In an analysis of 82 regions of interest extracted from our mammographic database, our new method showed a sensitivity of 92 percent and a specificity of 75 percent. Our new method is shown to perform better than our previous method based on the fixed-weight, orthogonal wavelet transform.
BCL2A1 regulates Canady Helios Cold Plasma-induced cell death in triple-negative breast cancer (2022)

Breast cancer is the leading cause of cancer death among women. Triple-negative breast cancer (TNBC) has a poor prognosis and frequently relapses early compared with other subtypes. The Cold Atmospheric Plasma (CAP) is a promising therapy for prognostically poor breast cancer such as TNBC. The Canady Helios Cold Plasma (CHCP) induces cell death in the TNBC cell line without thermal damage, however, the mechanism of cell death by CAP treatment is ambiguous and the mechanism of resistance to cell death in some subset of cells has not been addressed. We investigate the expression profile of 48 apoptotic and 35 oxidative gene markers after CHCP treatment in six different types of breast cancer cell lines including luminal A (ER<sup>+</sup> PR<sup>+/-</sup>HER2<sup>-</sup>), luminal B (ER<sup>+</sup>PR<sup>+/-</sup>HER2<sup>+</sup>), (ER<sup>-</sup>PR<sup>-</sup>HER2<sup>+</sup>), basal-like: ER<sup>-</sup>PR<sup>-</sup>HER2<sup>-</sup> cells were tested with CHCP at different power settings and at 4 different incubation time. The expression levels of the gene markers were determined at 4 different intervals after the treatment. The protein expression of BCL2A1 was only induced after CHCP treatment in TNBC cell lines (p < 0.01), whereas the HER2-positive and ER, PR positive cell lines showed little or no expression of BCL2A1. The BCL2A1 and TNF-alpha expression levels showed a significant correlation within TNBC cell lines (p < 0.01). Silencing BCL2A1 mRNA by siRNA increased the potency of the CHCP treatment. A Combination of CHCP and CPI203, a BET bromodomain inhibitor, and a BCL2A1 antagonist increased the CHCP-induced cell death (p < 0.05). Our results revealed that BCL2A1 is a key gene for resistance during CHCP induced cell death. This resistance in TNBCs could be reversed with a combination of siRNA or BCL2A1 antagonist-CHCP therapy.
Definition of a Conserved Immunodominant Domain on Hepatitis C Virus E2 Glycoprotein by Neutralizing Human Monoclonal Antibodies (2008)

Development of a successful hepatitis C virus (HCV) vaccine requires the definition of neutralization epitopes that are conserved among different HCV genotypes. Five human monoclonal antibodies (HMAbs) are described that cross-compete with other antibodies to a cluster of overlapping epitopes, previously designated domain B. Each HMAb broadly neutralizes retroviral pseudotype particles expressing HCV E1 and E2 glycoproteins, as well as the infectious chimeric genotype 1a and genotype 2a viruses. Alanine substitutions of residues within a region of E2 involved in binding to CD81 showed that critical E2 contact residues involved in the binding of representative antibodies are identical to those involved in the binding of E2 to CD81.
Design of high efficiency polymeric cation exchange fibers1 (2001)

Abstract In this study, we have been exploring a new ion exchange material in the form of a fiber that could yield a number of important advantages over conventional ion exchange beads. In this approach, ion exchange fibers are prepared by 1) coating low‐cost glass fiber substrates with a polystyrene/divinylbenzene oligomer, 2) curing, and 3) sulfonating. The sulfonation process and effects of varying degrees of crosslinking were characterized through diffuse reflectance infrared spectroscopy and acid‐base neutralization titrations. Capacities of 4.7 meq/g (on a per resin basis) were easily obtained. Kinetics experiments showed the contact efficiencies of the new systems were greatly improved over the traditional beads due to greater surface associated with the film morphology and shorter diffusion lengths. This translated into an order of magnitude increase in ion exchange rate. As a result of the thin coatings, the use of solvents prior to functionalization, and preswelling of the finished product prior to end‐use were eliminated. Scanning electron microscopy was used to image the fibers and track­their mechanical integrity through various stages of­the process. Finally, repetitive regenerations proved­the long‐term stability of the spent fibers. Copyright­© 2001 John Wiley & Sons, Ltd.
An Electrically Using Alterable Nonvolatile Memory Cell a Floating-Gate Structure (1979)

An electrically alterable, floating-gate, nonvolatile memory transistor has been developed, with a cell area of under 500 Urn*, and using an advanced n-channel, polysilicon gate process. Cell program- ming occurs via hot-electron injection, exhibiting three distinct operating regimes. Erase, on the other hand, is based on field emission from floating gate to control gate. The magnitude of electrical erase is determined by applied bias, device parameters, and processing history, particularly the interlevel oxidation temperature. Analysis of experi- mental data shows that electrical erase does change programming characteristics significantly, and must be accounted for in circuit design. Memory retention, determined by thermal stress, is comparable to commercially available EPROM 's. The memory cell exhibits better than 1000-cycle write/erase capability, with degradation in interlevel conduction being the principal factor limiting endurance. A 5-V, 16K high-speed EAROM has been developed which shows successful programming and erase behavior at nominal voltages of 25 and 35 V, respectively.