gebhart/patrepeval huggingface dataset:
Increased extracellular water compartment, relative to intracellular water compartment, after weight reduction (1999)

The hydration of fat free mass (FFM) and extracellular (ECW) and intracellular water (ICW) compartments were studied in 30 obese premenopausal women before and after a 3-mo weight-reduction program and again after a 9-mo weight-maintenance program. Body fat was determined by a four-compartment model. Total body water and ECW were determined by deuterium dilution and bromide dilution, respectively. After the weight-reduction period, mean weight loss was 12.8 kg, and body fat was reduced on average by 10.9 kg. During weight maintenance, changes in body mass and body fat were not significant. Before weight reduction, mean ECW/ICW ratio was relatively high (0.78 +/- 0.10). During the the study, total body water and ICW did not change significantly. ECW did not change significantly after weight reduction, but 12 mo after the start ECW was significantly increased by 1 liter. The ECW/ICW ratio increased to 0.87 +/- 0.12 (month 12). The hydration of the FFM increased from 74 +/- 1 to 77 +/- 2% during the weight reduction and remained elevated during weight maintenance. In conclusion, the ECW/ICW ratio and the hydration of the FFM, did not normalize during weight reduction and weight maintenance.
Ca 2+ /Calmodulin-Dependent Protein Kinase II Phosphorylation of Ryanodine Receptor Does Affect Calcium Sparks in Mouse Ventricular Myocytes (2006)

Previous studies in transgenic mice and with isolated ryanodine receptors (RyR) have indicated that Ca2+-calmodulin-dependent protein kinase II (CaMKII) can phosphorylate RyR and activate local diastolic sarcoplasmic reticulum (SR) Ca2+ release events (Ca2+ sparks) and RyR channel opening. Here we use relatively controlled physiological conditions in saponin-permeabilized wild type (WT) and phospholamban knockout (PLB-KO) mouse ventricular myocytes to test whether exogenous preactivated CaMKII or endogenous CaMKII can enhance resting Ca2+ sparks. PLB-KO mice were used to preclude ancillary effects of CaMKII mediated by phospholamban phosphorylation. In both WT and PLB-KO myocytes, Ca2+ spark frequency was increased by both preactivated exogenous CaMKII and endogenous CaMKII. This effect was abolished by CaMKII inhibitor peptides. In contrast, protein kinase A catalytic subunit also enhanced Ca2+ spark frequency in WT, but had no effect in PLB-KO. Both endogenous and exogenous CaMKII increased SR Ca2+ content in WT (presumably via PLB phosphorylation), but not in PLB-KO. Exogenous calmodulin decreased Ca2+ spark frequency in both WT and PLB-KO (K0.5 approximately 100 nmol/L). Endogenous CaMKII (at 500 nmol/L [Ca2+]) phosphorylated RyR as completely in <4 minutes as the maximum achieved by preactivated exogenous CaMKII. After CaMKII activation Ca2+ sparks were longer in duration, and more frequent propagating SR Ca2+ release events were observed. We conclude that CaMKII-dependent phosphorylation of RyR by endogenous associated CaMKII (but not PKA-dependent phosphorylation) increases resting SR Ca2+ release or leak. Moreover, this may explain the enhanced SR diastolic Ca2+ leak and certain triggered arrhythmias seen in heart failure.
Noninvasive Electrocardiographic Imaging (1997)

The study demonstrates that ECGI can reconstruct epicardial potentials, electrograms, and isochrones over the entire epicardial surface during the cardiac cycle. It can provide detailed information on local activation of the heart noninvasively. Its uses could include localization of cardiac electric events (eg, ectopic foci), characterization of nonuniformities of conduction, characterization of repolarization properties (eg, dispersion), and mapping of dynamically changing arrhythmias (eg, polymorphic VT) on a beat-by-beat basis.
Opening Of A Pressurized Fracture In An Elastic Medium (1971)

Abstract In this paper a numerical procedure is presented for the calculation of the openingof an internally pressurized equilibrium line crack in an infinite elastic solid. The method is based on England and Green'sintegral equations and allows a solution to be obtained for any pressure distribution along the crack length. As an example, theproblem of Christianovich and Zheltov (constant pressure along a portion of the crack length) is solved numerically and shown to be in excellent agreement with analytical results. Also, the numerical solutions toa number of other pressure functions are presented here. The paper is prepared with the idea of using its findings in the design of a hydraulic fracture. Introduction In order to design a hydraulic fracture one needs to know the quantitative expression yielding the opening of an internally pressurized crack in an infinite medium. The derivation of such an expression is hindered by the mathematical problemsencountered during a formal solution. Thus one makes the assumption that the medium is isotropic, homogeneous and linearly elastic) that the crack is two dimensional, i.e., no variations in its geometry in the third dimension, and that the plane of the crack is under the influence of a constant hydrostatic stress (-S) at infinity (compression negative). Under these assumptions the fracture propagates along a straight line (line crack) and the problem is reduced to the calculation of the opening of an internally pressurized two-dimensional line crack in an infinite elastic solid. In order to cause any fracture opening, the magnitude of the-internal pressure in the crack must be sufficientlylarge to:apply enough force on the crack walls to neutralize the opposite force due to the far-field stress (-S) andprovide the required energy to account for the change in the strain energy of the deformed body. Crack extension starts when the tensile stresses induced at thecrack tip equal or exceed a critical value and cease when the potential energy or the system attains a minimum (the condition for stable equilibrium). The solution of the "moving" crack problem is difficult to obtain and is beyond the scope of the present work. Thus it is assumed that the internal pressure is not large enough to cause a fracture extension. This means that even if this pressure has been sufficient at some point in the past to cause an extension, enough time has passed for the crack to reach a state of stable equilibrium. The problem of a two-dimensional line crack in an infinite elastic solid under the influence of a constant internal pressure has been solved by Sneddon.1 He found that under these conditions the crack deforms into an ellipse and derived the mathematical expressions for the opening of the fracture. For the case of variable pressure along the crack length, Sneddon and Elliot 2 have derived equations yielding the crack opening. The use of these equations requires the Maclaurin series expansion of the function describing the pressure variations along the crack length.
Fc glycans of therapeutic antibodies as critical quality attributes (2015)

Critical quality attributes (CQA) are physical, chemical, biological or microbiological properties or characteristics that must be within an appropriate limit, range or distribution to ensure the desired product quality, safety and efficacy. For monoclonal antibody therapeutics that rely on fraction crystalizable (Fc)-mediated effector function for their clinical activity, the terminal sugars of Fc glycans have been shown to be critical for safety or efficacy. Different glycosylation variants have also been shown to influence the pharmacodynamic and pharmacokinetic behavior while other Fc glycan structural elements may be involved in adverse immune reactions. This review focuses on the role of Fc glycans as CQAs. Fc glycan information from the published literature is summarized and evaluated for impact on patient safety, immunogenicity, bioactivity and pharmacodynamics/pharmacokinetics.
Expression of IgG Fc receptor antigens in placenta and on endothelial cells in humans. An immunohistochemical study. (1991)

Expression of leukocyte IgG Fc receptor (Fc gamma R) antigens by placenta, endothelial cells (EC) of normal tissues, and ECs of kidney and skin from subjects with immune complex diseases was studied immunohistochemically using anti-Fc gamma R monoclonal antibodies (MAb). Monoclonal antibodies against all three leukocyte Fc gamma R classes stained placental villous macrophages. Placental villous trophoblasts were stained intensely by anti-Fc gamma RIII MAb 3G8, while both anti-Fc gamma RI (MAb 32) and anti-Fc gamma RII MAbs IV3, KU79, CIKM5, 2E1, KB61, and 41H16) antibodies did not react with these cells. Anti-Fc gamma RII MAbs IV3, KU79, CIKM5, 2E1, KB61, and 41H16 immunostained placental villous capillary EC, in contrast to anti-Fc gamma RI MAb 32 and anti-Fc gamma RIII MAb 3G8, CLB-Granl, and B73.1, which did not bind. Anti-Fc gamma RI MAb 32, anti-Fc gamma RII MAb IV3 and CIKM5, and anti-Fc gamma RIII MAb 3G8 did not react with the ECs of tonsil, liver, kidney, spleen, intestine, lung, or uterus. Similarly no EC staining was seen with these four MAbs in 14 skin and 14 kidney biopsies from subjects with immune-complex diseases. Fc gamma R antigens are expressed constitutively only by placental villous ECs and are not induced on nonplacental ECs by immune-complex-mediated diseases.
Efficient mapping of protein antigenic determinants. (1986)

A recombinant DNA expression strategy has been used to deduce the amino acid sequences of six different antigenic determinants in a single protein of Mycobacterium leprae, the etiologic agent of leprosy. The gene encoding the M. leprae 65-kDa antigen was sequenced and a lambda gt11 gene sublibrary was constructed with fragments of the gene. Recombinant DNA clones producing specific antigenic determinants were isolated by screening with monoclonal antibodies, and the sequences of their insert DNAs were determined with a rapid primer-extension method. The amino acid sequence of each determinant was deduced from the minimum overlap of insert DNAs from multiple antibody-positive DNA clones. Amino acid sequences for six different epitopes were elucidated. A peptide containing sequences for one of these epitopes was synthesized and shown to bind the appropriate monoclonal antibody; this antigenic determinant is unique to M. leprae. The approach described here can be used to rapidly elucidate protein epitopes that are recognized by antibodies or T cells.
Modified Cyclodextrins: Scaffolds and Templates for Supramolecular Chemistry (1999)

Cyclodextrin structure and complexation behaviour strategies for synthesis intramolecular complexation, chiral discrimination and photochemical devices cyclodextrin catalysts and enzyme mimics metallocyclodextrins multisite complexation of guests and linked cyclodextrins cyclodextrin rotaxanes and catenanes surface and interface behaviour.
Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques (2017)

Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.
Targeted Disruption of the Chemokine Eotaxin Partially Reduces Antigen-induced Tissue Eosinophilia (1997)

The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C-C chemokine implicated in the recruitment of eosinophils in a variety of inflammatory disorders and, unlike all other eosinophil chemoattractants, is eosinophil specific. However, given the large number of chemoattractants that have activities on eosinophils, it is unclear whether eotaxin has an important role in vivo. Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation. To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin. Such mice demonstrate that eotaxin enhances the magnitude of the early (but not late) eosinophil recruitment after antigen challenge in models of asthma and stromal keratitis. Surprisingly, a role for eotaxin in regulating the constitutive number of eosinophils in the peripheral circulation is also demonstrated. These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.
WINTER ROAD MAINTENANCE SYSTEM (1995)

VVHS is a data-base tool for improving winter maintenance and making it more effective. VVHS supports all sorts of work, including preseason planning, implementation of follow-up measures, and evaluation of completed work. During the planning phase, VVHS allows users to optimize resource utilization and timing of maintenance. Optimized plans for different situations such as skid control and snowplowing can be used to yield expected results at the lowest possible cost. The consideration of time improves the quality of plans. During work, any deviation from planned ending times for activities can be pinpointed and compensated for by VVHS. VVHS can help gather information on ongoing operations, making information on completion times, resource utilization, and material use easily available for future decision making. In turn, agencies can make information about their winter maintenance operations and traffic conditions available to the public.
Diaphragm Pacing during Mechanical Ventilation: Development of a Control Algorithm and Analysis of Respiratory Mechanics (2013)

Prolonged totally controlled mechanical ventilation results in the complete absence of mechanical activity of the diaphragm leading to rapid loses in diaphragmatic function, a syndrome known as Ventilator-Induced Diaphragmatic Dysfunction VIDD. Electrical activation of the diaphragm by phrenic nerve stimulation may prevent diaphragm atrophy in sedated patients undergoing Controlled Mechanical Ventilation CMV. The aims of this thesis were to develop a control algorithm to pace the diaphragm in-synchrony with a ventilator during controlled mechanical ventilation in critically-ill patients and analyze the respiratory mechanics resulting from such co-ordinated inspiratory action of the diaphragm and the mechanical ventilator. The algorithm was verified through bench tests and evaluated in an animal model. In the animal study, the respiratory mechanics were also analyzed to better understand the effects of synchronous diaphragm pacing during mechanical ventilation and to identify an optimal level of pacing support during mechanical ventilation for clinical applications.
Toward surgical angiogenesis using slow-released basic fibroblast growth factor (2003)

Biodegradable hydrogel microspheres with bFGF improved LV function and inhibited LV remodeling by angiogenesis in pigs with chronic myocardial infarction. bFGF microspheres into ischemic myocardium may revascularize small ungraftable vessels and may potentially increase distal run-off when applied in coronary bypass surgery.
TGF-β Requires CTLA-4 Early after T Cell Activation to Induce FoxP3 and Generate Adaptive CD4+CD25+ Regulatory Cells (2006)

Although positive CD28 costimulation is needed for the generation of natural CD4+CD25+ regulatory T cells, we report that negative CTLA-4 costimulation is necessary for generating phenotypically and functionally similar adaptive CD4+CD25+ suppressor cells. TGF-beta could not induce CD4+CD25- cells from CTLA-4(-/-) mice to express normal levels of FoxP3 or to develop suppressor activity. Moreover, blockade of CTLA-4 following activation of wild-type CD4+ cells abolished the ability of TGF-beta to induce FoxP3-expressing mouse suppressor cells. TGF-beta accelerated expression of CTLA-4, and time course studies suggested that CTLA-4 ligation of CD80 shortly after T cell activation enables TGF-beta to induce CD4+CD25- cells to express FoxP3 and develop suppressor activity. TGF-beta also enhanced CD4+ cell expression of CD80. Thus, CTLA-4 has an essential role in the generation of acquired CD4+CD25+ suppressor cells in addition to its other inhibitory effects. Although natural CD4+CD25+ cells develop normally in CTLA-4(-/-) mice, the lack of TGF-beta-induced, peripheral CD4+CD25+ suppressor cells in these mice may contribute to their rapid demise.
Reduction of the N‐type calcium current by noradrenaline in neurones of rabbit vesical parasympathetic ganglia. (1990)

1. Intracellular and single-electrode voltage-clamp recordings were made from neurones of vesical parasympathetic ganglia (VPG) isolated from the rabbit urinary bladder. 2. Noradrenaline (NA, 0.5-5 microM) shortened the duration of the action potentials and depressed the amplitudes of both spike after-hyperpolarization and after-current. 3. Voltage-dependent calcium currents (ICa) were recorded by using microelectrodes filled with 2 M-caesium chloride in a superfusing solution containing tetraethylammonium (TEA, 50 mM) and tetrodotoxin (TTX, 500 nM). Noradrenaline (0.5-5 microM) depressed both the ICa and the tail current evoked by depolarizing voltage jumps from -100 to -50 mV to -30 to +20 mV. 4. Substitution of barium for calcium also produced an inward current (IBa) with no obvious tail current. Noradrenaline (1 microM) reduced the magnitude of the IBa without affecting the voltage dependence of the current-voltage relationship for IBa. 5. Yohimbine (1 microM), but not prazosin (1 microM) or propranolol (1 microM), antagonized the NA-induced inhibition of the IBa. UK 14304, a potent alpha 2-adrenoceptor agonist, mimicked NA in depressing the IBa. 6. The transient low-threshold (T), the transient high-threshold (N) and the slowly inactivating high-threshold (L) calcium currents co-existed in VPG neurones. 7. Noradrenaline reduced the IBa evoked at clamp potentials more positive than -20 mV from holding potentials near the resting membrane potential (-70 to -50 mV). Under these conditions, the IBa consisted primarily of N- and L-current components. In contrast, NA had no effect on the isolated T- and L-currents. It is concluded that NA selectively inhibits the N-type calcium channels by an action at alpha 2-adrenoceptors in the rabbit VPG neurones.
Inactivation of 3-Hydroxy-3-methylglutaryl-CoA Synthase and Other Acyl-CoA-Utilizing Enzymes by 3-Oxobutylsulfoxyl-CoA (1997)

3-Oxobutylsulfoxyl-CoA has been produced by oxidation of S-3-oxobutyl-CoA, the thioether analog of acetoacetyl-CoA. Avian hydroxymethylglutaryl-CoA (HMG-CoA) synthase is inactivated by oxobutylsulfoxyl-CoA in a time-dependent fashion. Protection against inactivation is afforded by the substrate, acetyl-CoA, suggesting that inactivation involves modification of the enzyme's active site. Pretreatment of HMG-CoA synthase with the inactivator blocks the enzyme's ability to form Michaelis and acetyl-S-enzyme intermediates, supporting the hypothesis that modification is active-site directed. Incubation of enzyme with oxobutylsulfoxyl-[32P]CoA followed by precipitation with trichloroacetic acid indicates that inactivation correlates with stoichiometric formation of a covalent adduct between enzyme and a portion of the inactivator that includes the CoA nucleotide. The observation of reagent partitioning suggests that HMG-CoA synthase catalyzes conversion of oxobutylsulfoxyl-CoA into a reactive species that modifies the protein. Treatment of inactivated enzyme with DTT or other mercaptans restores enzyme activity and reverses the covalent modification with release of CoASH. Oxobutylsulfoxyl-CoA inactivates beta-ketothiolase and HMG-CoA lyase in a process that is also reversed by DTT. These three enzymes all contain active site cysteines, suggesting that inactivation results from disulfide formation between a cysteine and the CoA moiety of the inhibitor. The data are consistent with the hypothesis that enzymatic cleavage of oxobutylsulfoxyl-CoA results in the transient formation of a sulfenic acid derivative of CoA which subsequently reacts to form a stable disulfide linkage to protein.
Nonenzymatic glycosylation of poly-l-lysine: A new tool for targeted gene delivery (1994)

The basic approach in targeted gene delivery relies on the formation of a complex between a vector and a molecule that will be selectively internalized by the target cells. In the case of hepatocytes, asialoglycoproteins are convenient targeting molecules because of the high affinity and avidity of the hepatocyte galactose receptor. In this system, poly-L-lysine is cross-linked to an asialoglycoprotein, and the resulting conjugate is complexed with the expression vector (DNA). The electrostatic binding between DNA and poly-L-lysine-asialoglycoprotein ensures delivery of the intravenously injected complex to the liver, where it is subjected to endocytosis by hepatocytes. However, the poly-L-lysine-asialoglycoprotein complexes tend to be unstable, of limited solubility and of fixed carbohydrate content. For these reasons we searched for a simpler alternative. We exploited the known capacity of reducing sugars to be reductively coupled to the epsilon-amino groups in proteins and used lactose to obtain poly-L-lysine with "exposed" galactose. Glycosylation with sodium cyanoborohydride at high pH in borate buffer is a simple, reproducible procedure. The "lactosylated" poly-L-lysine has proved very stable, highly soluble and easily bound to plasmids. In a set of experiments we compared the asialofetuin-poly-L-lysine vector complexes with lactosylated poly-L-lysine vector complexes by transfecting hepatoma cells (HepG2) in culture. For these experiments we used a pRc/cytomegalovirus eukaryotic expression vector containing a mutant TGF-beta 1 complementary DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Kernel Flux: a whole-head 432-magnetometer optically-pumped magnetoencephalography (OP-MEG) system for brain activity imaging during natural human experiences (2021)

MEG based on optically-pumped magnetometry (OP-MEG) operates with miniaturized, wearable insulation, in contrast to massive cryogenic dewars for SQUID-MEG, and allows placement of the sensors close to the scalp. This allows more natural head motion during data recording and localized signal quality comparable to, or surpassing, SQUID-MEG. However no OP-MEG system to date has offered full-head coverage with dense sensor packing, and existing systems - as with SQUID-MEG - require the subject to be sealed in a multilayer, passively-shielded vault in order to suppress ambient magnetic fields. Here we present Kernel Flux, which overcomes these limitations. Kernel Flux uses a collection of alkali vapor sensors in a unique array architecture to directly detect the magnetic fields generated by collective neural activity in the brain, while allowing for comfortable head motion. Each Kernel Flux OP-MEG system was designed from the ground up to work as an integrated system optimized around the user's experience, with relevance to natural home and office contexts.
Volatilisation of ferrocene from ionic liquids: kinetics and mechanism (2011)

The evaporation of dissolved ferrocene from non-volatile ionic liquids under a flow of nitrogen gas has been monitored voltammetrically and modelled mathematically. The rate of volatilisation was found to depend on the surface tension of the ionic liquid, and a model is presented.