gebhart/patrepeval huggingface dataset:
Functional antagonism between RNA polymerase II holoenzyme and global negative regulator NC2   <i>in vivo</i> (1997)

Activation of eukaryotic class II gene expression involves the formation of a transcription initiation complex that includes RNA polymerase II, general transcription factors, and SRB components of the holoenzyme. Negative regulators of transcription have been described, but it is not clear whether any are general repressors of class II genes in vivo. We reasoned that defects in truly global negative regulators should compensate for deficiencies in SRB4 because SRB4 plays a positive role in holoenzyme function. Genetic experiments reveal that this is indeed the case: a defect in the yeast homologue of the human negative regulator NC2 (Dr1 x DRAP1) suppresses a mutation in SRB4. Global defects in mRNA synthesis caused by the defective yeast holoenzyme are alleviated by the NC2 suppressing mutation in vivo, indicating that yeast NC2 is a global negative regulator of class II transcription. These results imply that relief from repression at class II promoters is a general feature of gene activation in vivo.
Model Predictive Control for Central Plant Optimization with Thermal Energy Storage (2014)

An optimization framework is used in order to determine how to distribute both hot and cold water loads across a central energy plant including heat pump chillers, conventional chillers, water heaters, and hot and cold water (thermal energy) storage. The objective of the optimization framework is to minimize cost in response to both real-time energy prices and demand charges. The linear programming framework used allows for the optimal solution to be found in real-time. Real-time optimization lead to two separate applications: A planning tool and a real-time optimization tool. In the planning tool the optimization is performed repeatedly with a sliding horizon accepting a subset of the optimized distribution trajectory horizon as each subsequent optimization problem is solved. This is the same strategy as model predictive control except that in the design and planning tool the optimization is working on a given set of loads, weather (e.g. TMY data), and real-time pricing data and does not need to predict these values. By choosing the varying lengths of the horizon (2 to 10 days) and size of the accepted subset (1 to 24 hours), the design and planning tool can be used to find the design year’s optimal distribution trajectory in less than 5 minutes for interactive plant design, or the design and planning tool can perform a high fidelity run in a few hours. The fast solution times also allow for the optimization framework to be used in real-time to optimize the load distribution of an operational central plant using a desktop computer or microcontroller in an onsite Enterprise controller. In the real-time optimization tool Model Predictive Control is used; estimation, prediction, and optimization are performed to find the optimal distribution of loads for duration of the horizon in the presence of disturbances. The first distribution trajectory in the horizon is then applied to the central energy plant and the estimation, prediction, and optimization is repeated in 15 minutes using new plant telemetry and forecasts. Prediction is performed using a deterministic plus stochastic model where the deterministic portion of the model is a simplified system representing the load of all buildings connected to the central energy plant and the stochastic model is used to respond to disturbances in the load. The deterministic system uses forecasted weather, time of day, and day type in order to determine a predicted load. The estimator uses past data to determine the current state of the stochastic model; the current state is then projected forward and added to the deterministic system’s projection. In simulation, the system has demonstrated more than 10% savings over other schedule based control trajectories even when the subplants are assumed to be running optimally in both cases (i.e., optimal chiller staging, etc.). For large plants this can mean savings of more than US $1 million per year.
Parenteral dosage form development and testing of dimethyl trisulfide, as an antidote candidate to combat cyanide intoxication (2016)

This study focused on the solubility enhancement and the in vivo antidotal efficacy testing of a new potential cyanide (CN) countermeasure, dimethyl trisulfide (DMTS). Various FDA approved cyclodextrins (HPβCD, RMβCD, HPγCD), cosolvents (ethanol, polyethylene glycols, propylene glycol), surfactants (cremophor EL, cremophor RH 40, sodium cholate, sodium deoxycholate, polysorbate 80) and their combinations were applied. Based on the solubility enhancing potential of the tested systems, polysorbate 80 was chosen for further in vivo efficacy studies. A composition comprising 15% polysorbate 80 and 50 mg/ml DMTS with the applied DMTS dose of 100 mg/kg provided a therapeutic antidotal protection of 3.4 × LD<sub>50</sub>. For comparison, the present therapy of sodium thiosulfate (TS) with the dose of 100 mg/kg provided only 1.1 × LD<sub>50</sub> protection, and at the dose of 200 mg/kg, the LD<sub>50</sub> was enhanced by 1.3 times. No difference in the therapeutic protection by DMTS was detected when the concentration of polysorbate 80 was increased to 20% (3.2 × LD<sub>50</sub> protection). These data demonstrate the potential importance of DMTS as a CN countermeasure, and the formulation comprising polysorbate 80 provides the base of an injectable intramuscular dosage form that can later serve as a CN antidotal kit suitable for mass scenario.
Development of a direct contact astrocyte-human cerebral microvessel endothelial cells blood–brain barrier coculture model (2017)

Paracellular permeability reductions with the direct coculture system may enhance therapeutic agent and potential neurotoxicant screening for BBB permeability better than the currently available monoculture and indirect coculture in-vitro models.
Opioid and melanocortin receptors: Do they have overlapping pharmacophores? (2007)

We have identified compound 1 as a novel ligand for opioid and melanocortin (MC) receptors, which is derived from the overlapping of a well known structure for the delta opioid receptor, 2,6-dimethyltyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), and a small molecule for the MC receptor, Tic-DPhe(p-Cl)-piperidin-4-yl-N-phenyl-propionamide. Ligand 1 showed that there is an overlapping pharmacophore between opioid and MC receptors through the Tic residue. The ligand displayed high biological activities at the delta opioid receptor (Ki = 0.38 nM in binding assay, EC(50) = 0.48 nM in GTP-gamma-S binding assay, IC(50) = 74 nM in MVD) as an agonist instead of an antagonist and showed selective binding affinity (IC(50) = 2.3 muM) at the MC-3 receptor rather than at the MC-5 receptor. A study of the structure-activity relationships demonstrated that the residues in positions 2, 3, and the C-terminus act as a pharmacophore for the MC receptors, and the residues in positions 1 and 2 act as a pharmacophore for the opioid receptors. Thus, this structural construct can be used to prepare chimeric structures with adjacent or overlapping pharmacophores for opioid and MC receptors.
Single-Cell Tracking With PET Using a Novel Trajectory Reconstruction Algorithm (2014)

Virtually all biomedical applications of positron emission tomography (PET) use images to represent the distribution of a radiotracer. However, PET is increasingly used in cell tracking applications, for which the "imaging" paradigm may not be optimal. Here, we investigate an alternative approach, which consists in reconstructing the time-varying position of individual radiolabeled cells directly from PET measurements. As a proof of concept, we formulate a new algorithm for reconstructing the trajectory of one single moving cell directly from list-mode PET data. We model the trajectory as a 3-D B-spline function of the temporal variable and use nonlinear optimization to minimize the mean-square distance between the trajectory and the recorded list-mode coincidence events. Using Monte Carlo simulations (GATE), we show that this new algorithm can track a single source moving within a small-animal PET system with 3 mm accuracy provided that the activity of the cell [Bq] is greater than four times its velocity [mm/s]. The algorithm outperforms conventional ML-EM as well as the "minimum distance" method used for positron emission particle tracking (PEPT). The new method was also successfully validated using experimentally acquired PET data. In conclusion, we demonstrated the feasibility of a new method for tracking a single moving cell directly from PET list-mode data, at the whole-body level, for physiologically relevant activities and velocities.
TRIFUNCTIONAL LIGANDS: A RADIOIODINATED HIGH AFFINITY ACYLATING ANTAGONIST FOR THE A<sub>1</sub> ADENOSINE RECEPTOR. (1992)

A new xanthine (adenosine antagonist) radioligand that binds covalently to A<sub>1-</sub>adenosine receptors was prepared and used as a receptor probe. BH-DITC-XAC was synthesized via a trifunctional aryl diisothiocyanate crosslinker. containing the p-hydroxyphenylpropionyl group for radioiodination. The xanthine competed against agonist or antagonist A<sub>1</sub> receptor radioligands in bovine brain membranes with an IC<sub>50</sub>, of 40nM. <sup>125</sup>I-BH-DITC-XAC, prepared directly by the chloramine T method and purified by HPLC. bound specifically to A<sub>1</sub> receptors. This binding was inhibited in the presence of the adenosine agonists <i>R</i>-PIA, <i>S</i>-PIA. and NECA in a dose dependent manner and with the order of potency characteristic of bovine A<sub>1</sub> receptors. Incubation of affinity purified bovine A<sub>1</sub>-receptors with <sup>125</sup>I-BH-DITC-XAC (0.8 nM) for 2 hours resulted in the specific and clean labelling of a polypeptide band corresponding to MW 36,000, identical to that previously found for the A<sub>1</sub> receptor.
Immunoglobulin V <sub>H</sub> 3 Gene Products: Natural Ligands for HIV gp120 (1993)

Infection with human immunodeficiency virus-type 1 (HIV-1) depletes T cells expressing CD4 and B cells expressing immunoglobulin (Ig) VH3 gene products. A subpopulation of normal B cells from non-HIV-infected individuals was shown to bind to HIV gp120 by means of membrane Ig; most of these B cells expressed VH3 family Ig. Serum VH3 IgM from uninfected individuals also avidly bound gp120. Finally, gp120 selectively induced Ig secretion by VH3 B cells, indicating that the binding of gp120 functionally activated these cells. These results indicate that naturally occurring VH3 Ig is a second ligand for gp120 and a candidate superantigen for VH3 B cells.
Ionic Liquid Pretreatment of Poplar Wood at Room Temperature: Swelling and Incorporation of Nanoparticles (2010)

Lignocellulosic biomass offers economic and environmental advantages over corn starch for biofuels production. However, its fractionation currently requires energy-intensive pretreatments, due to the lignin chemical resistance and complex cell wall structure. Recently, ionic liquids have been used to dissolve biomass at high temperatures. In this study, thin sections of poplar wood were swollen by ionic liquid (1-ethyl-3-methylimidazolium acetate) pretreatment at room temperature. The samples contract when rinsed with deionized water. The controlled expansion and contraction of the wood structure can be used to incorporate enzymes and catalysts deep into the wood structure for improved pretreatments and accelerated cellulose hydrolysis. As a proof of concept, silver and gold nanoparticles of diameters ranging from 20 to 100 nm were incorporated at depths up to 4 mum. Confocal surface-enhanced Raman images at different depths show that a significant number of nanoparticles were incorporated into the pretreated sample, and they remained on the samples after rinsing. Quantitative X-ray fluorescence microanalyses indicate that the majority of nanoparticle incorporation occurs after an ionic liquid pretreatment of less than 1 h. In addition to improved pretreatments, the incorporation of materials and chemicals into wood and paper products enables isotope tracing, development of new sensing, and imaging capabilities.
Rotating Electrode Potentiometry:  Lowering the Detection Limits of Nonequilibrium Polyion-Sensitive Membrane Electrodes (2000)

A rotating electrode configuration is evaluated as a means to lower the detection limits of newly devised polyion-sensitive membrane electrodes (PSEs). Planar potentiometric polycation and polyanion PSEs are prepared by incorporating tridodecylmethylammonium chloride and calcium dinonylnaphthalenesulfonate, respectively, into plasticized PVC or polyurethane membranes and mounting disks of such films on an electrode body housed in a conventional rotating disk electrode apparatus. Rotation of the PSEs at 5000 rpm results in an enhancement in the detection limits toward heparin (polyanion) and protamine (polycation) of at least 1 order of magnitude (to 0.01 unit/mL for heparin; 0.02 microg/mL for protamine) over that observed when the EMF responses of the same electrodes are assessed using a stir-bar to achieve convective mass transport. A linear relationship between omega(-1/2), where omega is the rotating angular frequency, and C1/2, the polyion concentration corresponding to half the total maximum deltaEMF response toward the polyion species, is observed. It is further shown that the rotating polycation sensor can be used as an end-point detector to greatly enhance (relative to nonrotated indicator electrode) the analytical resolution and precision for measurement of low concentrations of heparin when such samples are titrated with protamine. The theoretical basis for lowering the detection limits by rotating PSEs is discussed based on the unique nonequilibrium response mechanism of such sensors.
Hydrogel Microencapsulated Insulin-Secreting Cells Increase Keratinocyte Migration, Epidermal Thickness, Collagen Fiber Density, and Wound Closure in a Diabetic Mouse Model of Wound Healing (2015)

Wound healing is a hierarchical process of intracellular and intercellular signaling. Insulin is a potent chemoattractant and mitogen for cells involved in wound healing. Insulin's potential to promote keratinocyte growth and stimulate collagen synthesis in fibroblasts is well described. However, there currently lacks an appropriate delivery mechanism capable of consistently supplying a wound environment with insulin; current approaches require repeated applications of insulin, which increase the chances of infecting the wound. In this study, we present a novel cell-based therapy that delivers insulin to the wound area in a constant or glucose-dependent manner by encapsulating insulin-secreting cells in nonimmunogenic poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We evaluated cell viability and insulin secretory characteristics of microencapsulated cells. Glucose stimulation studies verified free diffusion of glucose and insulin through the microspheres, while no statistical difference in insulin secretion was observed between cells in microspheres and cells in monolayers. Scratch assays demonstrated accelerated keratinocyte migration in vitro when treated with microencapsulated cells. In excisional wounds on the dorsa of diabetic mice, microencapsulated RIN-m cells accelerated wound closure by postoperative day 7; a statistically significant increase over AtT-20ins-treated and control groups. Histological results indicated significantly greater epidermal thickness in both microencapsulated RIN-m and AtT-20ins-treated wounds. The results suggest that microencapsulation enables insulin-secreting cells to persist long enough at the wound site for a therapeutic effect and thereby functions as an effective delivery vehicle to accelerate wound healing.
A Bottle-around-a-Ship Method To Generate Hollow Thin-Shelled Particles Containing Encapsulated Iron Species with Application to the Environmental Decontamination of Chlorinated Compounds (2018)

Thin-shelled hollow silica particles are synthesized using an aerosol-based process where the concentration of a silica precursor tetraethyl orthosilicate (TEOS) determines the shell thickness. The synthesis involves a novel concept of the salt bridging of an iron salt, FeCl<sub>3</sub>, to a cationic surfactant, cetyltrimethylammonium bromide (CTAB), which modulates the templating effect of the surfactant on silica porosity. The salt bridging leads to a sequestration of the surfactant in the interior of the droplet with the formation of a dense silica shell around the organic material. Subsequent calcination consistently results in hollow particles with encapsulated iron oxides. Control of the TEOS levels leads to the generation of ultrathin-shelled (∼10 nm) particles which become susceptible to rupture upon exposure to ultrasound. The dense silica shell that is formed is impervious to entry of chemical species. Mesoporosity is restored to the shell through desilication and reassembly, again using CTAB as a template. The mesoporous-shelled hollow particles show good reactivity toward the reductive dichlorination of trichloroethylene (TCE), indicating access of TCE to the particle interior. The ordered mesoporous thin-shelled particles containing active iron species are viable systems for chemical reaction and catalysis.
Nonparametric model-based prognostics (2008)

Equipment, process, and system prognostic techniques can be classified as belonging to one of three major classes of methods: 1) conventional reliability-based using failure times (Weibull), 2) population based with environmental considerations (e.g. proportional hazards modeling), and 3) individual based (e.g. general path model). A new individual-based prognostic algorithm, termed the path classification and estimation (PACE) model, has been developed and is based entirely on failure data. This model recasts the general path model (GPM), which is the foundation of the majority of the modern individual based prognosis algorithms, as a classification problem, where a current device's degradation path is classified according to a series of exemplar paths and the results of the classification are used to estimate the remaining useful life (RUL) of the device. The requirement of the existence of a failure threshold is removed, thereby enabling the PACE to be applied to ldquoreal worldrdquo systems, where a single failure threshold is not likely to occur. If the failure threshold is known, simple formatting may be applied to the degradation paths such that they can be easily used with the PACE. The newly proposed method was applied to data collected from the hydraulic steering system of a drill used for deep oil exploration with the objective of detecting, diagnosing, and prognosing faults. The PACE was used to predict the RUL for several failure modes using actual data. For this work, a three tiered architecture was implemented, where conventional reliability methods were used to estimate the population-based RUL, PACE population-based prognosers were trained to map the cause of a failure mode to the RUL, and PACE individual prognosers were trained to map the effects of a failure mode to the RUL. It was found that the population based prognoser produced RUL estimates with large errors (75 hours) and uncertainties (261 hours). The individual prognosers were found to significantly outperform the population based prognoser, with errors ranging from 1.2 to 11.4 hours with 95% confidence intervals ranging from 0.67 to 32.02 hours.
Acute Ablation of Cortical Pericytes Leads to Rapid Neurovascular Uncoupling (2020)

Pericytes are perivascular mural cells that enwrap brain capillaries and maintain blood-brain barrier (BBB) integrity. Most studies suggest that pericytes regulate cerebral blood flow (CBF) and oxygen delivery to activated brain structures, known as neurovascular coupling. While we have previously shown that congenital loss of pericytes leads over time to aberrant hemodynamic responses, the effects of acute global pericyte loss on neurovascular coupling have not been studied. To address this, we used our recently reported inducible pericyte-specific Cre mouse line crossed to iDTR mice carrying Cre-dependent human diphtheria toxin (DT) receptor, which upon DT treatment leads to acute pericyte ablation. As expected, DT led to rapid progressive loss of pericyte coverage of cortical capillaries up to 50% at 3 days post-DT, which correlated with approximately 50% reductions in stimulus-induced CBF responses measured with laser doppler flowmetry (LDF) and/or intrinsic optical signal (IOS) imaging. Endothelial response to acetylcholine, microvascular density, and neuronal evoked membrane potential responses remained, however, unchanged, as well as arteriolar smooth muscle cell (SMC) coverage and functional responses to adenosine, as we previously reported. Together, these data suggest that neurovascular uncoupling in this model is driven by pericyte loss, but not other vascular deficits or neuronal dysfunction. These results further support the role of pericytes in CBF regulation and may have implications for neurological conditions associated with rapid pericyte loss such as hypoperfusion and stroke, as well as conditions where the exact time course of global regional pericyte loss is less clear, such as Alzheimer's disease (AD) and other neurogenerative disorders.
High-Speed Nested Cascaded MASH Digital Delta-Sigma Modulator-Based Divider Controller (2018)

The MASH Digital Delta-Sigma Modulator (DDSM) based divider controller represents a speed bottleneck in state of the art commercial PLL-based fractional-N frequency synthesizers. As next generation systems require higher phase detector frequencies, there is a need to make ever faster divider controllers. This paper describes a fine-grained nested cascaded MASH DDSM which is significantly faster than state of the art divider controllers, thereby eliminating the current speed bottleneck.
A 160 µA, 8 mdps/<inf>√</inf>Hz frequency-modulated MEMS yaw gyroscope (2017)

This paper presents a frequency-modulated (FM), consumer-grade yaw-rate sensor. The system consists of a custom low-power (160 μA), low-phase-noise (-135 dBc/Hz at 100 Hz offset) integrated circuit (IC), coupled to a novel (930 μm) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> z-axis MEMS sensor fabricated in a 24-μm-thick industrial process. In operation, it shows a ratiometric scale factor of 1.6 Hz/Hz, and a white noise of 8 mdps/√Hz, both independent of process nonuniformities.
Enhanced detection of type C botulinum neurotoxin by the Endopep-MS assay through optimization of peptide substrates (2015)

It is essential to have a simple, quick and sensitive method for the detection and quantification of botulinum neurotoxins, the most toxic substances and the causative agents of botulism. Type C botulinum neurotoxin (BoNT/C) represents one of the seven members of distinctive BoNT serotypes (A to G) that cause botulism in animals and avians. Here we report the development of optimized peptide substrates for improving the detection of BoNT/C and /CD mosaic toxins using an Endopep-MS assay, a mass spectrometry-based method that is able to rapidly and sensitively detect and differentiate all types of BoNTs by extracting the toxin with specific antibodies and detecting the unique cleavage products of peptide substrates. Based on the sequence of a short SNAP-25 peptide, we conducted optimization through a comprehensive process including length determination, terminal modification, single and multiple amino acid residue substitution, and incorporation of unnatural amino acid residues. Our data demonstrate that an optimal peptide provides a more than 200-fold improvement over the substrate currently used in the Endopep-MS assay for the detection of BoNT/C1 and /CD mosaic. Using the new substrate in a four-hour cleavage reaction, the limit of detection for the BoNT/C1 complex spiked in buffer, serum and milk samples was determined to be 0.5, 0.5 and 1mouseLD50/mL, respectively, representing a similar or higher sensitivity than that obtained by traditional mouse bioassay.