gebhart/patrepeval huggingface dataset:
Targeting Undruggable Transcription Factors with PROTACs: Advances and Perspectives (2022)

Dysregulation of transcription factors has been implicated in a variety of human diseases. However, these proteins have traditionally been regarded as undruggable and only a handful of them have been successfully targeted by conventional small molecules. Moreover, the development of intrinsic and acquired resistance has hampered the clinical use of these agents. Over the past years, proteolysis-targeting chimeras (PROTACs) have shown great promise because of their potential for overcoming drug resistance and their ability to target previously undruggable proteins. Indeed, several small molecule-based PROTACs have demonstrated superior efficacy in therapy-resistant metastatic cancers. Nevertheless, it remains challenging to identify ligands for the majority of transcription factors. Given that transcription factors recognize short DNA motifs in a sequence-specific manner, multiple novel approaches exploit DNA motifs as warheads in PROTAC design for the degradation of aberrant transcription factors. These PROTACs pave the way for targeting undruggable transcription factors with potential therapeutic benefits.
Cluster Subanalysis of Patients With Severe Asthma Who Responded to Omalizumab (2021)

Statistical Methods-Study variablesThe variables included in the analysis were selected as per clinical criteria and statistical criteria (variables with many missing values were excluded).There was no control group.Therefore, it is a descriptive analysis in which no comparison between the different patient groups will be presented as per their treatment response but based on their pre-treatment baseline characteristics.Of the 345 evaluable patients from the FENOMA study, 89 were not included in the cluster analysis due to missing data.Thus, 256 patients (74%) served for cluster analysis.Descriptive statistics were calculated for demographic and clinical characteristics.Continuous variables are presented as median and quartile 1 (Q1) and quartile 3 (Q3).Categorical variables are reported by using frequency and percentage.For statistical comparisons, the following tests were used, as applicable: Kruskal-Wallis test, Chisquare test, Fisher's exact test, Wilcoxon signed-rank test, and t-test.A 2-tailed P value of less than 0.05 was used to denote statistically significant differences.All statistical analyses were performed with SAS version 9.4 and SAS Enterprise Guide V7.15 (SAS Institute, Cary, NC). Variable correlation analysisIn the case of highly correlated variable groups, a representative of each group is selected, as the information that these variables would provide to the analysis would be redundant, and it may
Parathyroid hormone receptors are plasma membrane glycoproteins with asparagine-linked oligosaccharides. (1988)

In the preceding article, we described physicochemical and kinetic properties of parathyroid hormone (PTH) receptors in clonal rat osteosarcoma cells (ROS 17/2.8) using photoaffinity ligand labeling and showed that the physiologically relevant receptor-ligand complex has an apparent Mr = 80,000. In this study, the photoaffinity labeled Mr = 80,000 receptor was localized exclusively on the cell surface plasma membrane and its glycoprotein nature was demonstrated through the use of lectin affinity-chromatography and specific exo- and endoglycosidases. Rinsing ROS cells, preincubated in the dark with 125I-labeled [Nle8, N-epsilon-(4-azido-2-nitrophenyl)Lys13,Nle18,Tyr34]bovine PTH-(1-34)-NH2 (NAP-NlePTH) (4 h, 15 degrees C, equilibrium conditions) with acidic phosphate-buffered saline (pH 2.5, 30 s, 4 degrees C) before photolysis resulted in selective and nearly total disappearance of the labeled Mr = 80,000 receptor. PTH receptor integrity to acid rinsing and photolysis was shown by relabeling the Mr = 80,000 receptor after a second incubation of these cells with 125I-labeled NAP-NlePTH, followed by photolysis. Adsorption of Triton X-100-solubilized, 125I-labeled NAP-NlePTH receptors to wheat germ agglutinin-agarose is nearly complete and highly selective, and elution with N-acetylglucosamine resulted in virtually total recovery of the labeled receptors from the column. The wheat germ agglutinin-retarded PTH receptors show increased electrophoretic mobility upon treatment with neuraminidase which was inhibited by simultaneous addition of 2,3-dehydro-3-desoxy-N-acetylneuraminic acid, a specific neuraminidase inhibitor. Endoglycosidase F treatment of the Mr = 80,000 receptors generated a single, labeled polypeptide with a Mr = 59,000 which migrated as a narrow band. PTH receptors on ROS 17/2.8 cells appear to be monomeric plasma membrane glycoproteins with an apparent Mr of 80,000 which contain a Mr = 59,000 polypeptide backbone and a polymeric arrangement of N-acetylglucosamine with N-acetylneuraminic acid as major terminal sugar residues.
Supplementary Table S1 from Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma (2023)

&lt;p&gt;Supplemental Table S1 Putative Metabolites&lt;/p&gt;
Optimal Home Energy Management Considering Uncertainties in Occupancy, Consumption, and Electricity Price (2022)

Power utilities issue demand response (DR) during the hours of peak load in order to reduce the demand on the network and provide congestion relief to overloaded circuits. While traditional residential DR programs are mainly one-way in the form of remote on/off control of air conditioning (A/C) units, residential customers can adopt a more proactive role through utilizing the capabilities of smart meters and home energy management systems (HEMS). HEMS can monitor energy rates and DR incentives, and accordingly change the temperature setpoint of the A/C unit and/or shift appliance loads from peak to off-peak hours in order to maximize financial benefits. All this can be achieved in an automated human-out-of-the-loop fashion. From the HEMS’ standpoint, the task can be viewed as solving an optimization problem with the goal of reducing power consumption while maximizing financial gains. However, another equally important goal would be to ensure that the comfort level of residents, if present in the building, is not compromised. This is especially crucial during periods of extreme temperatures where maintaining an acceptable indoor temperature has a direct impact on the residents’ health, especially children and the elderly. What makes this multi-objective optimization problem more challenging is the uncertain nature of some model parameters, e.g., electricity rates, building occupancy levels, and demand. This paper presents a novel solution for energy management of a smart home using DR by considering the above factors. To ensure that the solution found is feasible against all possible uncertainties, a robust model is developed and solved for a given time horizon. As shown through simulation results, considering uncertainties are necessary, since they can change the solution in a nonnegligible way.
Single crystalline cylindrical nanowires – toward dense 3D arrays of magnetic vortices (2016)

Magnetic vortex-based media have recently been proposed for several applications of nanotechnology; however, because lithography is typically used for their preparation, their low-cost, large-scale fabrication is a challenge. One solution may be to use arrays of densely packed cobalt nanowires that have been efficiently fabricated by electrodeposition. In this work, we present this type of nanoscale magnetic structures that can hold multiple stable magnetic vortex domains at remanence with different chiralities. The stable vortex state is observed in arrays of monocrystalline cobalt nanowires with diameters as small as 45 nm and lengths longer than 200 nm with vanishing magnetic cross talk between closely packed neighboring wires in the array. Lorentz microscopy, electron holography and magnetic force microscopy, supported by micromagnetic simulations, show that the structure of the vortex state can be adjusted by varying the aspect ratio of the nanowires. The data we present here introduce a route toward the concept of 3-dimensional vortex-based magnetic memories.
Immobilization of Proteins in their Physiological Active State at Functionalized Thiol Monolayers on ATR‐Germanium Crystals (2014)

Protein immobilization on solid surfaces has become a powerful tool for the investigation of protein function. Physiologically relevant molecular reaction mechanisms and interactions of proteins can be revealed with excellent signal-to-noise ratio by vibrational spectroscopy (ATR-FTIR) on germanium crystals. Protein immobilization by thiol chemistry is well-established on gold surfaces, for example, for surface plasmon resonance. Here, we combine features of both approaches: a germanium surface functionalized with different thiols to allow specific immobilization of various histidine-tagged proteins with over 99% specific binding. In addition to FTIR, the surfaces were characterized by XPS and fluorescence microscopy. Secondary-structure analysis and stimulus-induced difference spectroscopy confirmed protein activity at the atomic level, for example, physiological cation channel formation of Channelrhodopsin 2.
Effects of soybean lipoxygenase‐1 on phosphatidylcholines containing furan fatty acids (1994)

Naturally occurring tetraalkylsubstituted furan fatty acids (F-acids) were tested as potential substrates for soybean lipoxygenase-1. For this purpose, F-acid methyl ester and phosphatidylcholines containing F-acids at the sn-2 position of the glycerol residue were incubated with the enzyme. Oxidation of F-acids only occurs in the presence of linoleic acid as co-substrate. Linoleic acid is converted by lipoxygenase to the corresponding hydroperoxide that oxidizes the F-acid, probably in a radical reaction, to form an unstable dioxoene compound. This intermediate then forms, dependent on pH, unsaturated furanoid acids or isomers with cyclopentenolone structure that can be detected by gas chromatography/mass spectrometry (GC/MS). F-acids located at the sn-2 position of a synthetic phosphatidylcholine (PC), containing linoleic acid in the sn-1 position, are co-oxidized to a greater extent by incubation with soybean lipoxygenase-1 than are F-acids bound to PC with myristic acid in the sn-1 position when subjected to the enzyme in the presence of a great excess of linoleic acid. The results suggest that F-acids may play a strategic role in antioxidative processes in plant cells.
A High speed, Low Voltage to High Voltage Level Shifter in Standard 1.2V 0.13&#x003BC;m CMOS (2006)

The design of a high speed, low voltage to high voltage level shifter in a digital 1.2 V, 0.13 mum CMOS technology is presented. The topology uses two differentially switched cascoded transistor ladders. The output signal has an offset of two times the nominal supply voltage of the used technology with respect to the input signal. Oxide stress and hot carrier degradation is minimized since all transistors of the level shifter operate within the voltage limits imposed by the design rules of a mainstream CMOS technology.
Human newborns match tongue protrusion of disembodied human and robotic mouths (2010)

No evidence had been provided so far of newborns’ capacity to give a matching response to 2D stimuli. We report evidence from 18 newborns who were presented with three types of stimuli on a 2D screen. The stimuli were video-recorded displays of tongue protrusion shown by: (a) a human face, (b) a human tongue from a disembodied mouth, and (c) an artificial tongue from a robotic mouth. Compared to a baseline condition, neonates increased significantly their tongue protrusion when seeing disembodied human and artificial tongue movements, but not when seeing a 2D full-face protruding tongue. This result was interpreted as revealing the exploration of top-heavy patterns of the 2D face that distracted infants’ attention from the tongue. Results also showed progressively more accurate matching (full tongue protrusion) throughout repeated exposure to each kind of stimulus. Such findings are not in line with the predictions of the innate releasing mechanism (IRM) model or of the oral exploration hypothesis. They support the active intermodal mapping (AIM) hypothesis that emphasizes not only the importance of repeated experience, as would the associative sequence learning (ASL) hypothesis, but also predicts a differential learning and progressive correction of the response adapted to each stimulus.
Analysis of the Carbon and Nitrogen Limitations to Soybean Yield1 (1976)

Abstract Soybeans are hypothesized to be “self‐destructive” since they apparently need to translocate large amounts of nitrogen from vegetative tissues during seed‐fill to sustain seed growth. To assess the possible limitations of this characteristic on soybean seed yield, a simple, dynamic simulation model is developed which accounts for the availability of nitrogen and photosynthate within the plant. The simulations show that the duration of seedfill and seed yield is clearly limited by the self‐destructive characteristic. Increased availability of nitrogen within the plant is required for significant increases in soybean yields. Possible alterations of the model required to mimic actual soybean seed growth are presented.
A survey on OLAP (2016)

Online analytical processing is to-days major database technology that has completely changed the face of decision support systems. Many of the enterprise real-time analytical solutions are provided using most advanced OLAP methods. In this paper, we have presented the overview of the various OLAP technologies and their access paths. The focus of this paper is on OLAP in distributed scenario, where we pinned on the drawback of OLAPs natural indexing search. We designed a new translated lattice called the pchrome lattice, whose nodes are binary. We implemented the natural indexing on this translated lattice and showed a drastic reduce in indexing search space, search time and distributed communication cost.
A new ZVS-PWM full-bridge converter (2003)

A full-bridge converter which employs a coupled inductor to achieve zero-voltage switching of the primary switches in the entire line and load range is described. Because the coupled inductor does not appear as a series inductance in the load current path, it does not cause a loss of duty cycle or severe voltage ringing across the output rectifier. The operation and performance of the proposed converter is verified on a 670 W prototype.
Residual Splash for Optimally Parallelizing Belief Propagation (2009)

As computer architectures move towards multicore we must build a theoretical understanding of parallelism in machine learning. In this paper we focus on parallel inference in graphical models. We demonstrate that the natural, fully synchronous parallelization of belief propagation is highly inefficient. By bounding the achievable parallel performance in chain graphical models we develop a theoretical understanding of the parallel limitations of belief propagation. We then provide a new parallel belief propagation algorithm which achieves optimal performance. Using two challenging real-world tasks, we empirically evaluate the performance of our algorithm on large cyclic graphical models where we achieve near linear parallel scaling and out perform alternative algorithms. 1
Chemical constituents, cytotoxic and antioxidant activities of extract from the rhizomes of Osmunda japonica Thunb (2018)

Thirty-three compounds (<b>1</b>-<b>33</b>) were isolated from the rhizomes of <i>Osmunda japonica</i>. Their structures were elucidated on the basis of spectral analysis and identified as <i>ent</i>-kaurene terpenoids (1-3), anthraquinones (4-8), flavonoids (9-12), steroids (13-15), and other compounds (<b>16</b>-<b>33</b>). Compound <b>1</b>-<b>14</b>, <b>19</b>-<b>27</b> were isolated from the genus osmunda for the first time. Compound <b>28-29</b> were isolated from the plant for the first time. Cytotoxicities of all compounds against Hela, HepG2 and A549 cell lines were measured by MTT assay, and their antioxidant activities were determined by DPPH and ABTS radical scavenging assays. Compound <b>2</b> exhibited potent cytotoxicity against Hela, HepG2 cell lines with IC<sub>50</sub> values of 9.31 and 9.66 μM, respectively. Compound <b>9</b> showed good antioxidant activity. The Trolox-equivalent antioxidant capacity (TEAC) value was 0.95 mM in ABTS assay, and the IC<sub>50</sub> value was 18.63 μM in DPPH assay.
ChemInform Abstract: Chemistry of N‐Heterocyclic Sulfur Compounds. Reaction of 2,5‐Dimercapto‐1,3,4‐thiadiazoles with 1,ω‐Dibromoalkanes. Synthesis of Tetrathia‐((n + 2).(n + 2))(2,5)‐1,3,4‐thiadiazolophanes and Dithia‐((n + 1).(n + 1))(3,5)‐1,3,4‐thiadiazolinophanedithiones. (1987)

Abstract Reaction of the dimercaptothiadiazole (I) with the dibromoalkanes (II) gives certain products due to heterocyclization both via S,S‐(III) and via N,S‐(IV).
An electron-rich olefin as a source of co-ordinated carbene; synthesis of trans-PtCl2[C(NPhCH2)2]PEt3 (1971)

Interaction of the appropriate electron-rich olefin and chloride bridged PtII dimer has yielded the unreactive trans-PtII carbene complex (I) which is belived to isomerise thermally to the cis-isomer; the structure of the trans-complex is established inter alia by a single crystal X-ray analysis.
Volatile Compounds Analysis of Tunisian Propolis and Its Antifungal Activity (2018)

In this study, four samples of Tunisian propolis were analyzed for their volatile compounds. Static Headspace technique coupled with gas chromatography-mass spectrometry (GC/MS) was used for the volatile profile characterization. Statistical investigation of the samples was made applying hierarchical clustering method, K-Means cluster and principal component analysis. Results showed that 47, 36, 30 and 24 different compounds were identified, respectively, in the samples from Zouarine, Zelligua, Bizerte and Beni Khalled. Propolis volatiles were dominated by monoterpene hydrocarbons. α-pinene was the major compound representing 81.14%, 82.67% and 90.74%, respectively, of the total propolis volatiles collected from Zelligua, Beni Khalled and Zouarine and only 45.22% of the sample from Bizerte which had a very different composition. The in vitro antifungal activity of the volatiles from all samples against Candida albicans was also assayed and reported.
<title>Silicon Position Sensing Detectors For Precision Measurement And Control</title> (1978)

This paper examines the use of speciallized silicon detectors in position and angle measurement systems. The operational characteristics of segmented position sensors are compared with those of lateral cell position sensors. Segmented position sensors of the quadrant and bi-cell variety exhibit the greater position sensitivity and resolution but have dynamic operating ranges which are limited to the dimensions of the optical image focused onto the detector. Segmented cells require uniform illumination intensity in the spot to achieve good linearity. They can operate at bandwidths of well over 100 megahertz as may be required in pulsed and high-speed tracking applications. Lateral cells are available in single and dual axis con-figurations. Their dynamic operating range is independent of spot size (excluding edge obscuration effects). Linearity and absolute measurement accuracy is also independent of spot size and uniformity characteristics to first order. Other advantages include excellent linearity, large operating range, and electronically adjustable null. Angle, x-y displacement and z-axis measuring schemes are discussed and two in-process measuring systems using lateral cells are described: an electronic auto-collimator for measuring tappet bore angles and an automatic &quot;seam tracker&quot; used to guide a TIG welding head.
Solid-Phase Peptide Synthesis Using Microwave Irradiation (2011)

Since the advent of solid-phase peptide synthesis (SPPS) in the late 1950s, numerous advancements in the underlying chemistry (i.e., orthogonal protection strategy, coupling reagents, and solid support matrices) have greatly improved the efficiency of the technique. More recently, application of microwave radiation to SPPS has been found to reduce reaction time and/or increase the initial purity of synthetic peptide products. In this protocol, conditions are described to accomplish rapid peptide coupling and 9-fluorenylmethoxycarbonyl (Fmoc) removal reactions under temperature-controlled conditions in either a manual or automated synthesis format using a microwave reactor. These microwave-assisted peptide synthesis procedures have been used to rapidly prepare a "difficult" peptide sequence from the acyl carrier protein, ACP(65-74), in less than 3 h and the reduced, linear precursor to human hepcidin, in high initial purity.
Pentachlorphenol migration from treated wood exposed to simulated rainfall (2008)

Abstract The leaching of toxins from treated wood poses an, as yet, poorly quantified risk to both plant and animal life. In particular, the leaching of pentachlorophenol (PCP) into rainwater falling on treated wood over aquatic environments, such as bridges, is understudied. Computer models have been developed which predict the leaching of creosote from marine pilings. If data were available, similar models could be developed for PCP-treated bridges and the risk to waterways determined for various structural designs. Providing such data is the objective of this study, where the migration of PCP from treated wood under the influence of simulated rainfall was studied using a simulation system that delivered uniform rainfall rates over-treated wood. The runoff from the treated wood was captured and analyzed with high resolution gas chromatography combined with low resolution mass spectrometry. PCP migrated from treated wood into rainwater runoff at a fairly constant rate of approximately 0.15 g l -1 m -2 . Small non-significant deviations were observed with rainfall rate, time, and temperature. We suggest that PCP migration rates from exposed treated wood can be modeled and thereby predict the migration of PCP from this source into the environment.
Roll-Tilt Perception Using a Somatosensory Bar Task (1999)

Visual estimates of roll-tilt perception during static roll-tilt are confounded by an offset due to the ocular counterroll that simultaneously occurs. An alternative, non-visual ('somatosensory') measure of roll-tilt perception was developed which is not contaminated by this offset. The aims of this study were to determine: 1) inter-subject variability of somatosensory settings across test session in normal subjects and patients with unilateral or bilateral vestibular loss and 2) intra-subject variability of settings across test session in normal subjects.
Single‐nucleotide polymorphism analysis using fluorescence resonance energy transfer between DNA‐labeling fluorophore, fluorescein isothiocyanate, and DNA intercalator, POPO‐3, on bacterial magnetic particles (2003)

To develop an analytical system for single-nucleotide polymorphisms (SNPs), the fluorescence resonance energy transfer (FRET) technique was employed on a bacterial magnetic particle (BMP) surface. A combination of fluorescein isothiocyanate (FITC; excitation 490 nm/emission 520 nm) labeled at the 5' end of DNA and an intercalating compound (POPO-3, excitation 534 nm/emission 570 nm) was used to avoid the interference from light scattering caused by nanoparticles. After hybridization between target DNA immobilized onto BMPs and FITC-labeled probes, fluorescence from POPO-3, which was excited by the energy from the FITC, was detected. The major homozygous (ALDH2*1), heterozygous (ALDH2*1/*2), and minor homozygous (ALDH2*2) genotypes in the blood samples were discriminated by this method. The assay described herein allows for a simple and rapid SNP analysis using a fully automated system.
Adenoviral-mediated gene transfer to murine small intestine is more efficient in neonates than adults (1997)

Gene transfer to neonatal and adult small intestine is feasible using recombinant adenovirus and is more efficient in neonates as indicated by increased surface area of marker gene expression, effectiveness of intraperitoneal delivery, and the ability to readminister recombinant adenovirus.