gebhart/patrepeval huggingface dataset:
Thyroid Hormone Regulation of miR-21 Enhances Migration and Invasion of Hepatoma (2013)

Thyroid hormone (T(3)) signaling through the thyroid hormone receptor (TRα1) regulates hepatoma cell growth and pathophysiology, but the underlying mechanisms are unclear at present. Here, we have shown that the oncomir microRNA-21 (miR-21) is activated by T(3) through a native T(3) response element in the primary miR-21 promoter. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T(3) stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T(3). The Rac-controlled regulator of invasion and metastasis, T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally downregulated by T(3). Attenuation and overexpression of miR-21 induced upregulation and downregulation of TIAM1, respectively. TIAM1 attenuation, in turn, enhanced migration and invasion via the upregulation of β-catenin, vimentin, and matrix metalloproteinase-2 in hepatoma cells. Notably, correlations between TRα1, miR-21, and TIAM1 expression patterns in animal models paralleled those observed in vitro. In the clinic, we observed a positive correlation (P = 0.005) between the tumor/nontumor ratios of TRα1 and miR-21 expression, whereas a negative correlation (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma. Our findings collectively indicate that miR-21 stimulation by T(3) and subsequent TIAM1 suppression promotes hepatoma cell migration and invasion.
Homing and Engraftment of Bone Marrow Derived Cells in Irradiated Mouse Lungs. (2009)

Abstract Abstract 4600 To determine the degree to which murine bone marrow migrates to and can repopulate damaged lung, we studied lung stem cell expression of the Clara Cell Specific Protein (CCSP). Several different models have been used to deplete the lung stem cells. We used CCtk mice which expresses the HSV-tk under control of the CCSP promoter. Subcutaneous administration of gancicylovir (50 mg/ml) over a 7 day period using Alzet osmotic pumps results in the reduction of CCSP RNA and CCSP positive cells. To determine if a reduced dose of gancicylovir reduced CCSP cells to a nonfatal degree and opened a stem cell niche for homing of hematopoietic cells, CCtk mice had osmotic pumps placed subcutaneously containing a lower dose of 25 mg/ml of gancicylovir. The lungs were explanted at serial times up to 7 days after pump placement. RNA was extracted and real time polymerase chain reaction (RT-PCR) using primers specific for CCSP was used to quantitate CCSP expression. CCtk mice treated with gancicylovir showed a 70% reduction of lung CCSP expression. CCtk mice implanted with osmotic pumps containing 25 mg/ml gangcicylovir and injected intravenously with bone marrow from sex-mismatched GFP+ transgenic FVB male mouse 2 days later were followed for thirty days. The mice were sacrificed, lungs removed, single cell suspensions prepared, stained with a PE labeled anti-CD45 monoclonal antibody and analyzed by flow cytometry for GFP positive, CD45 negative cells. No GFP+, CCSP+ cells cells were detected. Injection of FVB mice with naphthalene (which kills differentiated but not stem CCSP+ cells) at 200 mg/kg intraperitoneally resulted in an 87% decrease in CCSP expression. When injected with bone marrow cells from GFP+ transgenic mice at serial times to 7 days and sacrificed at day 30, again no GFP+ CCSP+ cells were identified. In a third attempt to remove additional CCSP cells and prepare sites for homing of marrow cells, FVB mice were treated with naphthalene (200 mg/kg) followed by 20 Gy irradiation to the lungs 48 hr later, then injected with GFP+ bone marrow, 24 hr later. The mice were sacrificed 30 days later, and examined for GFP+, CD45- cells. Low numbers of GFP+ CCSP+ cells were detected. The data indicates a low baseline level of hematopoietic stem cell potential to home and differentiate to CCSP positive lung cells. Supported by NIH-2R01CA119927-08A1. Disclosures: No relevant conflicts of interest to declare.
Utilizing Production Viable Valve Strategies at Elevated Speeds and Loads to Improve Volumetric Efficiency via Intake Valve Modulation (2018)

Valvetrain flexibility enables the optimization of the engine’s ability to breathe across the operating range, resulting in more efficient operation. The authors have shown the merit of improving volumetric efficiency via valvetrain flexibility to improve fuel efficiency at elevated engine speeds in previous work. This study focuses on production viable solutions targeting similar volumetric efficiency benefits via delayed intake valve closure at these elevated engine speeds. Specifically, the production viable solutions include reducing the duration at peak lift, as well as reducing the amount of hardware required to achieve a delayed intake closure timing. It is demonstrated through simulation that delayed intake valve modulation at an elevated speed (2200 RPM) and load (12.7 bar BMEP) is capable of improving volumetric efficiency via a production viable lost motion enabled boot profile shape. Phased and dwell profiles were also evaluated. These profiles were compared against each other for two separately simulated cases: 1) modulating both intake valves per cylinder, and 2) modulating one of the two intake valves per cylinder. The boot, phase, and dwell profiles demonstrate volumetric efficiency improvements of up to 3.33%, 3.41%, and 3.5% respectively for two valve modulation, while realizing 2.79%, 2.59%, and 3.01% respectively for single valve modulation. As a result, this paper demonstrates that nearly all of the volumetric efficiency benefits achieved while modulating IVC via dwell profiles are possible with production viable boot and phased profiles
How to develop viruses into anticancer weapons (2017)

Viruses have shaped human history through devastating infections. In addition, virus infection may be responsible for up to 15% of cancer deaths [1]. Nevertheless, certain viruses can be our “friends.” At the end of the 18th century, Edward Jenner used cowpox to protect humans against infection with a lethal pathogen, smallpox. Based on the effectiveness of this “vaccination” process, in the 1960s, the World Health Organization mounted a global vaccination campaign that resulted in the eradication of smallpox [2].

In the mid-20th century, the principle of virus attenuation through adaptation to unnatural hosts was extended to cultured cells: cells from different species were used to select viruses with multiple mutations, reducing replication speed and allowing the immune system to control viral infection. Based on such a “live-attenuated” vaccine, global eradication of another viral disease, rinderpest, was recently achieved [3]. Other global vaccination campaigns, including those against polio and measles, are progressing. In addition, subunit vaccines are proving to be effective against virus-induced cancers, preventing hepatitis B virus–induced hepatocellular carcinoma and human papilloma virus–induced cervical cancer [2, 4].

A new frontier is to develop viruses into anticancer weapons. Many cancers remain incurable despite recent advances in radio-, chemo-, and immunotherapy. Based on their preferential replication in tumor cells, viruses from nine families have progressed to clinical trials of oncolysis: DNA viruses include Adenoviridae, Herpesviridae, Parvoviridae, and Poxviridae and RNA viruses Paramyxoviridae, Picornaviridae, Reoviridae, Retroviridae, and Rhabdoviridae [5, 6]. Recently, a genetically modified herpes simplex virus 1–based oncolytic vector, named talimogene laherparepvec (T-VEC), was approved as cancer therapeutic in the United States and Europe [7]. What are the mechanisms supporting cancer therapy with viruses, and how can oncolytic virotherapy be improved?
Picosecond On-Chip Qubit Control Circuitry (2005)

Fast on-chip control of superconducting qubits has engaged complex and power consuming RSFQ circuits that currently pose more of an experimental burden than an asset. Measurements of quantum coherent oscillations of qubits require dilution refrigerator temperatures. The motivation of this design is to minimize the necessary bias leads and power dissipation for an SFQ based control circuit. Elimination of redundant circuit elements by innovative use of fundamental elements allows small-scale control circuitry.
Identification and in Vivo Evaluation of Liver X Receptor β-Selective Agonists for the Potential Treatment of Alzheimer’s Disease (2016)

Herein, we describe the development of a functionally selective liver X receptor β (LXRβ) agonist series optimized for Emax selectivity, solubility, and physical properties to allow efficacy and safety studies in vivo. Compound 9 showed central pharmacodynamic effects in rodent models, evidenced by statistically significant increases in apolipoprotein E (apoE) and ATP-binding cassette transporter levels in the brain, along with a greatly improved peripheral lipid safety profile when compared to those of full dual agonists. These findings were replicated by subchronic dosing studies in non-human primates, where cerebrospinal fluid levels of apoE and amyloid-β peptides were increased concomitantly with an improved peripheral lipid profile relative to that of nonselective compounds. These results suggest that optimization of LXR agonists for Emax selectivity may have the potential to circumvent the adverse lipid-related effects of hepatic LXR activity.
Phase-Amplified Direct Detection of Atomic States for Heisenberg Limited Sensitivity in an Atomic Interferometer Employing Schroedinger Cat States (2017)

In a conventional atomic interferometer employing $N$ atoms, the phase sensitivity is at the standard quantum limit: $1/\sqrt{N}$. Using spin-squeezing, the sensitivity can be increased, either by lowering the quantum noise or via phase amplification, or a combination thereof. Here, we show how to increase the sensitivity, to the Heisenberg limit of $1/N$, while increasing the quantum noise by $\sqrt{N}$, thereby suppressing by the same factor the effect of excess noise. The protocol uses a Schrodinger Cat state representing a superposition of two collective states of $N$ atoms, behaving as a single entity with an $N$-fold increase in Compton frequency. The resulting $N$-fold phase magnification is revealed by using atomic state detection instead of collective state detection. We also show how to realize an atomic clock based on such a Schrodinger Cat state, with an $N$-fold increase in the effective transition frequency. We discuss potential experimental constraints for implementing this scheme, using one axis twist squeezing employing the cavity feedback scheme, and show that the effects of cavity decay and spontaneous emission are highly suppressed. We find that the maximum improvement in sensitivity can be close to the ideal limit, for as many as ten million atoms.
A reconfigurable QoS monitoring framework for professional short message services in GSM networks (2005)

In mobile environments, packet transmission services suffer from packet losses due to e.g. inadequate received signal quality, or forced by protocols in the signaling domain of the infrastructure of a mobile communications network. To reduce the occurrence of packet losses and, hence, to improve the quality of packet transmission services, such as e.g. the short message service (SMS) deployed in GSM (Global System for Mobile Communications) based mobile communications networks, a quantitative analysis of the quality of service (QoS) in the signaling domain is mandatory. For this reason, appropriate QoS parameters are needed. In this communication, the authors propose such QoS parameters and apply them to the SMS in GSM networks. Furthermore, a system framework for QoS monitoring, alerting and reconfiguring an SMS Center is presented. It operates near real-time and, therefore, helps to maintain a high QoS level. Selected monitoring results gathered during real world network operation are presented.
Ensembling Graph Predictions for AMR Parsing (2021)

In many machine learning tasks, models are trained to predict structure data such as graphs. For example, in natural language processing, it is very common to parse texts into dependency trees or abstract meaning representation (AMR) graphs. On the other hand, ensemble methods combine predictions from multiple models to create a new one that is more robust and accurate than individual predictions. In the literature, there are many ensembling techniques proposed for classification or regression problems, however, ensemble graph prediction has not been studied thoroughly. In this work, we formalize this problem as mining the largest graph that is the most supported by a collection of graph predictions. As the problem is NP-Hard, we propose an efficient heuristic algorithm to approximate the optimal solution. To validate our approach, we carried out experiments in AMR parsing problems. The experimental results demonstrate that the proposed approach can combine the strength of state-of-the-art AMR parsers to create new predictions that are more accurate than any individual models in five standard benchmark datasets.
Mildly Oxidized LDL Evokes a Sustained Ca 2+ -Dependent Retraction of Vascular Smooth Muscle Cells (1996)

Oxidized low density lipoprotein (LDL) is thought to play a major role in atherogenesis. Atherosclerotic arteries exhibit structural changes associated with profound alterations in vascular tone that are potentially involved in arterial spasm and ischemic heart disease. We report here the role of oxidized LDL in the retraction of vascular smooth muscle cells. Mildly oxidized LDL elicited a broad and sustained peak in cytosolic calcium concentration ([Ca2+]i) in cultured arterial smooth muscle cells. Concomitant with the [Ca2+]i rise, oxidized LDL evoked a sustained and intense retraction of smooth muscle cells, as shown by the changes in cross-sectional area of single cells. Cell retraction was dependent on time, the concentration of oxidized LDL, and the level of LDL oxidation (native LDL induced neither a significant [Ca2+]i rise nor cell retraction). Oxidized LDL but not native LDL also elicited a delayed (12 +/- 2 hours) and sustained (14 +/- 2 hours) increase in isometric tension in deendothelialized arterial rings only, thus suggesting a protective role of intact endothelium. When triggered by nontoxic doses of oxidized LDL, retraction of cultured cells and the contractile response of aortic rings was reversible, whereas with higher (toxic) doses (> or = 200 micrograms apoB/mL), cell retraction was irreversible and led progressively to detachment and cell death. Cell retraction can be prevented in three ways: (1) by inhibiting LDL oxidation with supplements of antioxidants (indirect inhibition); (2) by blocking the pathogenic intracellular signaling elicited by oxidized LDL (direct inhibition), eg, by inhibiting calcium influx with EGTA or the calcium channel blocker nisoldipine or by blocking intracellular signaling (at a still-unknown step) by the lipophilic antioxidant alpha-tocopherol; and (3) by directly inhibiting myosin light chain kinase by 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1, 4-diazepine. In conclusion, oxidized LDL evoked a sustained and intense calcium-dependent retraction of cultured smooth muscle cell, which can be prevented by inhibiting LDL oxidation or by blocking the intracellular signaling induced by oxidized LDL.
Benefit of Continuous Glucose Monitoring in Reducing Hypoglycemia Is Sustained Through 12 Months of Use Among Older Adults with Type 1 Diabetes (2022)

<b><i>Objective:</i></b> To evaluate glycemic outcomes in the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) randomized clinical trial (RCT) participants during an observational extension phase. <b><i>Research Design and Methods:</i></b> WISDM RCT was a 26-week RCT comparing continuous glucose monitoring (CGM) with blood glucose monitoring (BGM) in 203 adults aged ≥60 years with type 1 diabetes. Of the 198 participants who completed the RCT, 100 (98%) CGM group participants continued CGM (CGM-CGM cohort) and 94 (98%) BGM group participants initiated CGM (BGM-CGM cohort) for an additional 26 weeks. <b><i>Results:</i></b> CGM was used a median of >90% of the time at 52 weeks in both cohorts. In the CGM-CGM cohort, median time <70 mg/dL decreased from 5.0% at baseline to 2.6% at 26 weeks and remained stable with a median of 2.8% at 52 weeks (<i>P</i> < 0.001 baseline to 52 weeks). Participants spent more time in range 70-180 mg/dL (TIR) (mean 56% vs. 64%; <i>P</i> < 0.001) and had lower hemoglobin A1c (HbA1c) (mean 7.6% [59 mmol/mol] vs. 7.4% [57 mmol/mol]; <i>P</i> = 0.01) from baseline to 52 weeks. In BGM-CGM, from 26 to 52 weeks median time <70 mg/dL decreased from 3.9% to 1.9% (<i>P</i> < 0.001), TIR increased from 56% to 60% (<i>P</i> = 0.006) and HbA1c decreased from 7.5% (58 mmol/mol) to 7.3% (57 mmol/mol) (<i>P</i> = 0.025). In BGM-CGM, a severe hypoglycemic event was reported for nine participants while using BGM during the RCT and for two participants during the extension phase with CGM (<i>P</i> = 0.02). <b><i>Conclusions:</i></b> CGM use reduced hypoglycemia without increasing hyperglycemia in older adults with type 1 diabetes. These data provide further evidence for fully integrating CGM into clinical practice. Clinicaltrials.gov (NCT03240432).
Thunderstorm and fair-weather quasi-static electric fields over land and ocean (2021)

Natural lightning and the associated clouds are known to behave differently over land and ocean, but many questions remain. We expand the related observational datasets by obtaining simultaneous quasi-static electric field observations over coastal land, near-shore water, and deep ocean regions during both fair-weather and thunderstorm periods. Oceanic observations were obtained using two 3-m NOAA buoys that were instrumented with Campbell Scientific electric field mills to measure the quasi-static electric fields. These data were compared to selected electric field records from the existing on-shore electric field mill suite of 31 sensors at Kennedy Space Center (KSC). Lightning occurrence times, locations and peak current estimates for both onshore and ocean were provided by the U.S. National Lightning Detection Network. The buoy instruments were first evaluated on-shore at the Florida coast, and the first system was calibrated for field enhancements and to confirm proper behavior of the system in elevated-field environments. The buoys were then moored 20 mi and 120 mi off the coast of KSC in February (20 mi) and August (120 mi) 2014. Diurnal fair-weather fields at both ocean sites matched will with each other and with those found during the Carnegie cruise, but mean values were 33% smaller, due at least in-part to constraints on the calibration procedure. Diurnal fair-weather fields variations at coastal and inland sites were a poorer match than offshore, likely because the offshore environment is “cleaner” with limited variations in local space charge, lower surface aerosol densities, little surface heating to disturb the surface charge layer during fair weather, and fewer local radioactive sources to modulate the near-surface electrical conductivity. Storm-related static fields were 4-5× larger at both oceanic sites than over land, likely due to decreased screening by near-surface space charge produced by corona current. The time-evolution of the electric field and field changes during storm approach are sufficiently different over land and ocean to warrant further study. This work shows the quality, accuracy, and reliability of these data, and has demonstrated the practicality of off-shore electric field measurements for safety- and launch-related decision making at KSC.
Central and peripheral actions of a nonpeptidic angiotensin II receptor antagonist. (1990)

Nonpeptidic imidazole derivatives were recently reported to be angiotensin II receptor antagonists with acute blood pressure-lowering activity. In the present study, we characterized the angiotensin II receptor antagonist properties of one such derivative, 4'-([2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl)- [1,1'-biphenyl]-2-carboxylic acid (IMI). In receptor binding studies, IMI displaced bound [125I]angiotensin II from rat uterine membranes with an IC50 of 0.17 microM. In isolated rabbit aortic rings, IMI shifted the angiotensin II concentration-response curve to the right in a parallel and concentration-dependent manner. A Schild plot of these data indicated a pA2 of 7.13 +/- 0.16 and a slope of 0.94 +/- 0.06. In rat kidney slices, IMI shifted the concentration-response curve for angiotensin II-induced inhibition of renin release to the right. Antagonism of the angiotensin II pressor response by IMI was dose dependent and reversible in ganglion-blocked, anesthetized rats. The water intake and pressor responses to intracerebroventricular angiotensin II (100 pmol) were inhibited by intracerebroventricular IMI (25 or 50 nmol) in conscious Sprague-Dawley rats. Similarly, the drinking and pressor responses to intravenous angiotensin II were blocked by intravenous IMI in conscious rats. IMI alone had no effects on mean arterial pressure or drinking when administered either intravenously or intracerebroventricularly. IMI decreased mean arterial pressure throughout 5 days of infusion in spontaneously hypertensive rats. In summary, IMI was a full competitive antagonist without partial agonist activity in peripheral tissues and the central nervous system. Moreover, the chronic administration of this angiotensin II receptor antagonist was antihypertensive in spontaneously hypertensive rats.
Polarization interleaving to reduce inter-channel nonlinear penalties in polarization multiplexed transmission (2005)

We investigate through simulations and experiments inter-channel nonlinear penalties in 2/spl times/10 Gbit/s NRZ polarization-multiplexed transmission. We show that the inter-channel nonlinear penalties can be partially mitigated by polarization interleaved transmission of the polarization-multiplexed channels.
Interfacing Computer-Assisted Drafting and Design with the Building Loads Analysis and System Thermodynamics (BLAST) Program (1992)

Energy efficient building design requires in-depth thermal analysis. Existing Computer Aided Design and Drafting (CADD) software packages already enhance the productivity and quality of design. Thermal analysis tools use much the same information as that contained in CADD drawings to determine the most energy efficient design configuration during the design process. To use these analysis tools, data already contained in the CADD system must be re-keyed into the analysis packages. This project created an interface to automate the migration of data from CADD to the Building Loads Analysis System and Thermodynamics (BLAST) analysis program, which is an Army-standard system for evaluating building energy performance. Two interfaces were developed, one batch-oriented (IN2BLAS7) and one interactive (the Drawing Navigator). Lessons learned from the development of IN2BLAST were carried into the development of the Drawing Navigator, and the Drawing Navigator was field tested. Feedback indicated that useful automation of the data migration is possible, and that proper application of such automation can increase productivity.