Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of block‐periodized exercise training on bone and coronary heart disease risk factors in early post‐menopausal women: a randomized controlled study

The purpose of this 12 month randomized exercise intervention was to determine the effect of a block‐periodized multipurpose exercise program on bone mineral density (BMD) and parameters of the metabolic syndrome (MetS) in early post‐menopausal women. Eighty‐five subjects (52.3 ± 2.4 years) living in the area of Erlangen (Germany) were randomly assigned into an exercise (EG, n=43) or a wellness‐control group (CG: n=42). The EG performed a periodized multipurpose exercise program with 4–6‐week blocks of high‐intensity bone‐specific exercise intermitted by 10–12 weeks of exercise dedicated to increase endurance and reduce cardiac and metabolic risk factors. The CG performed a low‐volume/low‐intensity “wellness” program to increase well‐being. After 12 months, significant exercise effects were observed for the lumbar spine (LS) BMD as assessed by quantitative computed tomography [total BMD (EG: −0.3 ± 2.1% vs CG: −2.1 ± 2.2%, P=0.015); trabecular BMD (EG: −0.7 ± 3.4% vs CG: −4.7 ± 4.9%, P=0.001) and dual‐energy x‐ray absorptiometry (DXA) (EG: −0.1 ± 2.2% vs CG: −2.0 ± 2.0%, P=0.002)]. However, no significant effects were observed for total hip BMD as assessed by DXA (P=0.152). Although all MetS parameters were favorably affected among the EG, only the effect for waist circumference was significant. In summary, short periods of bone‐specific intervention embedded in longer periods of exercises dedicated to improve cardiovascular and metabolic risk factors positively affected BMD at the LS.
‘Dual Positivity’ for Neural Tube Defects and Down Syndrome at Maternal Serum Screening: Gestational Outcome

Objective: To evaluate the gestational outcome of pregnancies screen-positive for both neural tube defects (NTD) and Down syndrome (DS) (‘dual positivity’). Methods: Among 10,667 mid-trimester women screened for DS and NTD with α-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG), delivered up to July 1996, we have selected cases with both an unexplained AFP value ≥2.5 multiples of median (MoM) and a DS risk ≥1:250. All these pregnant women were managed with amniocentesis and/or CVS, ultrasound scans, and Doppler velocimetry. We have collected all data about the gestations with ‘dual positivity’ and no obvious explanation for these findings (cases with fetal malformations related to raised AFP). Results: Twelve women (1.1:1,000) showed unexplained ‘dual positivity’. Abnormal karyotypes were found in 3 fetuses, and pregnancies were terminated: there were 2 triploidies with partial hydatiform mola, and 1 DS. In 9 cases the fetal karyotype was normal, but a confined placental trisomy 16 was found in 4. Of the 9 continuing gestations, 8 displayed fetal growth retardation (FGR). One gestation ended with fetal death at 27 weeks. All 9 fetuses were morphologically normal, and 8 were small for gestational age. Conclusions: ‘Dual positivity’ at NTD/DS screening may anticipate pregnancy complications. The finding of trisomy 16 confined to the placenta and FGR in 4 cases suggests that at least some fetuses with growth restriction may suffer from a distinct placental disease. Maternal serum screening may have implications different from DS and NTD, as demonstrated by the 2 cases with triploidy and incomplete hydatiform mola, the 4 cases with placental trisomy 16, and the 4 cases of FGR of the 5 fetuses without chromosome abnormalities. As the pathologic outcome of these pregnancies is more important than the mere serum screening results, we feel that these cases need a strict work-up, including CVS, amniocentesis and ultrasound studies to better address the obstetrical management.
Modified Low Density Lipoprotein Enhances the Secretion of Bile Salt-stimulated Cholesterol Esterase by Human Monocyte-Macrophages

Reverse transcriptase-polymerase chain reaction was used to study the biosynthesis of two different cholesteryl ester hydrolases by human and mouse macrophages. Oligonucleotide primers for bile salt-stimulated cholesterol esterase yielded positive reactions with RNA isolated from human peripheral blood monocytes, monocyte-derived macrophages, the human monocytic THP-1 cells, and phorbol ester-induced THP-1 macrophages. In contrast, oligonucleotide primers for hormone-sensitive lipase yielded positive reactions only with RNA isolated from non-differentiated human THP-1 monocytic cells and peripheral blood monocytes, but not those obtained from differentiated THP-1 macrophages or monocyte-derived macrophages. Thus, while human monocytes were capable of synthesizing both enzymes, human macrophages synthesized only bile salt-stimulated cholesterol esterase and not the hormone-sensitive lipase. The synthesis of bile salt-stimulated cholesterol esterase by human macrophages was confirmed by detection of bile salt-stimulated cholesteryl ester hydrolytic activity in conditioned media of differentiated THP-1 cells and human peripheral blood monocyte-derived macrophages. Moreover, incubating human macrophages with oxidized low density lipoprotein (LDL) or acetylated LDL increased bile salt-stimulated cholesterol esterase activity in the conditioned media of these cells. These results with human macrophages were contrasted with results of studies with mouse macrophages, which showed the presence of hormone-sensitive lipase mRNA but not the bile salt-stimulated cholesterol esterase mRNA. Taken together, these results demonstrated species-specific differences in expression of cholesteryl ester hydrolytic enzymes in macrophages. The expression of bile salt-stimulated cholesterol esterase by human macrophages, in a process inducible by modified LDL, suggests a role of this protein in atherogenesis.
Structure and function of conjugative pili: monoclonal antibodies as probes for structural variants of F pili

The lac-tra operon fusion plasmid pTG801 contains the known F plasmid DNA transfer (tra) genes required by Escherichia coli to elaborate functional F pili (T. Grossman and P. M. Silverman, J. Bacteriol. 171:650-656, 1989). Here, we show that these pili are actually structural variants of normal F pili and that the F plasmid must contain additional genes that affect pilus structure and function. We confirmed a previous report that two monoclonal antibodies that recognize epitopes at and near the amino terminus of F pilin do not decorate the sides of normal F pili, as determined by immunogold electron microscopy. However, both antibodies laterally decorated pTG801 pili. The epitope for one of the antibodies has been shown to include the amino-terminal acetyl group of F pilin, which must therefore also be present on pTG801 pilin. Normal antibody staining was restored to pTG801 pili when cells contained, in addition to pTG801, the compatible plasmid pRS31, which must therefore include at least one gene affecting F-pilus structure. One candidate, traD, was excluded as the sole such gene, since traD+ derivatives of a pTG801 strain still elaborated pili that could be laterally decorated with antibody. Moreover, although traD alone restored RNA bacteriophage R17 infectivity to pTG801 cells, as expected, it did not mimic pRS31 in restoring to pTG801 pili other characteristics of normal F pili. We conclude that pRS31 contains as yet uncharacterized genes required for elaboration of structurally normal F pili. Finally, we identified vesicular material, especially abundant in cultures of pTG801 transformants, that stained heavily with the anti-F-pilin monoclonal antibodies. This material may reflect the inner membrane pool of F pilin.
Electrogenic K+ transport by the Na+–K+ pump in rat cardiac ventricular myocytes

1 The involvement of electrogenic reaction steps in K+ transport by the Na+,K+‐ATPase was determined in rat cardiac ventricular myocytes using whole‐cell patch clamp techniques. 2 Under K+–K+ exchange conditions and in the presence of extracellular K+ or Tl+ at concentrations that stimulated submaximal levels of steady‐state Na+,K+‐ATPase activity, ouabain‐sensitive transient currents were observed during (‘on’) and after (‘off’) step changes in membrane potential (Vm). 3 The quantity of charge moved during the transient currents depended, in a saturable manner, on the magnitude of the voltage step. Maximal ouabain‐sensitive ‘on’ and ‘off’ charges were calculated to be 9.6 ± 0.9 and 9.1 ± 0.4 fC pF−1 (n= 4), respectively, with an effective valency of 0.48 ± 0.07 (n= 7). 4 Kinetics of the transient currents were independent of Vm and Tlo+ at positive potentials, but became more rapid at increasingly negative Vm values in an ion concentration‐dependent fashion. 5 These data demonstrate that electrogenic steps participate in K+ transport by the Na+,K+‐ATPase and that the electrogenic step is extracellular ion binding. 6 The temperature‐and Vm‐dependent properties of transient charge movements were compared under K+–K+ and Na+–Na+ exchange conditions. The data suggest that extracellular K+ and Na+ binding occur at different sites in the enzyme or to different enzyme conformations. The sum of the effective valencies, 1.14 ± 0.12, demonstrates that the electrogenicity of extracellular ion binding can explain the Vm dependence of ion transport by the Na+,K+‐ATPase.
Photophysical and Phototoxic Properties of the Antibacterial Fluoroquinolones Levofloxacin and Moxifloxacin

Two antibacterial fluoroquinolones, levofloxacin and moxifloxacin, were investigated to evaluate their photophysical properties and to explore the mechanism of their phototoxicity. Photophysical experiments were carried out in aqueous solution by stationary and time‐resolved fluorimetry, and by laser flash photolysis, to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed upon irradiation. The results obtained show that levofloxacin is able to photosensitize red blood cell lysis in an oxygen‐independent way and induce a high decrease in cell viability after UVA irradiation, although to a lesser degree than the racemic mixture ofloxacin. Moxifloxacin, which is an 8‐MeO‐substituted fluoroquinolone, is less phototoxic than the other compounds. Cellular phototoxicity was inhibited by the addition of superoxide dismutase, catalase, and free radical and hydroxyl radical scavengers (BHA, GSH, mannitol, and DMTU), indicating the involvement of superoxide anion and/or a radical mechanism in their cytotoxicity. A good correlation was observed between lipid peroxidation, protein photodamage, and cellular phototoxicity, indicating that test compounds exert their toxic effects mainly in the cellular membrane. Experiments carried out on pBR322 DNA show that these derivatives do not significantly photocleave DNA directly, but single‐strand breaks were evidenced after treatment of photosensitized DNA by two base‐excision‐repair enzymes, and Endo III.
Spontaneous depolarization wave in the mouse embryo: origin and large‐scale propagation over the CNS identified with voltage‐sensitive dye imaging

Spontaneous embryonic movements, called embryonic motility, are produced by correlated spontaneous activity in the cranial and spinal nerves, which is driven by brainstem and spinal networks. Using optical imaging with a voltage‐sensitive dye, we have revealed previously that this correlated activity is a widely propagating wave of neural depolarization, which we termed the depolarization wave. We have observed in the chick and rat embryos that the activity spread over an extensive region of the CNS, including the spinal cord, hindbrain, cerebellum, midbrain and forebrain. One important consideration is whether a depolarization wave with similar characteristics occurs in other species, especially in different mammals. Here, we provide evidence for the existence of the depolarization wave in the mouse embryo by showing that the widely propagating wave appeared independently of the localized spontaneous activity detected previously with Ca2+ imaging. Furthermore, we mapped the origin of the depolarization wave and revealed that the wave generator moved from the rostral spinal cord to the caudal cord as development proceeded, and was later replaced with mature rhythmogenerators. The present study, together with an accompanying paper that describes pharmacological properties of the mouse depolarization wave, shows that a synchronized wave with common characteristics is expressed in different species, suggesting fundamental roles in neural development.
Generation of coherent mosaic animations: enhancement and evaluation of temporal coherence

Although the creation static mosaic‐like images from non‐mosaic input has been studied, satisfactory methods to maintain and evaluate the temporal coherence of tiles for mosaic animations have remained elusive. Here, we describe a method that successfully generates mosaic animations from videos by applying a temporally and spatially coherent tile‐arrangement technique. We arrange tiles on the basis of the feature lines extracted from video input. We then animate the tiles along the motion of the video, add and delete tiles to preserve the tile density, and smooth tile color via frames. Finally, we propose indices to evaluate the temporal coherence of video‐based animations, and show that our animations are temporally coherent. Copyright © 2012 John Wiley & Sons, Ltd.
Protein-protein-interaction Network Organization of the Hypusine Modification System

Hypusine modification of eukaryotic initiation factor 5A (eIF-5A) represents a unique and highly specific post-translational modification with regulatory functions in cancer, diabetes, and infectious diseases. However, the specific cellular pathways that are influenced by the hypusine modification remain largely unknown. To globally characterize eIF-5A and hypusine-dependent pathways, we used an approach that combines large-scale bioreactor cell culture with tandem affinity purification and mass spectrometry: “bioreactor-TAP-MS/MS.” By applying this approach systematically to all four components of the hypusine modification system (eIF-5A1, eIF-5A2, DHS, and DOHH), we identified 248 interacting proteins as components of the cellular hypusine network, with diverse functions including regulation of translation, mRNA processing, DNA replication, and cell cycle regulation. Network analysis of this data set enabled us to provide a comprehensive overview of the protein-protein interaction landscape of the hypusine modification system. In addition, we validated the interaction of eIF-5A with some of the newly identified associated proteins in more detail. Our analysis has revealed numerous novel interactions, and thus provides a valuable resource for understanding how this crucial homeostatic signaling pathway affects different cellular functions.
The Kv7.2/Kv7.3 Heterotetramer Assembles with a Random Subunit Arrangement*

Background: Kv7.2 and Kv7.3 coassemble to form a heteromeric K+ channel that generates the M-current. Results: Atomic force microscopy (AFM) imaging of Kv7.2/Kv7.3 heteromers in complex with subunit-specific antibodies reveals the channel architecture. Conclusion: The Kv7.2/Kv7.3 heteromer assembles with a random subunit arrangement. Significance: Unusually, heteromeric Kv7 channels have a variable architecture. Voltage-gated K+ channels composed of Kv7.2 and Kv7.3 are the predominant contributors to the M-current, which plays a key role in controlling neuronal activity. Various lines of evidence have indicated that Kv7.2 and Kv7.3 form a heteromeric channel. However, the subunit stoichiometry and arrangement within this putative heteromer are so far unknown. Here, we have addressed this question using atomic force microscopy imaging of complexes between isolated Kv7.2/Kv7.3 channels and antibodies to epitope tags on the two subunits, Myc on Kv7.2 and HA on Kv7.3. Initially, tsA 201 cells were transiently transfected with equal amounts of cDNA for the two subunits. The heteromer was isolated through binding of either tag to immunoaffinity beads and then decorated with antibodies to the other tag. In both cases, the distribution of angles between pairs of bound antibodies had two peaks, at around 90° and around 180°, and in both cases the 90° peak was about double the size of the 180° peak. These results indicate that the Kv7.2/Kv7.3 heteromer generated by cells expressing approximately equal amounts of the two subunits assembles as a tetramer with a predominantly 2:2 subunit stoichiometry and with a random subunit arrangement. When the DNA ratio for the two subunits was varied, copurification experiments indicated that the subunit stoichiometry was variable and not fixed at 2:2. Hence, there are no constraints on either the subunit stoichiometry or the subunit arrangement.
Characterization of the DNA damage recognized by an antiserum elicited against cis-diamminedichloroplatinum (II)-modified DNA.

A series of in vitro and in vivo studies were performed to characterize DNA damage recognized by an antiserum elicited against DNA modified with cis-diamminedichloroplatinum(II) (cisplatin). Adducts determined by the cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) in human blood cell DNA have been shown to correlate well with positive clinical outcome in testicular and ovarian cancer patients receiving platinum drug-based chemotherapy (Reed et al. (1990) Proc. Natl. Acad. Sci., 84; 5024, and Reed et al. (1988) Carcinogenesis, 9, 1909). DNAs from calf thymus, salmon sperm, pBR322 and synthetic oligonucleotides were modified with cisplatin in vitro before or after specific DNA digestion steps to yield adducted samples of known size and/or chemical composition. These cisplatin modified DNAs were assayed by atomic absorption spectrometry (AAS) to assess absolute platinum content, and by ELISA to determine the antiserum specificity. The antiserum recognizes native cisplatin-modified calf thymus DNA, and native oligonucleotides containing intrastrand cis-Pt (NH3)2-d(pGpG) adducts (Pt-GG) and intrastrand cis-Pt (NH3)2-d(pApG) adducts (Pt-AG). Modified plasmid DNA fragments of varying sizes (down to 309 base pairs) are recognized similarly to cisplatin-modified calf thymus DNA. The antiserum does not cross-react with individual Pt-GG or Pt-AG adducts not bound to DNA. In experiments designed to assess the relationship between adduct measured by ELISA and total platinum bound to DNA as measured by AAS, male and female Sprague-Dawley rats were injected i.p. with cisplatin and a dose response for adduct formation was determined in kidney DNA samples. Values obtained by ELISA were substantially lower than those measured by AAS, and the two were directly related in DNA from kidney tissues of rodents but not in DNA from human nucleated blood cells. In rodent samples the ELISA measured a consistent 0.2% of the total DNA-bound platinum determined by AAS, with a correlation coefficient of 0.91. Among 54 blood cell DNA samples from human patients, which gave measurable adduct values in both ELISA and AAS, the ELISA measured a variable fraction (0.2-33.0%) of the total DNA-bound platinum measured by AAS. We conclude that the cisplatin-DNA ELISA measures a three dimensional lesion in DNA that is formed in direct proportion to total DNA-bound platinum in rat kidney, but that in human biological samples, interindividual variability precludes a relationship that conforms to simple mathematical algorithms.
Development of Lipid-Based Nanoparticles for Enhancing the Oral Bioavailability of Paclitaxel

The current research work investigates the potential of solid lipid nanoparticles (SLNs) in improving the oral bioavailability of paclitaxel. Paclitaxel-loaded SLNs (PTX-SLNs) were prepared by modified solvent injection method using stearylamine as lipid, soya lecithin and poloxamer 188 as emulsifiers. SLNs were characterized in terms of surface morphology, size and size distribution, surface chemistry and encapsulation efficiency. Pharmacokinetics and bioavailability studies were conducted in male Swiss albino mice after oral administration of PTX-SLNs. SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The mean particle size of SLNs was 96 ± 4.4 nm with a low polydispersity index of 0.162 ± 0.04 and zeta potential of 39.1 ± 0.8 mV. The drug entrapment efficiency was found to be 75.42 ± 1.5% with a loading capacity of 31.5 ± 2.1% (w/w). Paclitaxel showed a slow and sustained in vitro release profile and followed Higuchi kinetic equations. After oral administration of the PTX-SLNs, drug exposure in plasma and tissues was ten- and twofold higher, respectively, when compared with free paclitaxel solution. PTX-SLNs produced a high mean Cmax (10,274 ng/ml) compared with that of free paclitaxel solution (3,087 ng/ml). The absorbed drug was found to be distributed in liver, lungs, kidneys, spleen, and brain. The results suggested that PTX-SLNs dispersed in an aqueous environment are promising novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral delivery of paclitaxel as observed by in vivo toxicity studies.
Monte Carlo Simulations of High-Performance Implant Free In$_{0.3}$Ga $_{0.7}$As Nano-MOSFETs for Low-Power CMOS Applications

The potential performance of implant free heterostructure In0.3Ga0.7As channel MOSFETs with gate lengths of 30, 20, and 15 nm is investigated using state-of-the-art Monte Carlo (MC) device simulations. The simulations are carefully calibrated against the electron mobility and sheet density measured on fabricated III-V MOSFET structures with a high-kappa dielectric. The MC simulations show that the 30 nm gate length implant free MOSFET can deliver a drive current of 2174 muA/mum at 0.7 V supply voltage. The drive current increases to 2542 muA/mum in the 20 nm gate length device, saturating at 2535 muA/mum in the 15 nm gate length one. When quantum confinement corrections are included into MC simulations, they have a negligible effect on the drive current in the 30 and 20 nm gate length transistors but lower the 15 nm gate length device drive current at 0.7 V supply voltage by 10%. When compared to equivalent Si based MOSFETs, the implant free heterostructure MOSFETs can deliver a very high performance at low supply voltage, making them suitable for low-power high-performance CMOS applications
Completely flat 2D Zn3O2 monolayer with triangle and pentangle coordinated networks

Two-dimensional (2D) materials with strictly planar hyper-coordinated motifs are of great importance in fundamental science and potential applications but extremely rare. Here we theoretically design a novel 2D IIB-VIA inorganic system, namely Zn3O2 monolayer, by comprehensive first-principles computations. This Zn3O2 monolayer is composed from highly symmetrical tri-coordinated oxygen and tetra-coordinated zinc, featuring planar and peculiar triangle and pentangle combined bonded network. The newly predicted Zn3O2 monolayer possesses excellent dynamic and thermal stabilities and is also the lowest-energy structure of its 2D space indicated by particle swarm search, supporting its experimentally synthetic viability. A relatively wide band gap of 4.46 eV means it has potential applications in electronics and optoelectronics. The present findings provide a new field of hyper-coordinated 2D nanomaterials for study.