gebhart/patrepeval huggingface dataset:
Alterations in circulating blood volume during polymicrobial sepsis. (1993)

Although a great deal is known concerning the pathophysiology of sepsis, it is not clear whether circulating blood volume (CBV) is altered under such conditions. To study, this, rats were subjected to sepsis by cecal ligation and puncture (CLP). Immediately after CLP or sham operation, the animals received 3 ml/100 g body weight normal saline subcutaneously. CBV was determined by using in vivo indocyanine green (ICG) clearance at 2, 5, 10, or 20 hr after CLP or sham operation. This technique does not require any blood sampling. Serum glutamic pyruvic transaminase (SGPT) and glutamic oxaloacetic transaminase (SGOT) were assayed enzymatically as indicators of hepatocyte damage. Hepatic microcirculation was assessed at a selected time point (10 hr post-CLP) by using laser Doppler flowmetry and colloidal carbon infusion techniques. The results indicate that CBV, as determined by ICG clearance, remained unchanged up to 10 hr following the onset of sepsis (i.e., early sepsis) but decreased significantly at 20 hr after CLP (late sepsis). However, systemic hematocrit increased significantly at 5, 10, and 20 hr after CLP, indicating that plasma volume decreased at those time points. This suggests that there may be limitations in accurately assessing CBV at 5 and 10 hr after CLP, i.e., during the hyperdynamic circulatory state of sepsis, using the ICG clearance method. Moreover, SGPT and SGOT levels increased significantly at 10 hr, and the levels increased further at 20 hr post-CLP. In contrast, microvascular blood flow and carbon-perfused areas in the liver were significantly increased at 10 hr post-CLP.
Antihormones in Prevention and Treatment of Breast Cancer (2006)

Breast cancer has the highest incidence of all types of cancer in women. Age and family history are the strongest risk factors, but sex hormones also play an important role, as demonstrated by epidemiological studies reporting a consistent association by reproductive personal history and breast cancer risk. The acceptability of preventive strategies by healthy women is closely related to their lifetime risk of developing breast cancer. Although surgical prevention may be considered in carriers of BRCA1/2 mutation, this option cannot be advocated for the majority of women whose risk is only moderately increased. In these women, chemoprevention with tamoxifen may reduce the incidence of estrogen receptor (ER)-positive breast carcinoma by 30-50%. Other drugs such as raloxifen and aromatase inhibitors (AIs) are currently being tested in this setting. Tamoxifen has been the most successful hormonal treatment over the last 30 years and, until recently, the most active drug in endocrine-sensitive breast cancer. In premenopausal breast cancer, tamoxifen still represents the therapy of choice, alone or in association with ovarian suppression. Conversely, in postmenopausal women it has been overtaken by third-generation AIs as first-choice drugs both in the adjuvant and metastatic settings. Many other issues, such as the optimal sequence between tamoxifen and AIs, the duration of AIs treatment, and the association of ovarian suppression and AIs in premenopausal patients still await the completion of randomized clinical trials. Furthermore, it is likely that treatment tailoring will be increased by the definition of patient subgroups that could derive larger benefits from AIs (progesterone receptor-negative, HER-2-overexpressing) or other new drugs.
A fast conformational search strategy for finding low energy structures of model proteins (1996)

We describe a new computer algorithm for finding low-energy conformations of proteins. It is a chain-growth method that uses a heuristic bias function to help assemble a hydrophobic core. We call it the Core-directed chain Growth method (CG). We test the CG method on several well-known literature examples of HP lattice model proteins [in which proteins are modeled as sequences of hydrophobic (H) and polar (P) monomers], ranging from 20-64 monomers in two dimensions, and up to 88-mers in three dimensions. Previous nonexhaustive methods--Monte Carlo, a Genetic Algorithm, Hydrophobic Zippers, and Contact Interactions--have been tried on these same model sequences. CG is substantially better at finding the global optima, and avoiding local optima, and it does so in comparable or shorter times. CG finds the global minimum energy of the longest HP lattice model chain for which the global optimum is known, a 3D 88-mer that has only been reachable before by the CHCC complete search method. CG has the potential advantage that it should have nonexponential scaling with chain length. We believe this is a promising method for conformational searching in protein folding algorithms.
Enzymatic Dehydrogenative Polymerization of Urushiols in Fresh Exudates from the Lacquer Tree, <i>Rhus vernicifera</i> DC (2007)

Fresh exudates from the lacquer tree, Rhus vernicifera DC, were extracted with acetone and the solution was chromatographed to isolate monomer, dimer, trimer, and oligomer fractions of urushiols. Constituents of the monomeric and dimeric fractions were then identified by two-dimensional (2D) 1H-13C heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond coherence (HMBC) NMR spectroscopic techniques. The results showed that the monomeric fraction contained 3-[8'Z,11'E,13'Z-pentadecatrienyl]catechol (1), 3-[8'Z,11'Z,14'-pentadecatrienyl]catechol (2), and 3-pentadecanyl]catechol (3), which was verified by HPLC analysis. The dimeric fraction contained 8'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[9'E,11'E,13'Z-pentadecatrienyl]catechol (4), 14'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecatrienyl]catechol (5), 2-hydroxyl-3- or -6-alkenylphenyl ethyl ether (6), 14'-(3' ',4' '-dihydroxy-2' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadeca-trienyl]catechol (7), 15'-(2' '-hydroxy-3' '- or -6' '-alkenyl)phenyloxy-3-[8'Z,11'Z,13'E)-pentadecatrienyl]catechol (8), 14'-(2' ',3' '-dihydroxy-4' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecantrienyl]catechol (9), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,3'-biphenyl (10), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,4'-biphenyl (11), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-5,4'-biphenyl (12), and 1,2,1'-trihydroxy-6,6'-dialkenyldibenzofuran (13) as constituents. In addition, dimeric ethers and peroxides, such as compounds 14 and 15, were produced by autoxidation of monomeric urushiols in atmospheric air. The possible reaction mechanisms for the dehydrogenative polymerization of urushiols by Rhus laccase present in the fresh raw exudates under the atmospheric oxygen are discussed on the basis of structures identified. This is of primary importance because the use of the urushi exudates as coating materials does not involve organic solvents and is an environmentally friendly process.
Sex‐Specific Impact of Aldosterone Receptor Antagonism on Ventricular Remodeling and Gene Expression after Myocardial Infarction (2009)

Aldosterone receptor antagonism reduces mortality and improves post-myocardial infarction (MI) remodeling. Because aldosterone and estrogen signaling pathways interact, we hypothesized that aldosterone blockade is sex-specific. Therefore, we investigated the impact of eplerenone on left ventricular (LV) remodeling and gene expression of male infarcted rats versus female infarcted rats. MI and Sham animals were randomized to receive eplerenone (100 mg/kg/day) or placebo 3 days post-surgery for 4 weeks and assessed by echocardiography. In the MI placebo group, left ventricular end-diastolic dimension (LVEDD) increased from 7.3 +/- 0.4 mm to 10.2 +/- 1.0 mm (p < 0.05) and ejection fraction (EF) decreased from 82.3 +/- 4% to 45.5 +/- 11% (p < 0.05) in both sexes (p = NS between groups). Eplerenone attenuated LVEDD enlargement more effectively in females (8.8 +/- 0.2 mm, p < 0.05 vs. placebo) than in males (9.7 +/- 0.2 mm, p = NS vs. placebo) and improved EF in females (56.7 +/- 3%, p < 0.05 vs. placebo) but not in males (50.6 +/- 3%, p = NS vs. placebo). Transcriptomic analysis using Rat_230-2.0 microarrays (Affymetrix) revealed that in females 19% of downregulated genes and 44% of upregulated genes post-MI were restored to normal by eplerenone. In contrast, eplerenone only restored 4% of overexpressed genes in males. Together, these data suggest that aldosterone blockade reduces MI-induced cardiac remodeling and phenotypic alterations of gene expression preferentially in females than in males. The use of transcriptomic signatures to detect greater benefit of eplerenone in females has potential implications for personalized medicine.
Quantitative characterization of the eddy current fields in a 40‐cm bore superconducting magnet (1994)

The temporal and spatial dependence of the eddy current fields, generated by switching off x, y, and z gradients in a 40-cm bore Bruker superconducting magnet, have been studied by measuring the offset frequency of the proton FID obtained from a small spherical sample. The measurements were made with the pre-emphasis unit deactivated. The data obtained at each location were well fitted to a sum of four exponentially decaying components. The shortest decay is, in each case, associated with the decay of the current in the gradient coil itself, while the other decays are associated with three eddy currents with decay times ranging from 13 to 480 ms. Each of the three eddy currents generates an essentially uniform gradient for at least 4 cm on either side of the isocenter. However, when the eddy currents are generated by either the vertical transverse gradient or the longitudinal gradient, the eddy current gradients are also accompanied by a field shift.
Irradiation of necrotic cancer cells, employed for pulsing dendritic cells (DCs), potentiates DC vaccine-induced antitumor immunity against high-grade glioma (2015)

Dendritic cell (DC)-based immunotherapy has yielded promising results against high-grade glioma (HGG). However, the efficacy of DC vaccines is abated by HGG-induced immunosuppression and lack of attention toward the immunogenicity of the tumor lysate/cells used for pulsing DCs. A literature analysis of DC vaccination clinical trials in HGG patients delineated the following two most predominantly applied methods for tumor lysate preparation: freeze-thaw (FT)-induced necrosis or FT-necrosis followed by X-ray irradiation. However, from the available clinical evidence, it is unclear which of both methodologies has superior immunogenic potential. Using an orthotopic HGG murine model (GL261-C57BL/6), we observed that prophylactic vaccination with DCs pulsed with irradiated FT-necrotic cells (compared to FT-necrotic cells only) prolonged overall survival by increasing tumor rejection in glioma-challenged mice. This was associated, both in prophylactic and curative vaccination setups, with an increase in brain-infiltrating Th1 cells and cytotoxic T lymphocytes (CTL), paralleled by a reduced accumulation of regulatory T cells, tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC). Further analysis showed that irradiation treatment of FT-necrotic cells considerably increased the levels of carbonylated proteins - a surrogate-marker of oxidation-associated molecular patterns (OAMPs). Through further application of antioxidants and hydrogen peroxide, we found a striking correlation between the amount of lysate-associated protein carbonylation/OAMPs and DC vaccine-mediated tumor rejection capacity thereby suggesting for the first time a role for protein carbonylation/OAMPs in at least partially mediating antitumor immunity. Together, these data strongly advocate the use of protein oxidation-inducing modalities like irradiation for increasing the immunogenicity of tumor lysate/cells used for pulsing DC vaccines.
Increasing the Awareness of Daily Activity Levels with Pervasive Computing (2006)

Public health promotion technology should be accessible to the general public at which it is aimed. This paper explores the potential for use of an unaugmented commodity technology - the mobile phone - as a health promotion tool. We describe a prototype application that tracks the daily exercise activities of people carrying phones, using fluctuation in signal strength to estimate a user's movement. In a short-term study of the prototype that shared activity information amongst groups of friends, we found that awareness encouraged reflection on, and increased motivation for, daily activity. We describe some of the details of the pilot study, and conclude with our intended plans to develop the system further in order to carry out a longer-term clinical trial
Encapsulation of small magnetic clusters in fullerene cages: A density functional theory investigation within van der Waals corrections (2012)

The encapsulation of magnetic transition-metal (TM) clusters inside carbon cages (fullerenes, nanotubes) has been of great interest due to the wide range of applications, which spread from medical sensors in magnetic resonance imaging to photonic crystals. Several theoretical studies have been reported; however, our atomistic understanding of the physical properties of encapsulated magnetic TM $3d$ clusters is far from satisfactory. In this work, we will report general trends, derived from density functional theory within the generalized gradient approximation proposed by Perdew, Burke, and Ernzerhof (PBE), for the encapsulation properties of the TM${}_{m}$@C${}_{n}$ (TM $=$ Fe, Co, Ni; $m=2\ensuremath{-}6$, $n=60,70,80,90$) systems. Furthermore, to understand the role of the van der Waals corrections to the physical properties, we employed the empirical Grimme's correction ($\mathrm{PBE}+\mathrm{D}2$). We found that both PBE and $\mathrm{PBE}+\mathrm{D}2$ functionals yield almost the same geometric parameters, magnetic and electronic properties, however, $\mathrm{PBE}+\mathrm{D}2$ strongly enhances the encapsulation energy. We found that the center of mass of the TM${}_{m}$ clusters is displaced towards the inside C${}_{n}$ surfaces, except for large TM${}_{m}$ clusters ($m=5$ and 6). For few cases, e.g., Co${}_{4}$ and Fe${}_{4}$, the encapsulation changes the putative lowest-energy structure compared to the isolated TM${}_{m}$ clusters. We identified few physical parameters that play an important role in the sign and magnitude of the encapsulation energy, namely, cluster size, fullerene equatorial diameter, shape, curvature of the inside C${}_{n}$ surface, number of TM atoms that bind directly to the inside C${}_{n}$ surface, and the van der Waals correction. The total magnetic moment of encapsulated TM${}_{m}$ clusters decreases compared with the isolated TM${}_{m}$ clusters, which is expected due to the hybridization of the $d\ensuremath{-}p$ states, and strongly depends on the size and shape of the fullerene cages.
Menin and PRMT5 suppress GLP1 receptor transcript and PKA-mediated phosphorylation of FOXO1 and CREB (2017)

Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic β-cell proliferation. Tamoxifen-inducible deletion of multiple endocrine neoplasia type 1 (<i>MEN1</i>) gene, which encodes the protein menin, increases β-cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of β-cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling. Here, we show that menin and protein arginine methyltransferase 5 (PRMT5) suppress GLP1 receptor (GLP1R) transcript levels. Notably, a GLP1R agonist induces phosphorylation of forkhead box protein O1 (FOXO1) at S253, and the phosphorylation is mediated by PKA. Interestingly, menin suppresses GLP1-induced and PKA-mediated phosphorylation of both FOXO1 and cAMP response element binding protein (CREB), likely through a protein arginine methyltransferase. Menin-mediated suppression of FOXO1 and CREB phosphorylation increases FOXO1 levels and suppresses CREB target genes, respectively. A small-molecule menin inhibitor reverses menin-mediated suppression of both FOXO1 and CREB phosphorylation. In addition, ex vivo treatment of both mouse and human pancreatic islets with a menin inhibitor increases levels of proliferation marker Ki67. In conclusion, our results suggest that menin and PRMT5 suppress GLP1R transcript levels and PKA-mediated phosphorylation of FOXO1 and CREB, and a menin inhibitor may reverse this suppression to induce β-cell proliferation.
Preliminary experimental evaluation of an inverse source imaging procedure using a decoupled coil detector array in magnetic resonance imaging (1995)

Recently, we have discussed several of the aspects involved in the detector array concept in magnetic resonance imaging where an image is obtained by applying inverse source procedures to the data assembled by an array of coil detectors surrounding the object. In this work we describe an experimental setup, where a detector array was constructed of 9 coils, that gives a coarse resolution of 3 x 3 pixels. By measuring the induced current signals over this array of coils, a relationship is established between the set of signals and the structure of the body under investigation. Through matrix inversion, reconstruction of the original source from the detected signals is possible. In this preliminary experimental setup, we did not use an actual nuclear magnetic resonance signal. Instead, a miniature solenoid was used as a source, to simulate a precessing magnetic moment.
Noise-Controlled Signal Transmission in a Multithread Semiconductor Neuron (2009)

We report on stochastic effects in a new class of semiconductor structures that accurately imitate the electrical activity of biological neurons. In these devices, electrons and holes play the role of K+ and Na+ ions that give the action potentials in real neurons. The structure propagates and delays electrical pulses via a web of spatially distributed transmission lines. We study the transmission of a periodic signal through a noisy semiconductor neuron. Using experimental data and a theoretical model we demonstrate that depending on the noise level and the amplitude of the useful signal, transmission is enhanced by a variety of nonlinear phenomena, such as stochastic resonance, coherence resonance, and stochastic synchronization.
Advances in the chemical conversion of energetic materials to higher value products (1995)

The objective of this program is to develop novel, innovative solutions for the disposal of surplus explosives resulting from the demilitarization of nuclear and conventional munitions by DOE and DoD. Studies related to the conversion of TNT and Explosive D to potentially useful materials are described. The paper describes the feasibility of conversion of TNT to TATB; conversion of TNT to 3,5-diamino-2,4,6-trinitrotoluene (DATNT); conversion of TNT to tolylene 2,4-diisocyanate (TDI) and nitrotolylene and diisocyanate (NTDI); chelating resins derived from trinitroarenes.
Instruction execution trade-offs for SIMD vs. MIMD vs. mixed mode parallelism (2002)

Mixed-mode parallel processors can quickly switch from executing instructions in single instruction, multiple data stream (SIMD) mode to executing them in multiple instruction, multiple data stream (MIMD) mode. To fully exploit this capability, the circumstances under which each mode should be used must be understood. This paper explores mixed-mode parallelism by presenting a general overview of the trade-offs between SIMD and MIMD modes, and then characterizing in detail three of the trade-offs concerning instruction execution performance. These include the effect of overlapping control unit and processor execution in SIMD mode, performance of conditional statements, and the consequences of switching parallelism modes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes (2008)

Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts anti-inflammatory effects in two animal models of type I diabetes. Type I diabetes was induced chemically with streptozotocin or genetically using the non-obese diabetic (NOD) female mouse model. Mice were treated with INO-2002 or inosine as required at 30, 100, or 200 mg/kg per day, while blood glucose and diabetes incidence were monitored. The effect of INO-2002 on the pancreatic cytokine profile was also determined. INO-2002 reduced both the hyperglycaemia and incidence of diabetes in both streptozotocin-induced and spontaneous diabetes in NOD mice. INO-2002 proved to be more effective in protecting against diabetes than the naturally occurring purine, inosine, when administered at the same dose. INO-2002 treatment decreased pancreatic levels of interleukin (IL)-12 and tumour necrosis factor-alpha, while increasing levels of IL-4 and IL-10. INO-2002 also reduced pancreatic levels of the chemokine MIP-1 alpha. The inosine analogue, INO-2002, was protected more effectively than the naturally occurring purine, inosine, against development of diabetes in two separate animal models. INO-2002 exerts protective effects by changing the pancreatic cytokine expression from a destructive Th1 to a protective Th2 profile. The use of analogues of inosine such as INO-2002 should be considered as a potential preventative therapy in individuals susceptible to developing type I diabetes.
The <i>Rx</i> Gene from Potato Controls Separate Virus Resistance and Cell Death Responses (1999)

Rx-mediated extreme resistance against potato virus X in potato does not involve a necrotic hypersensitive response at the site of initial infection and thereby differs from the more usual type of disease resistance in plants. However, the Rx protein is structurally similar to products of disease resistance genes conferring the hypersensitive response. We show in both Nicotiana spp and potato that Rx has the potential to initiate a cell death response but that extreme resistance is separate and epistatic to necrosis. These data indicate that cell death and pathogen arrest are separate disease resistance responses in plants.
Design Rules for Charge-Transport Efficient Host Materials for Phosphorescent Organic Light-Emitting Diodes (2012)

The use of blue phosphorescent emitters in organic light-emitting diodes (OLEDs) imposes demanding requirements on a host material. Among these are large triplet energies, the alignment of levels with respect to the emitter, the ability to form and sustain amorphous order, material processability, and an adequate charge carrier mobility. A possible design strategy is to choose a π-conjugated core with a high triplet level and to fulfill the other requirements by using suitable substituents. Bulky substituents, however, induce large spatial separations between conjugated cores, can substantially reduce intermolecular electronic couplings, and decrease the charge mobility of the host. In this work we analyze charge transport in amorphous 2,8-bis(triphenylsilyl)dibenzofuran, an electron-transporting material synthesized to serve as a host in deep-blue OLEDs. We show that mesomeric effects delocalize the frontier orbitals over the substituents recovering strong electronic couplings and lowering reorganization energies, especially for electrons, while keeping energetic disorder small. Admittance spectroscopy measurements reveal that the material has indeed a high electron mobility and a small Poole-Frenkel slope, supporting our conclusions. By linking electronic structure, molecular packing, and mobility, we provide a pathway to the rational design of hosts with high charge mobilities.