Miracle-dz/UniFAR-FTUs huggingface dataset:
Metamizol, a non‐opioid analgesic, acts via endocannabinoids in the PAG‐RVM axis during inflammation in rats

The most commonly used drugs against pain act by inhibiting the cyclooxygenases (COXs). Metamizol (dipyrone) inhibits the COXs and is widely used in Europe and Latin America as a non‐opioid analgesic. One target of metamizol and other non‐opioid analgesics is the periaqueductal grey matter (PAG), where they trigger descending inhibition of spinal nociceptive transmission. Also, cannabinoids exert an analgesic action at several structures in the peripheral and central nervous system, including the PAG. The present study investigates whether the antinociceptive action of metamizol in the lateral‐ventrolateral (LVL) PAG during inflammation is related to endocannabinoids. In anaesthetized rats, unitary action potentials were recorded from spinal nociceptive neurons with receptive fields in the ipsilateral hind paw. Inflammation of the paw induced neuronal hyperexcitability, which was attenuated by intra‐LVL‐PAG microinjection of metamizol either at the beginning of inflammation or when hyperexcitability was fully established. In both cases, the antinociceptive effect of metamizol was reduced by a microinjection of AM251, an antagonist at the CB1 cannabinoid receptor, either into the LVL‐PAG or into the rostral ventromedial medulla (RVM). The RVM is a downstream structure that funnels PAG‐derived descending inhibition into the spinal cord. These results show that endocannabinoids and their CB1 receptor (1) contribute at the LVL‐PAG to the antinociceptive effects of metamizol, and possibly other non‐opioid analgesics; and (2) participate in the PAG‐derived activation of RVM descending antinociceptive influences.
Determination of Chlorfenvinphos in Soils by Microwave‐Assisted Extraction and Stripping Voltammetry with an Ultramicroelectrode

Abstract A methodology for the determination of the pesticide chlorfenvinphos by microwave‐assisted solvent extraction and square‐wave cathodic stripping voltammetry at a mercury film ultramicroelectrode in soil samples is proposed. Optimization of microwave solvent extraction performed with two soils, selected for having significantly different properties, indicated that the optimum solvent for extracting chlorfenvinphos is hexane‐acetone (1∶1, v/v). The voltammetric procedure is based on controlled adsorptive accumulation of the insecticide at the potential of−0.60 V (vs. Ag/AgCl) in the presence of Britton‐Robinson buffer (pH 6.2). The detection limit obtained for a 10 s collection time was 3.0×10−8 mol l−1. The validity of the developed methodology was assessed by recovery experiments at the 0.100 µg g−1 level. The average recoveries and standard deviations for the global procedure reached by MASE‐square‐wave voltammetry were 90.2±2.8% and 92.1±3.4% for type I (soil rich in organic matter) and type II (sandy soil) samples, respectively. These results are in accordance to the expected values which show that the method has a good accuracy.
Factors Associated with the Utilization of Institutional Delivery Service among Mothers.

BACKGROUND Assessment of utilization of institutional delivery services is crucial to reduce risk of maternal mortality and morbidity in countries like Nepal. This study was conducted to find out the proportion of utilization of institutional delivery service and associated factors among mothers. METHODS Data was collected from the total of 129 mothers of Kathar VDC, Chitwan district who delivered baby within last one year proceeding the period of data collection using census method. Descriptive statistics and binary logistic regression analysis were applied. RESULTS Out of 129 mothers, 78.3% had their delivery in the health facilities. Binary logistic analysis showed number of factors associated with utilization of institutional delivery service such as ethnicity, respondents educational level, number of pregnancy, number of ANC visit and birth preparedness status. But in the multivariable logistic regression analysis, no. of ANC visit (AOR = 10.03, 95 % CI = 1.02-98.29) was only independent factors affecting institutional delivery service utilization. CONCLUSIONS A number of factors have been shown to affect the utilization of institutional delivery. Therefore, concerned authority should plan and implement awareness programme aiming at increasing antenatal clinic visits and utilization of institutional delivery service.
A Model for Setting Analytical Quality Specifications and Design of Control for Measurements on the Ordinal Scale

Abstract A model for characterization of measurements on the ordinal scale is presented. It is based on transformation of the calculated fractions (fractiles) of positives from measurements on samples with known concentrations to a probit-natural log (probit-ln) scale. Such measurements could be made by other methods on ratio or difference scales but, for convenience (for example for speed or low cost), are measured on the ordinal scale by “simple” methods. The model is examined, and verified, using three examples from published data (haemoglobin, glucose, and leukocytes) and an external quality assessment survey on measurements of streptococcus. We show that it is possible to obtain reliable analytical quality specifications and to establish design of control systems for measurements on the ordinal scale. It is concluded that the presented probit-ln model for the ordinal scale is a tool which can improve and facilitate (i) characterizing methods with measurements on the ordinal scale, (ii) defining analytical quality specifications, (iii) designing external assessment as well as internal control schemes, (iv) validation of methods with measurements on the ordinal scale according to the analytical quality specifications, and further, (v) reduction of the number of samples required for method validation and the number of replicate measurements needed.
Epinephrine and Nor-Epinephrine Effects on Social Dominance Behavior

Effects of epinephrine and nor-epinephrine on social dominance behavior in 24 male C57BL/6J mice were investigated. The social dominance hierarchy was created by placing pairs of Ss in a linear maze. The only way S could get to the goal box was by pushing the opposing S out. The dominant S pushed the submissive S out of the maze. After the dominance hierarchy was established, each S was placed in the dominance situation under each of the drug conditions, epinephrine and nor-epinephrine. The results showed that all conditions were significantly different from each other, with the greatest amount of dominance behavior being shown under nor-epinephrine and the greatest submissive behavior under epinephrine. It was concluded that epinephrine and nor-epinephrine may have differential effects on social dominance behavior.
Analysis of the RNA recognition motifs of human neuronal ELAV-like proteins in binding to a cytokine mRNA.

Human neuronal Elav-like proteins contain three RNP-type RNA recognition motifs (RRMs). Previous reports demonstrated that a single RRM of the proteins is not sufficient to bind to the uridine-rich stretch in the 3' untranslated region of mRNAs and that the bi-RRM peptide consisting of the first two RRMs is necessary for the binding. The present study was designed to examine the potential contributions of the first two RRMs when binding to a cytokine mRNA. Deletions of the internal or terminal amino acid residues of the first RRM (RRM1) of the HuC/ple21 ELAV-like protein completely abolished RNA binding. However, removal of any region of the second RRM (RRM2) except for the eight amino acid residues, which correspond to the potent fourth beta-sheet structure of RRM2, did not affect RNA binding. Conjugation of the eight amino acid residues to RRM1 enhanced the RNA binding as well as the entire RRM2, indicating that the octapeptide of RRM2 can be compensated for by the binding function of RRM2. The present study also showed that the substitutions of glutamic acid at 42 for aspartic acid and leucine at 44 for phenylalanine in the first potent alpha-helix structure of RRM1, as were seen in another ELAV-like protein Hel-N1, markedly affected the RNA binding.
Expansion of CD34+ Cells on Telomerized Human Stromal Cells without Losing Erythroid-Differentiation Potential in a Serum-Free Condition

Erythropoiesis progresses from stem cell expansion on stromal cells through the formation of an erythroblastic island. Our aim was to assess the feasibility of using human stromal cells for erythroid production and differentiation. When cord blood CD34+ cells were cocultured with telomerized human stromal cells (hTERT-stromal cells) for 2 weeks, the CD34+ cells and burst-forming units-erythroid (BFU-E) significantly expanded, and a few hematopoietic cells transmigrated below the stromal layer. When nonadherent hematopoietic progenitor cells that had expanded above the hTERT-stromal cells (group B) were collected and subjected to our erythroid-differentiation protocol, they differentiated into erythroblasts with a slight hemoglobin synthesis. When the few hematopoietic cells that had transmigrated below the stromal layer were expanded for an additional 2 to 6 weeks, they exhibited a cobblestone-like appearance, and a large amount of BFU-E clambered weekly from the underside of the stromal layer to above the stromal layer (group C). When the hematopoietic progenitor cells in group C were subjected to the erythroid-differentiation protocol, large numbers of mature erythroblasts (more than 300,000 times the initial CD34+ cell number) were produced. Our hTERT-stromal expansion protocol may contribute to the construction of a system for large-scale, long-term production of erythroid cells.
Rapamycin impairs UV induction of mutant‐p53 overexpressing cell clusters without affecting tumor onset

Because of its antitumor effect, the immunosuppressant rapamycin holds great promise for organ transplant recipients in that it may lower their cancer risk. In a mouse model, we showed previously that rapamycin inhibits the outgrowth of primary skin carcinomas induced by UV radiation. However, the tumors that did grow out showed an altered p53 mutation spectrum. Here, we investigated whether this shift in p53 mutations already occurred in the smallest tumors, which were not affected in onset. We found that rapamycin did not alter the mutational spectrum in small tumors and in preceding microscopic clusters of cells expressing mutant‐p53. However, rapamycin did reduce the number of these cell clusters. As this reduction did not affect tumor onset, we subsequently investigated whether rapamycin merely suppressed expression of mutated p53. This was not the case, as we could demonstrate that switching from a diet with rapamycin to one without, or vice versa, did not affect the number of existing mutant‐p53 expressing cell clusters. Hence, rapamycin actually reduced the formation of mutant‐p53 cell clusters. In wild‐type and p53‐mutant mice, we could not measure a significant enhancement of UV‐induced apoptosis, but we did observe clear enhancement in human skin equivalents. This was associated with a clear suppression of HIF1α accumulation. Thus, we conclude that rapamycin reduces the formation of mutant‐p53‐expressing cell clusters without affecting tumor onset, suggesting that tumors grow out of a minor subset of cell clusters, the formation of which is not affected by rapamycin.
Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas.

BACKGROUND & AIMS It has recently been suggested that infiltrating adenocarcinoma of the pancreas arises from histologically well-defined precursor ductal lesions called pancreatic intraepithelial neoplasia (PanIN-1A, -1B, -2, and -3). This study examined alterations in the pattern and the level of expression of several mucin genes (MUC1, MUC2, MUC5AC, and MUC6) and mucin-associated tumor antigens (Nd2 and sialyl Tn) in these precursor lesions. METHODS We examined 139 PanINs and 68 infiltrating ductal adenocarcinomas of the pancreas by using immunohistochemistry and in situ hybridization methods. RESULTS Overexpression of MUC1, a pan-epithelial mucin, and MUC6, a pyloric-gland mucin, and de novo expression of MUC5AC, a gastric foveolar mucin, was observed in all stages of PanINs and invasive ductal adenocarcinoma. In contrast, the expression of mucin-associated carbohydrate antigen, sialyl Tn, was markedly increased only in PanlN-3 and invasive ductal adenocarcinoma. In addition, a decrease in the expression of these mucin-associated peptide and carbohydrate antigens was correlated with the degree of differentiation of the tumor. CONCLUSIONS Expression of both gastric-foveolar and pyloric-gland mucin in PanINs is an early event, whereas sialyl Tn expression is a late event in the recently defined progression model of pancreatic carcinogenesis. This altered mucin gene expression provides new insight into the role of cell lineage-associated metaplasia in pancreatic carcinogenesis.
A 1-year multicenter randomized double-blind comparison of repaglinide and glyburide for the treatment of type 2 diabetes. Dutch and German Repaglinide Study Group.

OBJECTIVE Repaglinide is a newly developed oral blood glucose-lowering agent that exerts its effect by stimulating insulin secretion. This multicenter study was designed to compare the efficacy and safety of this drug with glyburide in a 1-year randomized double-blind study of outpatients with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 424 subjects (154 women, 270 men) participated and had the following characteristics: age, 61 +/- 9 years; duration of diabetes. 8 years (range 0.5-35); BMI, 28.3 +/- 3.5 kg/m2; HbA1c, 7.1 +/- 1.4%; and fasting plasma glucose, 10.8 +/- 3.1 mmol/l. The majority of the subjects (91%) were previously treated with sulfonylurea, alone or in combination with metformin. The patients were randomized to a 2:1 ratio of repaglinide (0.5-4 mg t.i.d.) or glyburide (1.75-10.5 mg daily) treatment. The study protocol included a screening visit to assess patient eligibility; a titration period of 6-8 weeks, during which the dosages of repaglinide and glyburide were optimized; and a subsequent 12-month treatment period on fixed, optimal dosages. RESULTS The trial was completed by 320 subjects, 211 (74%) in the repaglinide and 109 (78%) in the glyburide group. HbA1c initially decreased in both groups and then increased during the second half-year of the maintenance period to a similar extent in the repaglinide and glyburide subjects (0.58 and 0.45% vs. at screening, respectively). In the small group of subjects who previously controlled their condition with diet only (n = 37), a sustained improvement of metabolic control could be observed with both drugs, which was slightly better with glyburide than with repaglinide (theta HbA1c -2.4 vs. -1.0%; P < 0.05). The same trends were seen with fasting plasma glucose. There were no changes in serum lipids. Over the course of the study, 15% of the repaglinide-treated and 13% of glyburide-treated subjects withdrew due to adverse events, mostly hyperglycemia. No differences in adverse events between both drugs were reported. There were no differences in incidences of hypoglycemia. CONCLUSIONS Repaglinide is a safe and efficacious oral blood glucose-lowering agent, with a potency similar to that of glyburide. Its rapid onset of action and hepatic clearance allows meal-related administration, including in subjects with impaired kidney function.
Functionalized silk-based biomaterials for bone formation.

Silks are being reassessed as biomaterial scaffolds due to their unique mechanical properties, opportunities for genetic tailoring of structure and thus function, and recent studies clarifying biocompatibility. We report on the covalent decoration of silk films with integrin recognition sequences (RGD) as well as parathyroid hormone (PTH, 1-34 amino acids) and a modified PTH 1-34 (mPTH) involved in the induction of bone formation. Osteoblast-like cell (Saos-2) responses to the decorated silk films indicate that the proteins serve as suitable bone-inducing matrices. Osteoblast-like cell adhesion was significantly increased on RGD and PTH compared to plastic, mPTH, and the control peptide RAD. At 2 weeks of culture, message levels of alkaline phosphatase were similar on all substrates, but by 4 weeks, alkaline phosphatase mRNA was greatest on RGD. At 2 weeks of culture, alpha 1(I) procollagen mRNA was elevated on silk, RGD, RAD, and PTH, and hardly detectable on mPTH and plastic. However, by 4 weeks RGD demonstrated the highest level compared to the other substrates. Osteocalcin message levels detected by RT-PCR were greatest on RGD at both time points. Calcification was also significantly elevated on RGD compared to the other substrates with an increase in number and size of the mineralized nodules in culture. Thus, RGD covalently decorated silk appears to stimulate osteoblast-based mineralization in vitro.
Low-spur technique for Integer-N phase-locked loop

In this paper, we presents a low-spur phase locked loop (PLL) system for wireless applications. The low-spur frequency synthesizer randomizes the periodic ripples on the control voltage of the voltage-controlled oscillator (VCO) in order to reduce the reference spur at the output of the PLL. A new random clock generator is presented to perform a random selection of phase frequency detector (PFD) control for charge pump at locked state. The proposed frequency synthesizer was fabricated in TSMC 0.18-μm CMOS process. The PLL has achieved the phase noise of -105 dBc/Hz at 1MHz offset frequency and reference spurs below -72dBc.
Characteristics and Spatial Variability of Saline-Alkaline Soil Degradation in the Typical Yellow River Delta Area of Kenli County, China

As an important area of reserve land resources, the Yellow River Delta is faced with the problem of soil salinization. Grasping the characteristics of soil salinity as well as its spatial variation patterns is an important foundation of prevention, control and utilization of saline soil. This study selected Kenli County of the Yellow River Delta, obtained soil salinity data through field survey and lab experiment, and used statistical, GIS interpolation and buffer analysis methods to analyze the characteristics of soil salinity and its spatial variation patterns. Our results showed that the general soil salinity in the study area was mainly moderate and there was a significant positive correlation between different soil layers of 0 - 15 cm, 15 - 30 cm and 30 - 45 cm and soil salinity increased with the increase of soil depth. The areas with high soil salinity in each soil layer mainly distributed in the east near the Bo Sea in the county, while the areas with lower soil salinity mainly distributed in the southwest, centre and the two sides of the Yellow River in the northeast. Soil salinity showed a trend of decrease with the increase in distance to the Bo Sea, while stretching from the Yellow River, it showed increase tendency with the increase in distance to the Yellow River. The order from high soil salinity to low of different vegetation types was naked land → suaeda glauca → tamarix → vervain → reed → couch grass → paddy → cotton → winter wheat → maize; the order for different geomorphic types was depression → slightly sloping ground → slow hillock → high flood land. This study preliminary delineated the characteristics of soil salinity as well as its spatial variation patterns in the study area, and provided scientific basis for soil resource sustainable utilization in the Yellow River Delta.
AMIGO is expressed in multiple brain cell types and may regulate dendritic growth and neuronal survival

Amphoterin‐induced gene and ORF (AMIGO) is a brain‐enriched transmembrane immunoglobulin (Ig) superfamily protein with six extracellular leucine‐rich repeats (LRR) and a single immunoglobulin‐like (Ig) domain. We report here that AMIGO is a glycosylated protein widely expressed in the central nervous system (CNS), and can be found in neurons, astrocytes as well as oligodendrocytes. In morphologically mature primary neurons, endogenous AMIGO, and transfected full length AMIGO (AMIGO‐FL) are largely dendritic, while AMIGO with its LRR domain deleted (AMIGO‐Ig) is predominantly axonal. In line with AMIGO's dendritic localization, siRNA‐mediated silencing of AMIGO resulted in reduced dendritic growth of cortical neurons in culture. SH‐SY5Y cells stably over‐expressing AMIGO are more resistant to apoptosis induced by staurosporine and H2O2 compared to vector controls. AMIGO therefore likely plays important roles in dendritic outgrowth during development, and could modulate the survival of developing and adult neurons. J. Cell. Physiol. 227: 2217–2229, 2012. © 2011 Wiley Periodicals, Inc.
Microsatellite alterations suggestive of organ‐specific asthma and atopy in exhaled breath condensate

Several genetic linkage studies demonstrated the existence of organ-specific disease susceptibility genes which may induce asthma and atopy (1). In particular, chromosomes 6p and 14q seem to host asthma/atopy susceptibility genes (2). Microsatellite alterations (MAs) in these regions were detected in sputum cells of asthmatics (3). The MAs can serve as a valid tool to discriminate between asthma and COPD patients (4). MAs are undetectable in nasal cytology samples from patients with allergic rhinitis as bronchial asthma MAs are specific for disease target organ (5). The possibility to analyze MAs in exhaled breath condensate (EBC) was demonstrated. The method was validated by the comparative study of the EBC DNA MAs and paired lung tissue DNA, allowing the use of this sample in lung disease genetic studies (6). The aim of the study was to investigate MAs of chromosomes 6p and 14q in EBC DNA of a group of asthmatics with atopy (AAs), a group of nonatopic asthmatics (ANAs) and a group of nonasthmatic atopics (As), and to verify whether atopy and asthma have different genetic traits. Twenty-eight consecutive AAs, 13 ANAs, 15 As and 15 healthy subjects (HS) were enrolled (Table 1). The diagnosis of asthma and the assessment of its severity were performed according to GINA. Peripheral whole blood (WB) and EBC were collected from each patient. DNA from WB and EBC was extracted by using QIAmp DNA mini Kit (Qiagen, Mican, Italy). Five fluorescence labeled markers located at chromosomes 14q (D14S258, D14S588, D14S292) and 6p (D6S2223, D6S263) were used to evaluate LOH and MI. DNA was amplified by the PCR. The samples were analyzed by capillary electrophoresis on ABI PRISM 310 (Applied Biosystems, Monza, Italy). Good quality DNA in terms of integrity and amount (mean quantity: 20 ng/ ll) was obtained from all EBC samples. None of the HS exhibited genetic alteration of the five markers tested supporting Paraskakis’ hypothesis that these markers are disease-specific (4). MAs in WB-DNA were absent. The microsatellites D14S292 and D6S2223 drive the susceptibility to atopy and asthma, respectively, other microsatellites are involved in both phenotypes. The increased number of MAs is associated with a declined lung function, severe asthma and high degree of atopy. The AAs exhibited the highest percentages of MAs at 6p and 14q. The highest number of MAs was found in the EBC DNA of AAs confirming the results obtained from sputum DNA (4). In accordance with Parashakis et al. (4) the correlation Exhaled microsatellite alterations at chromosomes 6p and 14q are suggestive of organ-specific asthma and atopy. ALLERGY Net