Miracle-dz/UniFAR-FTUs huggingface dataset:
Nociceptin‐induced apparent hyperalgesia in mice as a result of the prevention of opioid autoanalgesic mechanisms triggered by the stress of an intracerebroventricular injection

Summary— The effects on nociperception of nociceptin/Orphanin FQ (noc/OFQ), the endogenous ligand of the ORL1 (opioid receptor like 1) receptor, have been evaluated in mice upon intracerebroventricular injection of 10 to 10 000 ng doses of the peptide. In the hot plate test (55 °C) the licking, rearing and jump latencies were significantly reduced by noc/OFQ (100–250 ng). Noc/OFQ (100–1000 ng) also reduced the latency to tail withdrawal in the tail flick test. In the formalin test (injection in a hind paw of a formalin solution), noc/OFQ (100 ng) increased significantly the duration of paw licking and/or biting at the earliest period of observation. In the writhing test, the number of writhes evoked by intraperitoneal administration of dilute acetic acid was not modified by noc/OFQ at doses in the range of 10–1000 ng, but was decreased by 10 000 ng. The reduction in jump latency in the hot plate test was observed even when mice were pretreated with morphine (2 mg/kg, sc). The analgesic effect of acetorphan (5 mg/kg, iv) was also reduced by nociceptin (100 ng); on the other hand the hyperalgesic effect of naloxone (4.5 mg/kg, sc) was not additive with that of nociceptin (100 ng). Comparing in various tests the nociceptive thresholds of uninjected mice to that of saline icv injected mice, it appeared that the latter injection induced an increase in these thresholds which was prevented by nociceptin. It is suggested that nociceptin displays hyperalgesic effects by preventing autoanalgesic (opioidergic) mechanisms triggered by the stress elicited by intracerebroventricular injection.
The proteolytic system of Lactobacillus sanfrancisco CB1: purification and characterization of a proteinase, a dipeptidase, and an aminopeptidase

A cell envelope 57-kDa proteinase, a cytoplasmic 65-kDa dipeptidase, and a 75-kDa aminopeptidase were purified from Lactobacillus sanfrancisco CB1 sourdough lactic acid bacterium by sequential fast protein liquid chromatography steps. All of the enzymes are monomers. The proteinase was most active at pH 7.0 and 40 degrees C, while aminopeptidase and dipeptidase had optima at pH 7.5 and 30 to 35 degrees C. Relatively high activities were observed at the pH and temperature of the sourdough fermentation. The proteinase is a serine enzyme. Urea-polyacrylamide gel electrophoresis of digest of alpha s1- and beta-caseins showed differences in the pattern of peptides released by the purified proteinase and those produced by crude preparations of the cell envelope proteinases of Lactobacillus delbrueckii subsp. bulgaricus B397 and Lactococcus lactis subsp. lactis SK11. Reversed-phase fast protein liquid chromatography of gliadin digests showed a more-complex peptide pattern produced by the proteinase of Lactobacillus sanfrancisco CB1. The dipeptidase is a metalloenzyme with high affinity for dipeptides containing hydrophobic amino acids but had no activity on tripeptides or larger peptides. The aminopeptidase was also inhibited by metal-chelating agents, and showed a broad N-terminal hydrolytic activity including di- and tripeptides. Km values of 0.70 and 0.44 mM were determined for the dipeptidase on Leu-Leu and the aminopeptidase on Leu-p-nitroanilide, respectively.
Cell domain‐dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region

An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3–5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7–10 days post pilocarpine), via cell domain‐dependent alterations in synaptic current properties, concomitant with the occurrence of interictal‐like activity in vivo. During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal‐like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity.
High Performance Ge pMOSFETs With HfO2/Hf-Cap/GeOx Gate Stack and Suitable Post Metal Annealing Treatments

An equivalent oxide thickness of ~0.53 nm, gate leakage current density of <inline-formula> <tex-math notation="LaTeX">$\sim 10^{-4}\text{A}$ </tex-math></inline-formula>/cm<sup>2</sup> at <italic>V</italic> <sub>FB</sub> + 1 V, <italic>I</italic><sub>ON</sub>/ <italic>I</italic><sub>OFF</sub> ratio of <inline-formula> <tex-math notation="LaTeX">$10^{\text {4}}$ </tex-math></inline-formula>, subthreshold swing of 136 mV/dec, and peak hole mobility of 375 cm<sup>2</sup>/V-s at <italic>N</italic> <inline-formula> <tex-math notation="LaTeX">$_{\text {inv}} = 1.6 \times 10^{12}$ </tex-math></inline-formula> cm<sup>−2</sup> in Ge p-type metal–oxide–semiconductor-field-effect transistors (pMOSFETs) are achieved by HfO<sub>2</sub>/Hf-cap/GeO<sub>x</sub> gate stack with suitable post-metal-annealing (PMA) treatments. Such a high mobility in Ge pMOSFETs can be attributed to an ultrathin GeO<sub>x</sub> layer at the surface of Ge substrate. Ge<sup>+</sup> and Ge<sup>+2</sup> in GeO<sub>x</sub> layer are re-oxidized to higher oxidation state by gettered oxygen, which is captured by Hf-cap from GeO<sub>x</sub> and HfO<sub>2</sub> during PMA. The minimized contents of Ge<sup>+1</sup> and Ge<sup>+2</sup> in GeO<sub>x</sub> are crucial to achieve excellent electrical characteristics.
Immune responses of thymusf/ymphocyte embryonic chimeras: studies on tolerance and major histocompatibility complex restriction in Xenopus

A new model has been developed to address the question of whether T cells that traverse an allogeneic thymus during early and late life become restricted to interact, in vivo, with other leukocytes and target cells that display the major histocompatibility complex (MHC) antigens of the thymus haplotype. Chimeras were made microsur‐ gically with pairs of 24‐h‐old Xenopus embryos such that the anterior region of an embryonic chimera contained the thymus anlagen and was of one MHC genotype, whereas the posterior region contained the anlagen of all hemopoietic cells and was of another genotype. Assays to determine the MHC haplotype restriction specificity of T cells in chimeras that had been reared through metamorphosis involved: specific antibody responses (IgM and IgG) to dinitrophenylated keyhole limpet hemocyanin; rejection of minor H locus disparate skin grafts that expressed the MHC antigens of either the thymus donor or the lymphocyte donor; and mixed leukocyte culture. MHC‐mismatched chimeras displayed split tolerance since they accepted skin grafts of the thymus haplotype but had lymphocytes that proliferated in response to MHC antigens of the thymus donor strain as well as to MHC antigens of third‐party donors. IgM responses of MHC‐matched and MHC‐mismatched chimeras and of nonchimeric controls did not differ. However, the IgG responses of MHC‐mismatched thymus/ lymphocyte chimeras peaked later than those of MHC‐matched chimeras and normal controls. Data from skin grafting protocols were consistent with the proposition that there may be in vivo selection of T cells reactive to minor H antigens presented in association with the MHC antigens of the thymus rather than the MHC antigens of the lymphocytes themselves. These data suggest that although it is not absolute, there is thymic selection of the T cell repertoire in Xenopus.
A new method for the capture of surface proteins in Plasmodium falciparum parasitized erythrocyte.

INTRODUCTION We propose a new method for the selective labeling, isolation and electrophoretic analysis of the Plasmodium falciparum protein exposed on the erythrocyte cell surface. Historically, membrane surface proteins have been isolated using a surface biotinylation followed by capture of biotin-conjugated protein via an avidin/streptavidin-coated solid support. The major drawback of the standard methods has been the labeling of internal proteins due to fast internalization of biotin. METHODOLOGY To solve this problem, we used a biotin label that does not permeate through the membrane. As a further precaution to avoid the purification of non surface exposed proteins, we directly challenged whole labeled cells with avidin coated beads and then solubilized them using non ionic detergents. RESULTS A marked enrichment of most of the RBC membrane proteins known to face the external surface of the membrane validated the specificity of the method; furthermore, only small amounts of haemoglobin and cytoskeletal proteins were detected. A wide range of P. falciparum proteins were additionally described to be exposed on the erythrocyte surface. Some of them have been previously observed and used as vaccine candidates while a number of newly described antigens have been presently identified. Those antigens require further characterization and validation with additional methods. CONCLUSION Surface proteins preparations were very reproducible and identification of proteins by mass spectrometry has been demonstrated to be feasible and effective.
Breaking up and making up: The secret life of the vacuolar H+‐ATPase

The vacuolar ATPase (V‐ATPase; V1Vo‐ATPase) is a large multisubunit proton pump found in the endomembrane system of all eukaryotic cells where it acidifies the lumen of subcellular organelles including lysosomes, endosomes, the Golgi apparatus, and clathrin‐coated vesicles. V‐ATPase function is essential for pH and ion homeostasis, protein trafficking, endocytosis, mechanistic target of rapamycin (mTOR), and Notch signaling, as well as hormone secretion and neurotransmitter release. V‐ATPase can also be found in the plasma membrane of polarized animal cells where its proton pumping function is involved in bone remodeling, urine acidification, and sperm maturation. Aberrant (hypo or hyper) activity has been associated with numerous human diseases and the V‐ATPase has therefore been recognized as a potential drug target. Recent progress with moderate to high‐resolution structure determination by cryo electron microscopy and X‐ray crystallography together with sophisticated single‐molecule and biochemical experiments have provided a detailed picture of the structure and unique mode of regulation of the V‐ATPase. This review summarizes the recent advances, focusing on the structural and biophysical aspects of the field.
SURFACE: a database of protein surface regions for functional annotation

The SURFACE (SUrface Residues and Functions Annotated, Compared and Evaluated, URL http://cbm.bio.uniroma2.it/surface/) database is a repository of annotated and compared protein surface regions. SURFACE contains the results of a large-scale protein annotation and local structural comparison project. A non-redundant set of protein chains is used to build a database of protein surface patches, defined as putative surface functional sites. Each patch is annotated with sequence and structure-derived information about function or interaction abilities. A new procedure for structure comparison is used to perform an all-versus-all patches comparison. Selection of the results obtained with stringent parameters offers a similarity score that can be used to associate different patches and allows reliable annotation by similarity. Annotation exerted through the comparison of regions of protein surface allows the highlighting of similarities that cannot be recognized by other methods of sequence or structure comparison. A graphic representation of the surface patches, functional annotations and the structural superpositions is available through the web interface.
Sliding mode-based multi-loop current control of a LCL grid-tied converter

This paper presents a current control method for LCL grid-tied converters using sliding mode algorithm in a multi-loop framework. The inner loop is implemented through a sliding mode approach to obtain fast and robustness convergence. The capacitor voltage is controlled in the inner control loop making this variable to behave like a controlled voltage source. The reference for the inner control loop is given by the outer loop. The outer loop can then be simply designed as simple L grid-tied converter. Simulation results demonstrate the performance of the proposed control strategy and show good tracking capability of the proposed scheme. Moreover, Hardware in the Loop simulation results are obtained in order to evaluate the performance of the proposed control law running on Digital Signal Processor.
The Lifestyle Interventions and Independence for Elders Study: Design and Methods

Background. As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking. A Phase 3 randomized controlled trial is needed to fill this evidence gap. Methods. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled trial designed to compare a supervised moderate-intensity physical activity program with a successful aging health education program in 1,600 sedentary older persons followed for an average of 2.7 years. Results. LIFE's primary outcome is major mobility disability, defined as the inability to walk 400 m. Secondary outcomes include cognitive function, serious fall injuries, persistent mobility disability, the combined outcome of major mobility disability or death, disability in activities of daily living, and cost-effectiveness. Conclusions. Results of this study are expected to have important public health implications for the large and growing population of older sedentary men and women.
The first Meckel oration: on the causes of morphological differences in a population of guinea pigs.

The first morphological abnormality considered here was of a very superficial sort: deviations from the smooth coat of wild cavies and most guinea pigs. The deviations of "rough-furred" individuals range from a single irregularity or a single pair of rosettes to the "full rough" pattern. Roughness may be restricted to the hind toes, forehead, or hair around the eyes or belly, or (very rarely) to a small area on one side of the back. There is no indication of gene control in the last, and no analysis of the only strain (in Professor Castle's laboratory) that I have seen, of roughness restricted to the belly. A dominant gene, R, in combination with a semidominant modifier, M, account for the fancier roughs (R-MM toes only, R-mm full rough). A gene, st, that is completely dominant in the absence of R, semidominant in its presence, was descended from 3 animals from outside the colony. It accounts for a large forehead rosette, usually with a small white spot in front of its center. A statistically semidominant gene, Re, with extremely irregular, often asymmetric penetrance tends to cause rosettes about the eyes. This arose by mutation late in the history of the Whitman colony. It is strengthened by presence of R MM. Considerable variation occurs in the numbers of dorsal rosettes of R Mm and R mm. These have not been analyzed satisfactorily because the genetic differences are confounded by nongenetic ones. It is not practicable to summarize briefly all of the complex interaction effects of these factors, but it may be noted that the most surprising one had to do with genes St and R. The forehead rosette due to rr St closely resembles that of R mm (except for the absence of the pleiotropic white spot). The combination, R mm St St, shows none of the expected enhancement but instead shows nearly complete cancellation of the rosette. Moreover, the anterior dorsal rosettes of R mm st st are much reduced and seemingly shoved backward and laterally to give a large smooth shield back of the ears. St St also reduces the usual dorsal pair of rosettes of R Mm. With St st, all of these antagonistic effects are weaker and less regular. Another morphological deviation to be considered was the fairly common restoration of an atavistic little toe. (ABSTRACT TRUNCATED AT 400 WORDS)
Manipulation of Strawberry Fruit Softening by Antisense Expression of a Pectate Lyase Gene1

Strawberry (Fragaria ×ananassa, Duch., cv Chandler) is a soft fruit with a short postharvest life, mainly due to a rapid lost of firm texture. To control the strawberry fruit softening, we obtained transgenic plants that incorporate an antisense sequence of a strawberry pectate lyase gene under the control of the 35S promoter. Forty-one independent transgenic lines (Apel lines) were obtained, propagated in the greenhouse for agronomical analysis, and compared with control plants, non-transformed plants, and transgenic lines transformed with the pGUSINT plasmid. Total yield was significantly reduced in 33 of the 41 Apel lines. At the stage of full ripen, no differences in color, size, shape, and weight were observed between Apel and control fruit. However, in most of the Apel lines, ripened fruits were significantly firmer than controls. Six Apel lines were selected for further analysis. In all these lines, the pectate lyase gene expression in ripened fruit was 30% lower than in control, being totally suppressed in three of them. Cell wall material isolated from ripened Apel fruit showed a lower degree of in vitro swelling and a lower amount of ionically bound pectins than control fruit. An analysis of firmness at three different stages of fruit development (green, white, and red) showed that the highest reduction of softening in Apel fruit occurred during the transition from the white to the red stage. The postharvest softening of Apel fruit was also diminished. Our results indicate that pectate lyase gene is an excellent candidate for biotechnological improvement of fruit softening in strawberry.
Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma

DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells.
Illustration of flywheel energy storage system performance for engineering technology students

Experiments were conducted to illustrate the performance of a flywheel energy storage system (FESS) for electrical engineering technology students. The flywheel was coupled to a permanent magnet synchronous machine (PMSM), which can motor to accelerate the flywheel, and which can regenerate electrical power by extracting energy from the flywheel. The PMSM was connected to a battery bank and DC motors via a bi-directional power converter. The power converter can motor the PMSM by inverting DC power drawn from batteries, and can rectify AC power generated by the PMSM. This system was used to effectively illustrate how energy can be stored in a FESS, and how a FESS can provide power to electrical loads during short duration power source failures.
Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group.

PURPOSE To compare the efficacy and tolerability of anastrozole (1 and 10 mg once daily), a selective, oral, nonsteroidal aromatase inhibitor, and megestrol acetate (40 mg four times daily), in postmenopausal women who progressed following tamoxifen treatment. PATIENTS AND METHODS Two randomized, double-blind for anastrozole, open-label for megestrol acetate, parallel-group, multicenter trials were conducted in 764 patients. Because both trials were identical in design, an analysis of the combined results was performed to strengthen interpretation of results from each trial. RESULTS The median follow-up duration was approximately 6 months. The estimated progression hazards ratios were 0.97 (97.5% confidence interval [CI], 0.75 to 1.24) for anastrozole 1 mg versus megestrol acetate and 0.92 (97.5% CI, 0.71 to 1.19) for anastrozole 10 mg versus megestrol acetate. The overall median time to progression was approximately 21 weeks. Approximately one third of patients in each group benefited from treatment. Twenty-seven patients (10.3%) in the anastrozole 1-mg group, 22 (8.9%) in the anastrozole 10-mg group, and 20 (7.9%) in the megestrol acetate group had a complete or partial response, and 66 (25.1%), 56 (22.6%), and 66 (26.1%) patients, respectively, had stable disease for > or = 24 weeks. For all end points, individual trial results were similar to the results of the combined analysis. Anastrozole and megestrol acetate were well tolerated. Gastrointestinal disturbance was more common among patients in the anastrozole groups than the megestrol acetate group; the difference between the anastrozole 10 mg and megestrol acetate groups was significant (P = .005). Significantly fewer patients in the anastrozole 1-mg (P < .0001) and 10-mg (P < .002) groups had weight gain than in the megestrol acetate group. More than 30% of megestrol acetate-treated patients had weight gain > or = 5%, and 10% of patients had weight gain > or = 10%. Patients who received megestrol acetate continued to gain weight over time. CONCLUSION Anastrozole, 1 and 10 mg once daily, is well tolerated and as effective as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment. Moreover, anastrozole therapy avoids the weight gain associated with megestrol acetate treatment.