Miracle-dz/UniFAR-FTUs huggingface dataset:
Antifibrotic effect of Pirfenidone on orbital fibroblasts of patients with thyroid-associated ophthalmopathy by decreasing TIMP-1 and collagen levels.

PURPOSE The aim of this study was to determine the antifibrotic effects of pirfenidone in orbital fibroblasts of patients with thyroid-associated ophthalmopathy (TAO). METHODS The effects of interleukin (IL)-1beta and of fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor (TGF)-beta on the induction of tissue inhibitors of metalloproteinases (TIMP)-1 were assessed in orbital fibroblasts of TAO patients. TIMP-1 protein levels were measured by ELISA and Western blot analyses, and TIMP-1 activity was assessed by reverse zymography. The effect of pirfenidone on TIMP-1 induction in orbital fibroblasts was evaluated with the same methods using dexamethasone as a reference agent. A hydroxyproline assay was used to determine the effect of pirfenidone and dexamethasone on collagen production in orbital fibroblasts, and the tetrazolium-based MTT assay was used to assess pirfenidone cytotoxicity. RESULTS IL-1beta strongly and dose dependently increased the level of active TIMP-1 protein, whereas FGF, PDGF, and TGF-beta did not significantly induce TIMP-1 protein. Pirfenidone was more effective than dexamethasone in inhibiting IL-1beta-induced increases in TIMP-1, reducing TIMP-1 levels to less than those in untreated controls at a minimal concentration (5 mM). Moreover, pirfenidone effectively decreased hydroxyproline levels in orbital fibroblasts, whereas dexamethasone had no effect on hydroxyproline levels. Pirfenidone exhibited no toxicity in orbital fibroblasts at the concentrations used. CONCLUSIONS These results indicate that nontoxic concentrations of pirfenidone have significant antifibrotic effects on orbital fibroblasts from patients with TAO.
Pharmacokinetics and bioavailability of doxycycline in turkeys.

The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-, 6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two-compartment model. The mean (+/-SD) elimination half-life was 10.6 +/- 0.7, 10.8 +/- 1.5, 7.9 +/- 1.4 and 10.0 +/- 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys, respectively. Mean (+/- SD) total body clearance was 0.19 (+/-0.01), 0.27 (+/-0.03), 0.11 (+/-0.03) and 0.06 (+/-0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old turkeys, respectively. The steady-state volume of distribution was 1.77 (+/-0.2), 2.1 (+/-0.2), 0.7 (+/-0.4) and 0.5 (+/-0.2) L/kg in turkeys of the above mentioned ages, respectively. The AUC value significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day. 3-, 6- and 12-week-old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 micrograms/mL. with tmax values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys the Cmax values were 2.5, 6.1, 4.8 and 3.0 micrograms/mL. with tmax values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 +/- 9.0% (for 12-week-old birds) and 63.5 +/- 7.1% (for 3-week-old birds). The relative bioavailability varied between 40.0 +/- 13.0% (for 12-week-old birds) and 83.7 +/- 14.3% (for 3-week-old birds).
Response of dairy cows in early lactation to additions of cottonseed meal in alfalfa-based diets.

The effect of increasing CP levels by additions of cottonseed meal to diets for early lactation was studied in 24 multiparous Holstein cows. Diets containing 13.8, 17.5, 20.4, and 23.9% CP were fed during three 3-wk periods beginning at wk 4 postpartum. Each cow received three of the four dietary treatments giving 18 observations per treatment in a randomized complete block design. Undegraded intake protein as a fraction of total protein for the diets was . 25, . 32, . 36, and . 39. Dry matter intake increased linearly with increasing dietary CP concentrations. Daily milk yield increased as dietary CP increased from 13.8 to 17.5%. Increased milk yield was accompanied by increased daily yields of milk fat and protein, but the concentration of these components in milk was not altered. The proportion of total milk N that was NPN increased linearly with increasing dietary CP level. Plasma amino acids and urea N were increased by increasing the dietary CP level. The conclusions of the study were that increasing dietary CP levels from 13.8 to 17.5% by the use of cottonseed meal was beneficial to cows consuming alfalfa-based diets in early lactation. Increasing dietary CP above 17.5% showed little benefit in milk yield. Increasing dietary protein caused an increase in blood urea N and milk NPN, indicating N wastage by the animal.
Characterization of Adenosine Receptors Mediating Spinal Sensory Transmission Related to Nociceptive Information in the Rat

Background Adenosine analogs have been shown to produce antinociception after intrathecal administration. To determine the adenosine receptor subtype involved in spinal antinociception, the effects of selective agonists and an antagonist on the evoked potentials recorded from a neonatal rat spinal cord were studied. The measured potentials are a slow ventral root potential (slow VRP), which is the C-fiber-evoked excitatory response associated with nociceptive information; a monosynaptic reflex (MSR), which reflects a non-nociceptive transmission related to motor function; and a dorsal root potential (DRP), which reflects a gamma-aminobutyric acids (GA-BA sub A) receptor-mediated presynaptic inhibition associated with analgesia. Methods The evoked potentials were recorded in response to electric stimulation of a lumbar dorsal root. Dose-response curves of agonists for these responses were obtained to determine their relative potency order. The antagonist dissociation constants (KD values) were estimated by Schild analysis. Results Adenosine agonists dose dependently inhibited the slow VRP and the MSR. However, the slow VRP was five to eight times more sensitive to them than was the MSR. The rank order of agonist potency was N6-cyclohexyladenosine (CHA) = N6-(R)-phenylisopropyladenosine (R-PIA) > 5'-N-ethylcarboxamidoadenosine (NECA) much > CGS 21680 in both responses. 8-Cyclopentyltheophylline produced dose-dependent parallel shifts to the right of NECA dose-response curves for these responses. Schild analysis gave linear plots with slopes near unity. The KD values of CPT for the MSR and the slow VRP were estimated to be 5.5 nM and 4.3 nM, respectively. The DRP was also depressed by adenosine agonists with potency order of CHA > NECA much > CGS 21680. 8-Cyclopentyltheophylline antagonized the inhibitory effects of CHA on the DRP. Conclusions The results indicate that adenosine agonists inhibit spinal sensory transmission related to nociception by acting at the A sub 1 receptors. The A1 receptor also seems to be involved in transmission related to the spinal motor system. Feedback inhibition mediated by GABAA receptors does not contribute to this antinociceptive action.
Tight Bounds for HTN Planning with Task Insertion

Hierarchical Task Network (HTN) planning with Task Insertion (TIHTN planning) is a formalism that hybridizes classical planning with HTN planning by allowing the insertion of operators from outside the method hierarchy. This additional capability has some practical benefits, such as allowing more flexibility for design choices of HTN models: the task hierarchy may be specified only partially, since "missing required tasks" may be inserted during planning rather than prior planning by means of the (predefined) HTN methods. While task insertion in a hierarchical planning setting has already been applied in practice, its theoretical properties have not been studied in detail, yet - only EXPSPACE membership is known so far. We lower that bound proving NEXPTIME-completeness and further prove tight complexity bounds along two axes: whether variables are allowed in method and action schemas, and whether methods must be totally ordered. We also introduce a new planning technique called acyclic progression, which we use to define provably efficient TIHTN planning algorithms.
Ultrasonography for the Evaluation of Visceral Fat and Cardiovascular Risk

Visceral fat accumulation is associated with increased cardiovascular risk. Clinical evaluation of visceral fat is limited because of the lack of reliable and low-cost methods. To assess the correlation between ultrasonography and computed tomography (CT) for the evaluation of visceral fat, 101 obese women, age 50.5±7.7 years with a body mass index of 39.2±5.4 kg/m2, were submitted to ultrasonograph and CT scans. Visceral fat measured by ultrasonography, 1 cm above the umbilical knot, showed a high correlation with CT-determined visceral fat (r =0.67, P <0.0001). The ultrasonograph method showed good reproducibility with an intra-observer variation coefficient of <2%. Both ultrasonograph and CT visceral fat values were correlated with fasting insulin (r =0.29 and r =0.27, P <0.01) and plasma glucose 2 hours after oral glucose load (r =0.22 and r =0.34, P <0.05), indicating that ultrasonography is a useful method to evaluate cardiovascular risk. A significant correlation was also found between visceral fat by CT and serum sodium (r =0.18, P <0.05). A ultrasonograph-determined visceral-to-subcutaneous fat ratio of 2.50 was established as a cutoff value to define patients with abdominal visceral obesity. This value also identified patients with higher levels of plasma glucose, serum insulin and triglycerides and lower levels of HDL-cholesterol, which are metabolic abnormalities characteristic of the metabolic syndrome. Our data demonstrate that ultrasonography is a precise and reliable method for evaluation of visceral fat and identification of patients with adverse metabolic profile.
Development of Bulk Superconducting-Absorber Coupled Transition-Edge Sensor Detectors for Positron Annihilation Spectroscopy

We present a high-resolution bulk tin-absorber coupled transition-edge sensor microcalorimeter to be applied for positron annihilation spectroscopy at 511 keV. We demonstrate an energy resolution of 526 eV at 662 keV from a 137Cs source. This is the best energy resolution reported so far for any available detector at this photon energy. Further works are ongoing to reduce the mechanical vibrations of the cryogenic system in order to optimize the energy resolution of the detector.
Transcriptional and post-translational changes in the brain of mice deficient in cholesterol removal mediated by cytochrome P450 46A1 (CYP46A1)

Cytochrome P450 46A1 (CYP46A1) converts cholesterol to 24-hydroxycholesterol and thereby controls the major pathways of cholesterol removal from the brain. Cyp46a1-/- mice have a reduction in the rate of cholesterol biosynthesis in the brain and significant impairments to memory and learning. To gain insights into the mechanisms underlying Cyp46a1-/- phenotype, we used Cyp46a1-/- mice and quantified their brain sterol levels and the expression of the genes pertinent to cholesterol homeostasis. We also compared the Cyp46a1-/- and wild type brains for protein phosphorylation and ubiquitination. The data obtained enable the following inferences. First, there seems to be a compensatory upregulation in the Cyp46a1-/- brain of the pathways of cholesterol storage and CYP46A1-independent removal. Second, transcriptional regulation of the brain cholesterol biosynthesis via sterol regulatory element binding transcription factors is not significantly activated in the Cyp46a1-/- brain to explain a compensatory decrease in cholesterol biosynthesis. Third, some of the liver X receptor target genes (Abca1) are paradoxically upregulated in the Cyp46a1-/- brain, possibly due to a reduced activation of the small GTPases RAB8, CDC42, and RAC as a result of a reduced phosphorylation of RAB3IP and PAK1. Fourth, the phosphorylation of many other proteins (a total of 146) is altered in the Cyp46a1-/- brain, including microtubule associated and neurofilament proteins (the MAP and NEF families) along with proteins related to synaptic vesicles and synaptic neurotransmission (e.g., SLCs, SHANKs, and BSN). Fifth, the extent of protein ubiquitination is increased in the Cyp46a1-/- brain, and the affected proteins pertain to ubiquitination (UBE2N), cognition (STX1B and ATP1A2), cytoskeleton function (TUBA1A and YWHAZ), and energy production (ATP1A2 and ALDOA). The present study demonstrates the diverse potential effects of CYP46A1 deficiency on brain functions and identifies important proteins that could be affected by this deficiency.
The nucleus of endothelial cell as a sensor of blood flow direction

Summary Hemodynamic shear stresses cause endothelial cells (ECs) to polarize in the plane of the flow. Paradoxically, under strong shear flows, ECs disassemble their primary cilia, common sensors of shear, and thus must use an alternative mechanism of sensing the strength and direction of flow. In our experiments in microfluidic perfusion chambers, confluent ECs developed planar cell polarity at a rate proportional to the shear stress. The location of Golgi apparatus and microtubule organizing center was biased to the upstream side of the nucleus, i.e. the ECs polarized against the flow. These in vitro results agreed with observations in murine blood vessels, where EC polarization against the flow was stronger in high flow arteries than in veins. Once established, flow-induced polarization persisted over long time intervals without external shear. Transient destabilization of acto-myosin cytoskeleton by inhibition of myosin II or depolymerization of actin promoted polarization of EC against the flow, indicating that an intact acto-myosin cytoskeleton resists flow-induced polarization. These results suggested that polarization was induced by mechanical displacement of EC nuclei downstream under the hydrodynamic drag. This hypothesis was confirmed by the observation that acute application of a large hydrodynamic force to ECs resulted in an immediate downstream displacement of nuclei and was sufficient to induce persistent polarization. Taken together, our data indicate that ECs can sense the direction and strength of blood flow through the hydrodynamic drag applied to their nuclei.
Phylogenetic analysis of human metapneumovirus from children with acute respiratory infection in Yamaguchi, Japan, during summer 2009.

Human metapneumovirus (hMPV) belongs to the family Paramyxoviridae, genus Metapneumovirus. It is an important causative agent of acute respiratory infections (ARIs) in humans (1) whose epidemiology in Japan is not known. To better understand the molecular epidemiology of domestic strains of hMPV, we performed phylogenetic analysis of hMPV detected from children with ARIs in Yamaguchi Prefecture during July and August 2009. Table 1 shows patient and virus data. Virus RNA was extracted from throat swabs using a QIAamp Viral RNA Mini Kit (Qiagen, Germantown, Md., USA) and suspended in DNase/RNase-free water. After RNA extraction, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed as previously described (2). Amplicons were purified using a MinElute PCR Purification Kit (Qiagen), and the nucleotide sequences were determined by direct sequencing (2). We performed phylogenetic analysis based on the F gene of hMPV strains using Molecular Evolutionary Genetics Analysis (MEGA) software version 4 (3). Evolutionary distances were estimated using Kimura’s two-parameter method, and a phylogenetic tree was constructed using the neighborjoining method (4). The reliability of the tree was estimated using 1,000 bootstrap replications. The phylogenetic tree revealed that 14 out of the 18 strains detected during the 2009 summer season were clustered in the A2 subgroup, 3 strains were in the B1 subgroup, and 1 strain was in the B2 subgroup (Fig. 1). The 14 strains clustered in subgroup A2 were further classified into 2 subclusters. The nucleotide identities among the strains within the subgroups were 98.4 to 100% for subgroup A2 and 100% for subgroup B1. The nucleotide identities among the strains within the two subclusters of the A2 subgroup were 99.7 and 100%, respectively. In one of the subclusters of the A2 subgroup to which 11 strains belonged, an epidemiological rela-
The integral dose received from a uniformly distributed radioactive isotope.

Methods of calculation of the integral dose received in simple geometrical bodies containing a uniformly distributed γ-ray emitting radioactive isotope are described, and a general relation between this dose and the volume, and the elongation of the body, deduced. These calculations have been extended to the case of a “patient”, composed of cylinders and elliptical cylinders. A table is given, showing the integral dosage-rates in patients of different heights and weights from a uniformly distributed γ-ray emitter. The effect of variation in the quantum energy of the emitted radiation on the integral dose is examined. An expression is found which gives the fraction of the energy due to βparticle emission which is lost from the surface of the patient or animal. This loss may be important in the case of small animals.
Serum NGAL to Clinically Distinguish Cholangiocarcinoma from Benign Biliary Tract Diseases

Aim. To determine whether the serum level of NGAL can discriminate cholangiocarcinoma from benign biliary tract disease in patients. Methods. This study was performed according to a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design. A total of 50 cholangiocarcinoma and 50 benign biliary tract disease cases were randomly selected from a cohort of consecutive cases of biliary tract diseases. Their sera were measured for the levels of NGAL and the widely used serum cholangiocarcinoma marker, carbohydrate antigen 19-9 (CA19-9). Results. The serum CA19-9 and NGAL levels were significantly elevated in cholangiocarcinoma patients (CA19-9: P < .001, NGAL: P < .001). The area under the curve (AUC) of a receiver operating characteristic (ROC) curve analysis for the diagnosis of cholangiocarcinoma of CA19-9 and NGAL was 0.81 and 0.79, respectively. Conclusion. The diagnostic accuracy of serum NGAL and CA19-9 makes them good candidates for use as biomarkers to discriminate cholangiocarcinoma patients from benign biliary tract disease patients.
Magnetic fields in axisymmetric neutron stars

We derive general equations for axisymmetric Newtonian magnetohydrodynamics and use these as the basis of a code for calculating equilibrium configurations of rotating magnetized neutron stars in a stationary state. We investigate the field configurations that result from our formalism, which include purely poloidal, purely toroidal and mixed fields. For the mixed-field formalism, the toroidal component appears to be bounded at less than 7 per cent. We calculate distortions induced both by magnetic fields and by rotation. From our non-linear work, we are able to look at the realm of validity of perturbative work: we find for our results that perturbative-regime formulae for magnetic distortions agree to within 10 per cent of the non-linear results if the ellipticity is less than 0.15 or the average field strength is less than 10^17 G. We also consider how magnetized equilibrium structures vary for different polytropic indices.
Cross Spectral Analysis in Assessment of Baroreflex Gain in Patients with Coronary Artery Disease

Background: Interest in determination of baroreflex sensitivity in clinical practice is growing because of its prognostic information in patients with heart disease. The purpose of the present study was to assess the feasibility of cross spectral analysis in the determination of baroreflex gain from spontaneous RR interval and systolic pressure fluctuations, and to compare the results to the traditional pharmacological method in patients with coronary artery disease.
Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells

The tissue-specific homing of lymphocytes is directed by specialized high endothelial venules (HEV). At least three functionally independent lymphocyte/HEV recognition systems exist, controlling the extravasation of circulating lymphocytes into peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches or appendix), and the synovium of inflamed joints. We report here that antibodies capable of inhibiting human lymphocyte binding to one or more HEV types recognize a common 85- 95-kD lymphocyte surface glycoprotein antigen, defined by the non- blocking monoclonal antibody, Hermes-1. We demonstrate that MEL-14, a monoclonal antibody against putative lymph node "homing receptors" in the mouse, functionally inhibits human lymphocyte binding to lymph node HEV but not to mucosal or synovial HEV, and cross-reacts with the 85-95- kD Hermes-1 antigen. Furthermore, we show that Hermes-3, a novel antibody produced by immunization with Hermes-1 antigen isolated from a mucosal HEV-specific cell line, selectively blocks lymphocyte binding to mucosal HEV. Such tissue specificity of inhibition suggests that MEL- 14 and Hermes-3 block the function of specific lymphocyte recognition elements for lymph node and mucosal HEV, respectively. Recognition of synovial HEV also involves the 85-95-kD Hermes-1 antigen, in that a polyclonal antiserum produced against the isolated antigen blocks all three classes of lymphocyte-HEV interaction. From these studies, it is likely that the Hermes-1-defined 85-95-kD glycoprotein class either comprises a family of related but functionally independent receptors for HEV, or associates both physically and functionally with such receptors. The findings imply that related molecular mechanisms are involved in several functionally independent cell-cell recognition events that direct lymphocyte traffic.
Synthesis and Immobilization of Pt Nanoparticles on Amino-Functionalized Halloysite Nanotubes toward Highly Active Catalysts

A simple and effective method for the preparation of platinum nanoparticles (Pt NPs) grown on amino-functionalized halloysite nanotubes (HNTs) was developed. The nanostructures were synthesized through the functionalization of the HNTs, followed by an in situ approach to generate Pt NPs with diameter of approximately 1.5 nm within the entire HNTs. The synthesis process, composition and morphology of the nanostructures were characterized. The results suggest PtNPs/NH2-HNTs nanostructures with ultrafine PtNPs were successfully synthesized by green chemically-reducing H2PtCl6 without the use of surfactant. The nanostructures exhibit promising catalytic properties for reducing potassium hexacyanoferrate(III) to potassium hexacyanoferrate(II). The presented experiment for novel PtNPs/NH2-HNTs nanostructures is quite simple and environmentally benign, permitting it as a potential application in the future field of catalysts.