gebhart/patrepeval huggingface dataset:
Reduction of Hepatic and Adipose Tissue Glucocorticoid Receptor Expression With Antisense Oligonucleotides Improves Hyperglycemia and Hyperlipidemia in Diabetic Rodents Without Causing Systemic Glucocorticoid Antagonism (2005)

Glucocorticoids (GCs) increase hepatic gluconeogenesis and play an important role in the regulation of hepatic glucose output. Whereas systemic GC inhibition can alleviate hyperglycemia in rodents and humans, it results in adrenal insufficiency and stimulation of the hypothalamic-pituitary-adrenal axis. In the present study, we used optimized antisense oligonucleotides (ASOs) to cause selective reduction of the glucocorticoid receptor (GCCR) in liver and white adipose tissue (WAT) and evaluated the resultant changes in glucose and lipid metabolism in several rodent models of diabetes. Treatment of ob/ob mice with GCCR ASOs for 4 weeks resulted in approximately 75 and approximately 40% reduction in GCCR mRNA expression in liver and WAT, respectively. This was accompanied by approximately 65% decrease in fed and approximately 30% decrease in fasted glucose levels, a 60% decrease in plasma insulin concentration, and approximately 20 and 35% decrease in plasma resistin and tumor necrosis factor-alpha levels, respectively. Furthermore, GCCR ASO reduced hepatic glucose production and inhibited hepatic gluconeogenesis in liver slices from basal and dexamethasone-treated animals. In db/db mice, a similar reduction in GCCR expression caused approximately 40% decrease in fed and fasted glucose levels and approximately 50% reduction in plasma triglycerides. In ZDF and high-fat diet-fed streptozotocin-treated (HFD-STZ) rats, GCCR ASO treatment caused approximately 60% reduction in GCCR expression in the liver and WAT, which was accompanied by a 40-70% decrease in fasted glucose levels and a robust reduction in plasma triglyceride, cholesterol, and free fatty acids. No change in circulating corticosterone levels was seen in any model after GCCR ASO treatment. To further demonstrate that GCCR ASO does not cause systemic GC antagonism, normal Sprague-Dawley rats were challenged with dexamethasone after treating with GCCR ASO. Dexamethasone increased the expression of GC-responsive genes such as PEPCK in the liver and decreased circulating lymphocytes. GCCR ASO treatment completely inhibited the increase in dexamethasone-induced PEPCK expression in the liver without causing any change in the dexamethasone-induced lymphopenia. These studies demonstrate that tissue-selective GCCR antagonism with ASOs may be a viable therapeutic strategy for the treatment of the metabolic syndrome.
New Medicinal Products for Chronic Heart Failure: Advances in Clinical Trial Design and Efficacy Assessment (2017)

Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
Unfolding four-helix bundles (2011)

A geometrical model has been developed to describe the early stages of unfolding of cytochromes c′ and c-b562 . Calculations are based on a step-wise extension of the polypeptide chain subject to the constraint that the spatial relationship among the residues of each triplet is fixed by the native-state crystallographic data. The response of each protein to these structural perturbations allows the evolution of each of the four helices in these two proteins to be differentiated. It is found that the two external helices in c′ unfold before its two internal helices, whereas exactly the opposite behaviour is demonstrated by c-b562 . Each of these cytochromes has an extended, internal, non-helical (‘turning’) region that initially lags behind the most labile helix but then, at a certain stage (identified for each cytochrome), unravels before any of the four helices present in the native structure. It is believed that these predictions will be useful in guiding future experimental studies on the unfolding of these two cytochromes.
Theory and Practice: Bulk Synthesis of C3B and its H2‐ and Li‐Storage Capacity (2015)

Previous theoretical studies of C3B have suggested that boron-doped graphite is a promising H2- and Li-storage material, with large maximum capacities. These characteristics could lead to exciting applications as a lightweight H2-storage material for automotive engines and as an anode in a new generation of batteries. However, for these applications to be realized a synthetic route to bulk C3B must be developed. Here we show the thermolysis of a single-source precursor (1,3-(BBr2)2C6H4) to produce graphitic C3B, thus allowing the characteristics of this elusive material to be tested for the first time. C3B was found to be compositionally uniform but turbostratically disordered. Contrary to theoretical expectations, the H2- and Li-storage capacities are lower than anticipated, results that can partially be explained by the disordered nature of the material. This work suggests that to model the properties of graphitic materials more realistically, the possibility of disorder must be considered.
A ±10ppm −40 to 125°C BAW-based frequency reference system for crystal-less wireless sensor nodes (2017)

A frequency reference system is implemented with a BAW-based 2.52GHz oscillator, divider, temperature sensor, digital PLL, and final test at three temperatures to create a 48MHz reference frequency with +/-10ppm stability from -40 to 125°C. This reference clock periodically recalibrates a fully integrated 32kHz RC oscillator to less than +/-500ppm frequency variation so that it can be used as the wireless node sleep timer. The reference system enables a Bluetooth Low Energy compliant radio in 65nm CMOS to be realized without any crystals.
Making C–C Bonds with Gold Catalysts: A Theoretical Study of the Influence of Gold Particle Size on the Dissociation of the C–X Bond in Aryl Halides (2014)

The adsorption and activation of iodo-, bromo-, and chlorobenzene over gold catalysts of different size, including an extended Au(111) surface; three-dimensional Au38 and Au13 nanoparticles; and planar Au7, Au6, and Au3 clusters has been systematically investigated by means of periodic density functional theory calculations. Several adsorption modes have been explored for each molecule, and the relative stability of such modes and the degree of C–X or C–C bond activation has been rationalized in terms of their molecular orbital distribution. Analysis of the electronic properties of the gold catalyst models allows the explanation of the influence of particle size on adsorption and activation energies in the subnanometer regime, while inclusion of dispersion interaction corrections becomes crucial for describing the reactivity of larger nanoparticles.
Guest Editorial: Special Issue on Selected Papers From IEEE ISCAS 2019 (2019)

The papers in this special section were presented at the 2019 IEEE International Symposium on Circuits and Systems (ISCAS 2019), that was held in Sapporo, Hokkaido, Japan from May 26 to 29, 2019.
Which search engine is best at finding airline site home pages (2001)

We evaluate the effectiveness of 20 Web search engines on 95 site finding queries. Each query names an airline, with the correct answer being the airline&amp;apos;s official home page URL (as listed by the International Air Transport Association). Performance varies widely across the 20 engines, indicating that site finding problem is not consistently well solved in practice. Users may wish to take this into account when deciding which engine to query.
Tra tipi e forme. Perche la sociologia urbana deve lavorare sulle dinamiche (2019)

This essay is based on revision and expansion of Weberian analysis of types of city in the era of world urbanization. The idea which the essay makes explicit is that planetary urbanization makes the different types of city closer, instead of doing these types unrelated. This takes place in distinct evolutionary paths. The essay has then elaborated on the connection between distinct spatial-territorial forms, a term which includes economy and society in their variable matching. The idea of assemblage is let aside, although relevant in recent urban theory. The Weberian category of urban political economy is then proposed, based on comparison of different types of city and the range of actors and economic-territorial systems taken into account.
Addressing Single Nitrogen-Vacancy Centers in Diamond with Transparent in-Plane Gate Structures (2014)

For many applications of the nitrogen-vacancy (NV) center in diamond, the understanding and active control of its charge state is highly desired. In this work, we demonstrate the reversible manipulation of the charge state of a single NV center from NV(-) across NV(0) to a nonfluorescent, dark state by using an all-diamond in-plane gate nanostructure. Applying a voltage to the in-plane gate structure can influence the energy band bending sufficiently for charge state conversion of NV centers. These diamond in-plane structures can function as transparent top gates, enabling the distant control of the charge state of NV centers tens of micrometers away from the nanostructure.
Development of ER Brake and its Application to Passive Force Display (2002)

Force display systems are important in virtual reality and other applications. While conventional force displays are active systems with actuators and as such may become inherently dangerous, passive force displays are effective methods for assuring safety. In this paper, we developed a brake using electrorheological (ER) fluid, and showed a passive force display system using ER brakes with two degrees of freedom. We also discuss basic control experiments of the system.
Inhibition of androgen/AR signaling inhibits diethylnitrosamine (DEN) induced tumour initiation and remodels liver immune cell networks (2021)

A promotional role for androgen receptor (AR) signaling in hepatocellular carcinogenesis is emerging. In pre-clinical models, including diethylnitrosamine- (DEN-) induced hepatocellular carcinoma (HCC), anti-androgen therapies delay hepatocarcinogenesis. However, pharmacologic anti-androgen therapy in advanced HCC patients fails, suggesting that AR plays a role in HCC onset. This study aims to characterize AR expression and function throughout DEN-induced liver inflammation and carcinogenesis and evaluate the efficacy of prophylactic AR antagonism to prevent hepatocarcinogenesis. We demonstrate that pharmacologic AR antagonism with enzalutamide inhibits hepatocellular carcinogenesis. With enzalutamide treatment, we observe decreased CYP2E1 expression, reducing DEN-induced hepatocyte death and DNA ethyl-adducts. AR protein expression analyses show that DEN causes an initial upregulation of AR in portal fibroblasts and leukocytes, but not hepatocytes, suggesting that hepatocyte-autonomous AR signaling is not essential for DEN-induced carcinogenesis. Ablating androgen signaling by surgical castration reduced pre-carcinogen Kupffer cell populations but did not alter DEN-mediated immune cell recruitment nor AR expression. In this study, we identified that anti-androgen interventions modulate mutagenic DNA adducts, tumour initiation, and immune cell composition. Additionally, we find that AR expression in hepatocytes is not present during nor required for early DEN-mediated carcinogenesis.
Fostering Innovation and Discovery in Biomedical Research (2005)

N TODAY’S SCIENTIFIC ERA,MOLECULAR RESEARCH HAS PAVED thewayforthedevelopmentofpharmaceuticalsthatare improving the lives of millions of patients. The discovery of the human immunodeficiency retrovirus as the causativeagentofAIDSledtothedevelopmentofreversetranscriptase inhibitors such as zidovudine. Monoclonal antibodiesdirectedagainsttumornecrosisfactorhavechanged the lives of many patients with rheumatoid arthritis. Imatinib mesylate, a specific inhibitor of the bcr-abl protein kinase,hastransformedtheprognosisforpatientswithchronic myeloid leukemia; and as drug-resistant variants arise, DNA sequencing can identify the mutations responsible and providearationalbasisforfurtherdrugdevelopment. 1,2 In2004 thefirstangiogenesisinhibitorswereapprovedbytheUSFood and Drug Administration, in one case for treatment of metastatic colorectal cancer and in another for age-related macular degeneration. 3,4 There is reason for optimism that this is justthebeginning,andthatthehugeinvestmentsinmolecular biology and genomics research made 10 to 30 years ago will provide an increasingly robust flow of new and effective medicines. Yet this gap of 10 to 30 years between discovery research andpharmaceuticalsbeingprescribedbyphysiciansalsogives
A combined joint diagonalization-MUSIC algorithm for subsurface targets localization (2014)

This paper presents a combined joint diagonalization (JD) and multiple signal classification (MUSIC) algorithm for estimating subsurface objects locations from electromagnetic induction (EMI) sensor data, without solving ill-posed inverse-scattering problems. JD is a numerical technique that finds the common eigenvectors that diagonalize a set of multistatic response (MSR) matrices measured by a time-domain EMI sensor. Eigenvalues from targets of interest (TOI) can be then distinguished automatically from noise-related eigenvalues. Filtering is also carried out in JD to improve the signal-to-noise ratio (SNR) of the data. The MUSIC algorithm utilizes the orthogonality between the signal and noise subspaces in the MSR matrix, which can be separated with information provided by JD. An array of theoreticallycalculated Green’s functions are then projected onto the noise subspace, and the location of the target is estimated by the minimum of the projection owing to the orthogonality. This combined method is applied to data from the Time-Domain Electromagnetic Multisensor Towed Array Detection System (TEMTADS). Examples of TEMTADS test stand data and field data collected at Spencer Range, Tennessee are analyzed and presented. Results indicate that due to its noniterative mechanism, the method can be executed fast enough to provide real-time estimation of objects’ locations in the field.
Self-organizing actin patterns shape membrane architecture but not cell mechanics (2017)

Cell-free studies have demonstrated how collective action of actin-associated proteins can organize actin filaments into dynamic patterns, such as vortices, asters and stars. Using complementary microscopic techniques, we here show evidence of such self-organization of the actin cortex in living HeLa cells. During cell adhesion, an active multistage process naturally leads to pattern transitions from actin vortices over stars into asters. This process is primarily driven by Arp2/3 complex nucleation, but not by myosin motors, which is in contrast to what has been theoretically predicted and observed in vitro. Concomitant measurements of mechanics and plasma membrane fluidity demonstrate that changes in actin patterning alter membrane architecture but occur functionally independent of macroscopic cortex elasticity. Consequently, tuning the activity of the Arp2/3 complex to alter filament assembly may thus be a mechanism allowing cells to adjust their membrane architecture without affecting their macroscopic mechanical properties.
A Cyclotrimerization Route to Cannabinoids (2008)

Three members of the cannabinoid class, cannabinol, cannabinol methyl ether, and cannabinodiol, were synthesized using a microwave-mediated [2 + 2 + 2] cyclotrimerization reaction as the key step. This approach provides a high level of synthetic flexibility allowing for the facile synthesis of cannabinoid analogues.
Acute Axonal Degeneration Drives Development of Cognitive, Motor, and Visual Deficits after Blast-Mediated Traumatic Brain Injury in Mice (2016)

Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain (<i>WldS</i>) of mice is resistant to some forms of axonal degeneration because of a triplicated fusion gene encoding the first 70 amino acids of Ufd2a, a ubiquitin-chain assembly factor, that is linked to the complete coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMAT1). Here, we demonstrate that resistance of <i>WldS</i> mice to axonal degeneration after blast-mediated TBI is associated with preserved function in hippocampal-dependent spatial memory, cerebellar-dependent motor balance, and retinal and optic nerve-dependent visual function. Thus, early axonal degeneration is likely a critical driver of subsequent neurobehavioral complications of blast-mediated TBI. Future therapeutic strategies targeted specifically at mitigating axonal degeneration may provide a uniquely beneficial approach to treating patients suffering from the effects of blast-mediated TBI.
Nonlinear Distortion of Acoustic Devices for Radio-Frequency Front-End Circuit and Its Suppression (2010)

In this paper, we discuss the nonlinear performance difference between surface acoustic wave (SAW) and bulk acoustic wave (BAW) resonators, which include intermodulation distortion (IMD) or triple-beat (TB) products, and indicate the importance of reducing even-order nonlinearities of BAW resonators. We were able to validate the accuracy and efficiency of our proposed simulation technique for BAW devices by comparing the results of our simulation with experimental data. We verified that our circuit model is a high-performance tool that can be used to predict BAW device nonlinearities, and we propose how to suppress even-order nonlinearities by employing a thin-film bulk acoustic resonator (FBAR) duplexer for wideband code division multiple access (WCDMA) band 1. Finally, we introduce highly linear FBAR duplexers.
Real-Time Measurement of Cellobiose and Glucose Formation during Enzymatic Biomass Hydrolysis (2021)

Enzymatic hydrolysis of lignocellulosic biomass for biofuel production relies on complex multi-enzyme ensembles. Continuous and accurate measurement of the released key products is crucial in optimizing the industrial degradation process and also investigating the activity and interaction between the involved enzymes and the insoluble substrate. Amperometric biosensors have been applied to perform continuous cellobiose measurements during the enzymatic hydrolysis of pure cellulose powders. The oxygen-sensitive mediators used in these biosensors restricted their function under physiological or industrial conditions. Also, the combined measurements of the hydrolysis products cellobiose and glucose require a high selectivity of the biorecognition elements. We employed an [Os(2,2'-bipyridine)<sub>2</sub>Cl]Cl-modified polymer and cellobiose dehydrogenase to fabricate a cellobiose biosensor, which can accurately and specifically detect cellobiose even in the presence of oxygen and the other main product glucose. Additionally, a glucose biosensor was fabricated to simultaneously measure glucose produced from cellobiose by β-glucosidases. The cellobiose and glucose biosensors work at applied potentials of +0.25 and +0.45 V versus Ag|AgCl (3 M KCl), respectively, and can selectively detect their substrate. Both biosensors were used in combination to monitor the hydrolysis of pure cellulose of low crystallinity or industrial corncob samples. The obtained results correlate with the high-performance liquid chromatography pulsed amperometric detection analysis and demonstrate that neither oxygen nor the presence of redox-active compounds from the lignin fraction of the corncob interferes with the measurements.
Data-driven Adaptive Benders Decomposition for the Stochastic Unit Commitment Problem (2019)

This paper proposes a data-driven version of the Benders decomposition algorithm applied to the stochastic unit commitment (SUC) problem. The proposed methodology aims at finding a trade-off between the size of the Benders master problem and the number of iterations until convergence. Using clustering techniques, we exploit the information contained in the Lagrange multipliers of the Benders subproblems in order to aggregate the optimality cuts, without compromising the critical information that is passed to the master problem. In addition, we develop an outer parallelization scheme that finds the optimal solution of the SUC problem by solving a series of less computationally intensive SUC instances for certain partitions of the scenario set. Our computational results on the IEEE 3-Area RTS-96 power system, illustrate the improved performance of our data-driven Benders algorithm, in terms of solution time and problem size, compared both to the SUC extensive formulation and to the prevailing single- and multi-cut Benders formulations.