Miracle-dz/UniFAR-FTUs huggingface dataset:
ESR studies on the production of reactive oxygen intermediates by rat liver microsomes in the presence of NADPH or NADH.

Experiments were carried out using spin-trapping ESR spectroscopy to evaluate in a quantitative and kinetic manner the production of reactive oxygen intermediates by rat liver microsomes. Comparisons between the effectiveness of NADH and that of NADPH in catalyzing microsomal generation of reactive oxygen intermediates were made. Superoxide production was determined by assaying the generation of superoxide dismutase-sensitive stable nitroxyl radicals formed from 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine. Identical spectra were produced when microsomes were incubated with NADH or NADPH; reaction rates were linear for at least 10 min of reaction and were about three- to fourfold greater with NADPH. In the presence of iron, microsomes catalyze the production of hydroxyl radical during electron transfer. Initial experiments utilizing 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) as the spin-trapping agent proved unsatisfactory for the microsomal system as adequate kinetics could not be determined in view of the rapid decay of the DMPO-OH adduct, as well as secondary adducts such as DMPO-CH3 or DMPO-hydroxyethyl (HER). The spin-trapping agent alpha-[4-pyridyl-1-oxide]-N-tert-butylnitrone (POBN) was evaluated. POBN-OH adducts were somewhat more stable but also rapidly decayed after 2 to 3 min. However, production of POBN-CH3 and POBN-HER adducts was proportional to that of microsomal protein, increased with time over a 5- to 15-min period, and then was relatively stable. The redox cycling agent paraquat increased POBN-HER adduct formation twofold. Formation of the adduct with either NADH or NADPH required an iron catalyst and did not occur in the presence of the iron chelator desferrioxamine. Ferric EDTA was most reactive in catalyzing production of the adduct, ferric DTPA was 60 to 70% as effective, and ferric ATP was 20 to 30% as effective as ferric EDTA, with both reductants. Irrespective of the iron complex, rates of POBN-HER formation with NADH were about 70% those of NADPH. Formation of the adduct was inhibited by catalase, mannitol, and GSH, but not superoxide dismutase. These experiments support the usefulness of POBN plus ethanol for kinetic studies on the production of . OH by microsomes and validate that microsomes in the presence of an iron catalyst generate . OH not only with NADPH as cofactor, but also with NADH.
Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics

Significance Therapeutic antibodies of the immunoglobulin G (IgG) isotype show a pharmacokinetic (PK) profile that is strongly mediated by the interaction with the neonatal Fc receptor (FcRn). Therefore, modulating the FcRn–IgG interaction allows altering PK characteristics of therapeutic antibodies. So far, engineering the crystallizable fragment (Fc) is known to affect PK, and, although the influence of the antigen binding fragment (Fab) on FcRn interactions has been reported, the underlying mechanism remains unknown. Here, we demonstrate that the charge distribution in the distal variable fragment (Fv) of IgGs is involved in excessive binding to the FcRn, thereby reducing FcRn-dependent terminal half-lives in vivo. These findings contribute to a better understanding of the FcRn–IgG interaction. Here, we investigated the influence of the variable fragment (Fv) of IgG antibodies on the binding to the neonatal Fc receptor (FcRn) as well as on FcRn-dependent pharmacokinetics (PK). FcRn plays a key role in IgG homeostasis, and specific manipulation in the crystallizable fragment (Fc) is known to affect FcRn-dependent PK. Although the influence of the antigen-binding fragment (Fab) on FcRn interactions has been reported, the underlying mechanism is hitherto only poorly understood. Therefore, we analyzed the two IgG1 antibodies, briakinumab and ustekinumab, that have similar Fc parts but different terminal half-lives in human and systematically engineered variants of them with cross-over exchanges and varied charge distribution. Using FcRn affinity chromatography, molecular dynamics simulation, and in vivo PK studies in human FcRn transgenic mice, we provide evidence that the charge distribution on the Fv domain is involved in excessive FcRn binding. This excessive binding prevents efficient FcRn–IgG dissociation at physiological pH, thereby reducing FcRn-dependent terminal half-lives. Furthermore, we observed a linear correlation between FcRn column retention times of the antibody variants and the terminal half-lives in vivo. Taken together, our study contributes to a better understanding of the FcRn–IgG interaction, and it could also provide profound potential in FcRn-dependent antibody engineering of the variable Fab region.
Between-school variation in physical activity, aerobic fitness, and organized sports participation: A multi-level analysis

Abstract A large proportion of a child's day is spent at school interacting with certain physical surroundings, teachers, and school friends. Thus, schools could have a marked impact on establishing physical activity habits. The aim of the present study was to assess between-school variation in physical activity, aerobic fitness, and organized sports participation. Altogether, we tested 1766 nine- and fifteen-year-old children attending 242 school classes at 35 different schools in Denmark in 1997–2003. The intra-class correlation coefficient (ICC) for objectively assessed physical activity ranged between 0.06 and 0.18 depending on the dimension of physical activity and the time considered (i.e. school time vs. leisure time). For aerobic fitness, an ICC of 0.10 was observed, whereas that for organized sports participation ranged between 0.01 and 0.10 depending on the age group. Studying between-school variation in physical activity provides information about the extent to which children adjust their physical activity habits according to the social and environmental circumstances that they share, and helps to plan future school-based physical activity studies, especially in terms of sample size and power calculation.
DHEA in elderly women and DHEA or testosterone in elderly men.

BACKGROUND Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown. METHODS We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. RESULTS As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects. CONCLUSIONS Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).
Papel das competências técnico-organizacionais na estratégia organizacional: evidências de cinco organizações não governamentais no Rio de Janeiro (1996-2004)

Muito embora haja uma vasta literatura sobre as implicacoes das competencias tecnico-organizacionais para o desempenho de organizacoes, varias destas estao concentradas no ambiente industrial. Ao mesmo tempo, nao existem muitos estudos sobre estas competencias em organizacoes nao governamentais (ONGs). Este artigo examina as implicacoes da competencia tecnico-organizacional para o aprimoramento de desempenho de ONGs sob a perspectiva de estrategia baseada em competencias dinâmicas. O estudo subjacente a este artigo baseia-se numa amostra de cinco organizacoes no Rio de Janeiro e cobre o periodo de 1996 a 2004. A pesquisa faz uso de evidencias empiricas de primeira mao colhidas a base de trabalho de campo e examinadas a luz de um modelo que identifica nove dimensoes de competencias tecnico-organizacionais. O estudo encontrou que as ONGs que fazem esforcos explicitos para o aprimoramento destas dimensoes, apresentam melhores indicadores de desempenho. Portanto a perspectiva de competencias dinâmicas mostrou-se fortemente viavel para explicar diferencas de desempenho tambem neste tipo de organizacoes. Palavras-chave: Estrategia. Competencias. ONG. Desempenho. Tecnico-organizacional.
Optimal alignment for enzymatic proton transfer: Structure of the Michaelis complex of triosephosphate isomerase at 1.2-Å resolution

In enzyme catalysis, where exquisitely positioned functionality is the sine qua non, atomic coordinates for a Michaelis complex can provide powerful insights into activation of the substrate. We focus here on the initial proton transfer of the isomerization reaction catalyzed by triosephosphate isomerase and present the crystal structure of its Michaelis complex with the substrate dihydroxyacetone phosphate at near-atomic resolution. The active site is highly compact, with unusually short and bifurcated hydrogen bonds for both catalytic Glu-165 and His-95 residues. The carboxylate oxygen of the catalytic base Glu-165 is positioned in an unprecedented close interaction with the ketone and the α-hydroxy carbons of the substrate (C… O ≈ 3.0 Å), which is optimal for the proton transfer involving these centers. The electrophile that polarizes the substrate, His-95, has close contacts to the substrate's O1 and O2 (N… O ≤ 3.0 and 2.6 Å, respectively). The substrate is conformationally relaxed in the Michaelis complex: the phosphate group is out of the plane of the ketone group, and the hydroxy and ketone oxygen atoms are not in the cisoid configuration. The ɛ ammonium group of the electrophilic Lys-12 is within hydrogen-bonding distance of the substrate's ketone oxygen, the bridging oxygen, and a terminal phosphate's oxygen, suggesting a role for this residue in both catalysis and in controlling the flexibility of active-site loop.
Expression of Estrogen Receptor β in Colon Cancer Progression

Colon cancer is the most frequent neoplasia of the intestine. This pathology is the third highest cause of death from cancer with 430,000 deaths globally per year. Estrogen has also been implicated in the development and progression of colon cancer. Also sex-specific differences have been suggested to be involved in the process. Previous studies have shown the estrogen β receptor to be the dominant receptor type in normal colonic tissue and its down-regulation along with the progression of colorectal cancer. The presence of estrogen receptors and products of estrogen-related genes in the colon suggests that estrogens have direct effects on the colonic tissue. However, the specific effect of estrogens on a normal colon and the role in the colon carcinogenesis are far from clear. The aim of this study is to analyze by real-time polymerase chain reaction, the relative quantitative expression of the estrogen receptors β, β1, β2, and β5 in colon adenocarcinomas and to compare this expression with the respective in normal tissues. Moreover, we evaluate a possible correlation between estrogen's receptor expressions and disease stages. Normal tissues show estrogen receptor β expression greater than pathologic tissues and the estrogen receptor β result as most expressed in the lower disease stages.
Comparison of resistor matching performance of polysilicon films in a CMOS process

Matched pairs or arrays of resistive elements are an important aspect of many analog and mixed signal semiconductor circuit designs. Such structures are often implemented using the polysilicon layers in a typical CMOS process. In many processes, there are two or more such layers at the disposal of the designer. These typically have differing resistivity characteristics and matching performance. This paper examines the resistance matching characteristics of the polysilicon layers on a commercial CMOS process. The study encompasses both wafer-to-wafer and die-to-die variations, and presents models to describe the behavior. Using these models, conclusions are drawn regarding the appropriate layer to use to minimize the silicon area for target values of resistance and matching.
Unified Tuning of PID Load Frequency Controller for Power Systems via IMC

A unified PID tuning method for load frequency control (LFC) of power systems is discussed in this paper. The tuning method is based on the two-degree-of-freedom (TDF) internal model control (IMC) design method and a PID approximation procedure. The time-domain performance and robustness of the resulting PID controller is related to two tuning parameters, and robust tuning of the two parameters is discussed. The method is applicable to power systems with non-reheated, reheated, and hydro turbines. Simulation results show that it can indeed improve the damping of the power systems. It is shown that the method can also be used in decentralized PID tuning for multi-area power systems.
Transmission of Force Sensation by Micro-Macro Bilateral Control with Respect to Standardized Modal Space

This paper proposes novel micro-macro bilateral control architecture with respect to standardized modal space. In bilateral control, force control and position control must be realized simultaneously in the same real axis. In this paper, force control is achieved in virtual common mode space and position control is attained in virtual differential mode space respectively. In the modal space, common mode and differential mode are orthogonal. Thus, force control and position control are able to be realized simultaneously. Additionally, the standardization matrix that harmonizes the standard of macro master system with the standard of micro slave system in the modal space is proposed as well. With the proposed method, the transmission of force sensation from the real micro environment is achieved. To verify the validity of the proposed method, experimental results are shown.
Autoxidation of Insect Lipids: Inhibition on the Cuticle of the American Cockroach

The major hydrocarbon, cis, cis-6,9-heptacosadiene, of Periplaneta americana cuticles and oothecae solidifies in air by autoxidation. The reaction resembles the autoxidation of other dienes by known free radical mechanisms and yields stearic acid, stearal, hexanoic acid, and hexanal. On the cuticle, autoxidation is inhibited by polyhydric phenols.
Accentuation of optical coherence tomography angiography projection artefacts on hyper‐reflective retinal layers

O ptical coherence tomography angiography (OCTA) has been gaining attention with its non-invasive ability to imageocular vessels in adepthresolved manner based on flow. However, it is critical to be aware of potential artefacts when interpreting images. Spaide and colleagues recently described image artefacts observed on OCTA, establishing a common vocabulary (Spaide et al. 2015). Projection artefacts are by far the most common and are usually seen across all retinal layers but more prominently at the level of the hyper-reflective retinal pigment epithelium (RPE), where some of the reflected light travels back through the overlying retinal vessels and simulates blood flow. We hereby describe a case of paracentral acute middle maculopathy (PAMM) where there was accentuation of OCTA projection artefact over areas that corresponded to hyper-reflectivity on en face OCT scans. Inner nuclear layer hyper-reflectivity is the characteristic feature of PAMM lesions on cross-sectional (Rahimy & Sarraf 2014) and en face OCT (Nemiroff et al. 2015; Sridhar et al. 2015). The presented case is a patient with presumed branch retinal vein occlusion and fern-like PAMM lesions distributed around venules (Sridhar et al. 2015) (Fig. 1). Focal accentuation of the superficial vascular flow can be appreciated over the areas of middle retinal hyperreflectivity (yellow arrowheads), which also cause shadowing and obscuration at the deeper slabs (red arrowheads). To further demonstrate this in a normal eye, a second case is presented in Fig. 2. This depicts eccentric Henle’s fibre layer (HFL) reflectivity due to slight temporal displacement of the entry beam. Although the foveal anatomy has not changed, there is an apparent tilt to the horizontal B-scan because of unequal optical path lengths (Lujan et al. 2011). This has resulted in hyper-reflectivity of HFL relative to the outer nuclear layer nasal to the fovea and hyporeflectivity of HFL temporal to the fovea, where distinct demarcations among the outer nuclear layer, HFL, and inner plexiform layer
Characterization of 3D electromagnetic scattering from PEC man-made target above rough surface

Simulation and processing of radar echoes from objects above various terrains are of great importance in applications including remote sensing and oceanography. This paper firstly gives a short literature review on the methods for composite electromagnetic scattering from both target and rough/ocean surface. Then attention is focused on modeling 3D electromagnetic scattering from large target (such as tank, missile, ship) above rough surface (including ocean surface) based on shooting and bouncing ray (SBR) method. SBR method combines geometrical optics (GO) and physical optics (PO), showing the ability to calculate scattering from electrically large complex targets with much less computer resource than its numerical counterparts. In this paper, some numerical examples are given to demonstrate the efficiency and power of SBR. Scattering, especially backscattering properties of large targets above rough and ocean surface of different types are presented.
Renal Protection by Ischemic Preconditioning Is Associated with p50/p50 Homodimers

Background: Although recent studies indicate that renal ischemia preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protection mechanism is still unknown. It has been widely recognized that the activity of nuclear factor-ĸB (NF-ĸB) is altered upon I/R injury. However, few studies have focused on the compositional change of NF-ĸB complexes. In the current study, we observed different NF-ĸB dimers in I/R and IPC, and postulated that p50 homodimers might represent the predominant NF-ĸB activation in renal IPC. Methods: 24 male SD rats were treated with a sham operation, I/R or IPC. While the right kidney was removed in all animals, I/R was induced by left renal artery clamping for 45 min, and IPC was induced by left renal artery clamping for 2 min, reperfused for 5 min, and repeated for 3 cycles before 45 min occlusion. After 24 h of reperfusion, we assessed NF-ĸB activities, composition of NF-ĸB, and expression of IL-18. Results: Compared to the I/R group, NF-ĸB activity decreased significantly in the IPC group. Supershift assays were then performed to examine the NF-ĸB subunits in the binding complexes. In both the I/R and IPC groups, the composition of NF-ĸB contained p65 and p50. The densities of these two supershift bands were almost equivalent in the I/R group, suggesting the NF-ĸB composition was p50/p65 dimers. However, the densities of p50 bands were more than twice that of p65 in the IPC group and the levels of Bcl-3 increased in parallel in these rats, suggesting that p50/p50 homodimers might dominate the NF-ĸB activities in renal IPC. Finally, the expression of IL-18, a marker of acute kidney injury, was significantly increased in the area of tubulointerstitium in the I/R group and attenuated in the IPC group. Conclusion: In conclusion, our investigation suggests that: (1) the general activity of NF-ĸB is attenuated in IPC kidneys, and (2) the remaining activation of NF-ĸB is dominated with p50/p50 homodimer. Both of these effects might subsequently downregulate IL-18 expression, as well as provide renal protective effects of IPC. Though we focused on the phenomenological observations in this study, the detailed mechanism is still to be determined.
Von Willebrand Factor and Mitral Valve Prolapse

Summary The levels of von Willebrand factor (vWF: Ag) were measured in 27 patients with mitral valve prolapse (MVP) and compared to 27 age matched controls. Decreased levels of vWF:Ag (<80%) were found in 59% (16/27) of those with MVP compared to only 7% (2/27) of the controls (p <0.001). Mean vWF: Ag levels were also significantly lower in those with MVP (68 ± 30% versus 100 ± 23%, p <0.001). In those with MVP and congestive heart failure secondary to ruptured chordae tendineae, however, the mean level of vWF:Ag was not significantly different from control values (95 ± 32). There was an increased incidence of recurrent nose bleeds in those with MVP and low levels of vWF: Ag. We conclude that there is a relationship between MVP and low levels of vWF:Ag which may explain the increased incidence of epistaxis in such patients. Increased release of vWF: Ag in those with MVP and concomitant congestive heart failure may account for the normal levels found in this subgroup.
Urinary excretion of leukotriene E4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and histamine in asthmatics.

In vivo production of thromboxane (TX) A2 and the cysteinyl-containing leukotrienes (LT) C4, D4, and E4 in correlation to airway responses was studied. Bronchial provocation with specific allergen in atopic asthmatics was followed by a significant increase in urinary concentration of immunoreactive LTE4 (34 +/- 6 before versus 56 +/- 7 ng/mmol creatinine after allergen challenge; n = 5) and 11-dehydro-TXB2 (164 +/- 29 versus 238 +/- 25 ng/mmol creatinine). In the presence of the leukotriene-antagonist ICI-204,219, which significantly increased the PD20 for allergen, the increment in urinary excretion of LTE4 was even higher (60 +/- 8 versus 288 +/- 128 ng/mmol creatinine; n = 5). In contrast, provocation with histamine (n = 5) did not provoke release of leukotrienes or thromboxane, nor was inhalation of LTD4 (n = 7) associated with increased urinary concentration of 11-dehydro-TXB2. Furthermore, bronchoconstriction induced by inhalation of lysine-aspirin in aspirin-sensitive asthmatics (n = 4) was followed by increased levels of LTE4 in the urine, whereas the levels of 11-dehydro-TXB2 remained the same. Finally, the basal levels of LTE4 in the urine of nine aspirin-sensitive asthmatics were elevated as compared with 15 other asthmatics (112 +/- 54 versus 38 +/- 20 ng/mmol creatinine; p less than 0.001). The findings support that the cysteinyl-leukotrienes are potential mediators of allergen-induced asthma and that the release of LTE4 and 11-dehydro-TXB2 into the urine appeared to be a direct and dose-dependent effect of the antigen-antibody reaction. (ABSTRACT TRUNCATED AT 250 WORDS)