Miracle-dz/UniFAR-FTUs huggingface dataset:
Boosting of HIV Protease Inhibitors by Ritonavir in the Intestine: The Relative Role of Cytochrome P450 and P-Glycoprotein Inhibition Based on Caco-2 Monolayers versus In Situ Intestinal Perfusion in Mice

HIV protease inhibitors are essential components of most recommended treatment regimens for HIV infection. They are always coadministered with ritonavir as a pharmacokinetic booster. Their bioavailability may be impaired because they are substrates of CYP3A4 and several transporters, including P-glycoprotein. The aim of this study was to explore the impact of ritonavir on the intestinal absorption of HIV protease inhibitors in two models: the Caco-2 system and the in situ intestinal perfusion model with mesenteric blood sampling in mice. Using the Caco-2 system, the effect of ritonavir on the permeability of the other HIV protease inhibitors was significant for saquinavir (2-fold increase) and indinavir (3-fold increase), negligible for darunavir and amprenavir, and nonexistent for nelfinavir, lopinavir, tipranavir, and atazanavir. However, performing the in situ intestinal perfusion technique in mice for three selected HIV protease inhibitors showed a significant increase in the intestinal permeability for all: indinavir (3.2-fold), lopinavir (2.3-fold), and darunavir (3-fold). The effect of aminobenzotriazole (a nonspecific cytochrome P450 inhibitor) on lopinavir permeability was comparable with using ritonavir, whereas there was no effect for indinavir and darunavir. We conclude that ritonavir can boost drug absorption by inhibiting P-glycoprotein and/or metabolism, in a compound-specific manner. The results of this study illustrate that a combination of absorption models needs to be considered to elucidate drug-drug interactions at the level of the intestinal mucosa.
Tissue-specific Expression of βKlotho and Fibroblast Growth Factor (FGF) Receptor Isoforms Determines Metabolic Activity of FGF19 and FGF21*

The fibroblast growth factor (FGF) 19 subfamily of ligands, FGF19, FGF21, and FGF23, function as hormones that regulate bile acid, fatty acid, glucose, and phosphate metabolism in target organs through activating FGF receptors (FGFR1–4). We demonstrated that Klotho and βKlotho, homologous single-pass transmembrane proteins that bind to FGFRs, are required for metabolic activity of FGF23 and FGF21, respectively. Here we show that, like FGF21, FGF19 also requires βKlotho. Both FGF19 and FGF21 can signal through FGFR1–3 bound by βKlotho and increase glucose uptake in adipocytes expressing FGFR1. Additionally, both FGF19 and FGF21 bind to the βKlotho-FGFR4 complex; however, only FGF19 signals efficiently through FGFR4. Accordingly, FGF19, but not FGF21, activates FGF signaling in hepatocytes that primarily express FGFR4 and reduces transcription of CYP7A1 that encodes the rate-limiting enzyme for bile acid synthesis. We conclude that the expression of βKlotho, in combination with particular FGFR isoforms, determines the tissue-specific metabolic activities of FGF19 and FGF21.
SybilGuard: defending against sybil attacks via social networks

Peer-to-peer and other decentralized, distributed systems are known to be particularly vulnerable to sybil attacks. In a sybil attack, a malicious user obtains multiple fake identities and pretends to be multiple, distinct nodes in the system. By controlling a large fraction of the nodes in the system, the malicious user is able to "out vote" the honest users in collaborative tasks such as Byzantine failure defenses. This paper presents SybilGuard, a novel protocol for limiting the corruptive influences of sybil attacks. Our protocol is based on the "social network" among user identities, where an edge between two identities indicates a human-established trust relationship. Malicious users can create many identities but few trust relationships. Thus, there is a disproportionately small "cut" in the graph between the sybil nodes and the honest nodes. SybilGuard exploits this property to bound the number of identities a malicious user can create. We show the effectiveness of SybilGuard both analytically and experimentally.
Phase calibration of hydrophones: heterodyne time-delay spectrometry and broadband pulse technique using an optical reference hydrophone

Two hydrophone calibration techniques are presented which provide amplitude and phase of hydrophone sensitivity. Heterodyne time-delay spectrometry can be applied in the frequency range from 0.5 to 50 MHz to all common hydrophones but needs a standard to obtain absolute values. A pulse technique between 1 and 70 MHz allows exploiting of an optical multilayer hydrophone as a phase standard. In combination with HTDS, a calibration service is established that covers the complete spectrum of common piezoelectric and optical hydrophones for absolute amplitude and phase calibration. The measured complex frequency responses form the basis of deconvolution procedures suitable for the correction of measurements of, for example, the output of ultrasound diagnostic machines.
Noise Aware and Combined Noise Models for Speech Denoising in Unknown Noise Conditions

Traditional denoising schemes require prior knowledge or statistics of the noise corrupting the signal, or estimate the noise from noise-only portions of the signal, which requires knowledge of speech boundaries. Extending denoising methods to perform well in unknown noise conditions can facilitate processing of data captured in different real life environments, and relax rigid data acquisition protocols. In this paper we propose two methods for denoising speech signals in unknown noise conditions. The first method has two stages. In the first stage we use Long Term Signal Variability features to decide which noise model to use from a pool of available models. Once we determine the noise type, we use Nonnegative Matrix Factorization with a dictionary trained on that noise to denoise the signal. In the second method, we create a combined noise dictionary from different types of noise, and use that dictionary in the denoising phase. Both of our systems improve signal quality, as measured by PESQ scores, for all the noise types we tested, and for different Signal to Noise Ratio levels.
Where optics meets electronics: recent progress in decreasing the terahertz gap

The terahertz region of the electromagnetic spectrum offers considerable opportunities for exploitation. Recent advances in source and coherent–detection technology have enabled advances to be made in a wide range of applications. This article reviews the historical development of the field, summarizes the current state of system technology and outlines a number of current system applications, including medical imaging. The limitations of present–day technology are discussed and some future possible applications are considered.
ADP Induced Surface Charge Changes of Adult and Newborn Platelets

In experiments reported here electrophoretic mobility of washed platelets and platelets suspended in diluted plasma obtained from adults and newborns was practically the same. No significant difference was observed in the pH—mobility relationship of the two types of platelets. These comparative studies indicate that the actual charge density, i.e. the number and sign of the charged groups at the newborn and adult platelet surfaces are essentially identical.
Systemic gene therapy of murine melanoma using tissue specific expression of the HSVtk gene involves an immune component.

Previously we have demonstrated safe and effective transfer of the HSVtk cytotoxic gene to primary murine melanoma tumors by direct injection of plasmid and retroviral vectors in which the HSVtk gene is driven by the tissue-specific tyrosinase promoter. However, for general clinical application such forms of therapy should, ideally, be effective against disseminated metastases. We report here that the number of recently established lung metastases of B16 melanoma in C57BL mice treated with ganciclovir is reduced compared to controls after multiple i.v. administrations of high titer retroviral supernatant encoding the HSVtk gene, but not after administration of liposome-complexed plasmid DNA. Using polymerase chain reaction analysis, integration of the provirus was observed in metastasis-bearing lungs (4 of 6 mice) and in the spleens of some ganciclovir-treated animals (2 of 6 mice) but not in the testes, brain, heart, liver, or kidney. The reduction in the number of experimental metastases in C57BL mice exceeded the anticipated extent of transduction of tumor cells, which is indicative of a marked bystander effect. This magnitude of reduction was not observed in immunodeficient athymic mice, suggesting that the immune system plays some part in the bystander effect. In support of these data, we show that, whereas the parental tumor cells are only poorly immunogenic, an effective antitumor immune response is generated following the killing of neoplastic cells in vivo as a result of treatment with ganciclovir. These effects may be responsible for augmenting the efficacy of retroviral infection. The combination of local cell killing by the HSVtk/ganciclovir system and the induction of antitumor immunity suggests new opportunities for the design of vectors for the gene therapy of cancer.
Du frottement à la tribologie : survol historique

L'article presente une breve histoire des recherches sur le frottement, accompagnee de quelques reflexions didactiques. Pour chaque periode, les themes et les resultats les plus importants sont illustres : les premieres lois et theories sur le frottement de Leonard DE VINCI jusqu'a AMONTONS et COULOMB ; les theories de la lubrification et les modeles du frottement de roulement, de 1840 a 1930 ; les theories de l'usure, la synthese de BOWDEN et de TABOR et la naissance de la tribologie ; les recents developpements, avec les nouveaux instruments de mesure et l'etude du frottement a l'echelle atomique, la nanotribologie.
Human Liver Aldehyde Oxidase: Inhibition by 239 Drugs

The authors tested 239 frequently used drugs and other compounds for their potential to inhibit the drug‐metabolizing enzyme, aldehyde oxidase, in human liver cytosol. A sensitive, moderate throughput HPLC‐MS assay was developed for 1‐phthalazinone, the aldehyde oxidase–catalyzed product of phthalazine oxidation. Inhibition of this activity was examined for the 239 drugs and other compounds of interest at a test concentration of 50 μM. Thirty‐six compounds exhibited greater than 80% inhibition and were further examined for measurement of IC50. The most potent inhibitor observed was the selective estrogen receptor modulator, raloxifene (IC50 = 2.9 nM), and tamoxifen, estradiol, and ethinyl estradiol were also potent inhibitors. Other classes of drugs that demonstrated inhibition of aldehyde oxidase included phenothiazines, tricyclic antidepressants, tricyclic atypical antipsychotic agents, and dihydropyridine calcium channel blockers, along with some other drugs, including loratadine, cyclobenzaprine, amodiaquine, maprotiline, ondansetron, propafenone, domperidone, quinacrine, ketoconazole, verapamil, tacrine, and salmeterol. These findings are discussed in context to potential drug interactions that could be observed between these agents and drugs for which aldehyde oxidase is involved in metabolism and warrant investigation of the possibility of clinical drug interactions mediated by inhibition of this enzyme.
Développement d'un imageur gamma haute résolution pour la cancérologie : du traitement chirurgical du cancer à l'étude sur petits animaux

Dans le cadre du traitement chirurgical du cancer, des sondes agissant comme des compteurs de radioactivite ont ete introduites en bloc operatoire pour assister en temps reel le chirurgien lors de l'ablation des tumeurs radio-marquees. Cette technique de radio-guidage permet d'acceder a la localisation precise et a l'ablation complete des tissus tumoraux. Pour renforcer cette pratique chirurgicale nous avons developpe une mini gamma-camera appelee POCI (Per-Operative Compact Imager). L'objectif de cette these etait de determiner l'apport de cette nouvelle generation de detecteur pour assister le chirurgien dans l'exerese des lesions tumorales et d'aborder egalement la cancerologie a travers les etudes in vivo sur petits animaux. Du point de vue instrumental, le principe de detection reposant sur une photodiode a localisation intensifiee valide par un premier prototype a ete etendu a l'imagerie a grande surface d'analyse avec la double contrainte de ne pas degrader les performances spatiales et de reduire l'encombrement de l'imageur. La camera ainsi realisee offre un champ de vue de 40mm de diametre et une masse de 1.2kg. A 140 keV, la resolution spatiale est de 2.1mm pour une efficacite de detection de 2.8 10^-4%. POCI a ete evalue a travers le protocole du ganglion sentinelle dans le cadre du cancer du sein selon deux approches : l'une basee sur une etude comparative des performances de detection d'une sonde et de POCI et l'autre reposant sur une evaluation clinique menee en collaboration avec l'Institut Gustave Roussy. Cette etude a permis d'etablir la complementarite entre POCI et la sonde en fonction des differentes configurations cliniques. Les performances de detection de POCI ont egalement ete evaluees chez la souris pour etudier la biodistribution de l'iode dans la thyroide et les glandes mammaires. L'ensemble de ces resultats prometteurs permet d'envisager l'utilisation du detecteur dans un plus large cadre d'investigations tant cliniques que biologiques.
Relationship between benzodiazepine receptor occupancy and functional effects in vivo of four ligands of differing intrinsic efficacies.

Agonists at the benzodiazepine receptor (BZR) produce their effects through potentiation of the inhibitory alpha-aminobutyric acid-mediated neurotransmission in the central nervous system via positive allosteric modulation of the gamma-aminobutyric acidA receptor. Agonists with high intrinsic efficacy are anticonvulsant, anxiolytic, muscle relaxant and sedative, whereas agonists with low intrinsic efficacy (partial agonists) are predominantly anticonvulsant and anxiolytic, but antagonize muscle relaxant and sedative effects of full agonists. The four BZR ligands triazolam, diazepam, Ro 19-8022 (a benzoquinolizinone) and bretazenil (Ro 16-6028, an imidazobenzodiazepinone) were pharmacologically characterized in various neurological and behavioral paradigms in mice: two anticonvulsant tests (prevention of audiogenic and pentylenetetrazol-induced seizures), a conflict test which reveals both anxiolytic and sedative properties and two tests which mainly measure motor impairment (rotarod and horizontal wire test). Although triazolam and diazepam elicited an effect in all tests, Ro 19-8022 and bretazenil exhibited anticonvulsant and anxiolytic properties, but virtually failed to induce motor impairment and severe sedation. In separate experiments, fractional BZR occupancy in vivo was assessed by inhibition of [3H]flumazenil binding and correlated with the pharmacological effects. Although diazepam and triazolam produced effects beginning at low to intermediate fractional BZR occupancy, Ro 19-8022 and bretazenil required a higher BZR occupancy to do so, in accordance with their partial agonistic character. With the two full agonists, anticonvulsant and anticonflict activities were elicited at a lower fractional BZR occupancy than muscle relaxant and sedative effects. (ABSTRACT TRUNCATED AT 250 WORDS)
The effects of risedronate on canine cancellous bone remodeling: Three‐dimensional kinetic reconstruction of the remodeling site

To investigate the dose‐dependent effects of risedronate on cancellous bone remodeling, adult female beagle dogs were treated with either placebo, 0.1, 0.5, or 2.5 mg/kg/day of risedronate orally in an intermittent cyclic regimen (7 days on 21 days off), repeated three times. Iliac cancellous bone samples were subjected to histomorphometric analysis and three‐dimensional (3‐D) kinetic reconstruction of the remodeling site was performed. In the 0.1 mg/kg dose group, resorption and activation indices were no different from the placebo group. However, wall thickness was increased resulting in a positive bone balance at the level of the remodeling unit. In the 0.5 and 2.5 mg/kg dose groups, a dose‐dependent reduction in activation frequency and tissue level bone formation was observed. Resorption rates were also significantly decreased, 60% and 80% for the 0.5‐ and 2.5‐mg/kg groups, respectively. An approximate 25% reduction in final erosion depth was noted in both these groups. Analyses of the growth curves of the bone packet confirmed that the kinetics of the growth of a completed packet were different in the 0.5‐ and 2.5‐mg/kg dose groups compared with placebo. These changes were associated with a significant increase in the final wall thickness in both groups indicating no net impairment of osteoblast function. These increases in wall thickness in combination with the reductions in final erosion depth in the 0.5 and 2.5 mg/kg groups resulted in a significant dose‐dependent positive bone balance. This pharmacological profile suggests that risedronate may be of therapeutic utility in the treatment of metabolic bone diseases where reductions in activation frequency and resorptive cell activity at the level of the remodeling unit are a therapeutic goal.
Low Serum Cultured Adipose Tissue-Derived Stromal Cells Ameliorate Acute Kidney Injury in Rats

Current studies suggest that mesenchymal stromal cells (MSCs) improve acute kidney injury (AKI) via paracrine/ endocrine effects. We established human adipose tissue-derived stromal cells (hASCs) cultured in low (2%) serum (hLASCs), which have great potential of tissue regeneration. The present study was performed to investigate the therapeutic effects of hLASCs on AKI and to clarify the mechanisms involved. In low serum, hASCs proliferated well, while human bone marrow-derived stromal cells (hBMSCs) did not. hLASCs secreted higher levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) than did hASCs cultured in high (20%) serum (hHASCs) or hBMSCs cultured in high serum (hHBMSCs). AKI was induced in nude rats by folic acid, and hLASCs, hHASCs or control medium were administered into the renal subcapsules. hLASCs significantly attenuated acute renal damage, while hHASCs showed far less effect. Furthermore, interstitial fibrosis observed on day 14 was less pronounced in the hLASCs group. Cell tracking experiment showed no evidence of transdifferentiation. Intravenous injection of hLASCs or hHBMSCs or subcapsular injection of hHBMSCs did not ameliorate AKI. Concerning the mechanisms, our in vivo experiments showed that HGF knockdown by siRNA impaired the ability of hLASCs to protect the kidney from acute injury whereas VEGF knockdown did not. In conclusion, hLASCs, but not hHASCs or hHBMSCs, ameliorated AKI via paracrine effects, and HGF is one of the key mediators.
On-line small disturbance voltage stability assessment in power systems based on wide area measurement

This paper presents a new fast method to detect the long term voltage instability of power system based on wide area measurement system (WAMS). The objective of this paper is to quickly assess the long term voltage instability, which may be occurred by load disturbance, using the measurements gathered from phasor measurement units (PMUs). The main features of this method is the preprocessing of the measured data using the mathematical morphology method, and classification of the chosen features using the support vector machine (SVM) to assess the voltage stability of power system. The simulation results have shown that the proposed method can effectively determine the voltage instability of power system at a very short time after the load disturbance.
Chopper-controlled PMDC motor drive using VHDL code

In many industrial applications it is necessary to convert a constant-voltage dc (direct current) source into a variable-voltage/variable-current source for the speed control of the dc motor drive. The variable dc voltage is controlled by chopping the input voltage by varying the on and off times of a converter, and the type of converter capable of such a function is known as a chopper. This work presents a chopper control using VHDL (very high speed integrated circuit hardware description language - VHSIC-HDL) language to control a PMDC motor (permanent magnetic direct current). The simulation is performed using two programs: MATLAB/Simulink and ModelSim, working in a co-simulation mode, provided by Link for ModelSim toolbox from Simulink. While the motor and inverter dynamics is performed in MATLAB, the control algorithm of the chopper runs in the ModelSim program. The simulation results are presented and analyzed in this work.
Is the Bayer DCA 2000 Acceptable as a Screening Instrument for the Early Detection of Renal Disease?

The analytical capabilities of the Bayer DCA 2000 System point-of-care instrument (Bayer Australia Ltd, Pyrnble, NSW, Australia) have recently been upgraded to include the measurement of the urine albumin.creatinine ratio (ACR). I Microalburninuria, defined as a urine ACR between 3-4 and 34 mg/rnrnol for females and between 2·5 and 34 for males," is a wellestablished predictor for diabetic nephropathy and clinical proteinuria in the non-diabetic. ' The use of the urine ACR measurement as a screening test for the early detection of renal disease in high-risk population groups, such as Aboriginal Australians, has recently been advocatcd.v" Through a co-operative partnership with the Umoona Tjutagku Health Service, the Renal Unit at Flinders Medical Centre has recently begun a program for the early detection and prevention of renal disease with the sOO-strong Umoona Aboriginal community at Coober Pedy in South Australia's far north. The first phase of the study involves screening the community for its risk factors for renal disease, the cornerstone of which is the measurement of urine ACR. The Bayer DCA 2000 instrument was selected as the instrument of choice for this phase of the program, but prior to its implementation, the analytical and diagnostic performance characteristics of the machine were evaluated.
The Variations of Chinese Jing Dialect

The separation between Chinese Jing dialect and Vietnamese has witnessed a history of almost 500 years. Today, Chinese Jing dialect is taking on considerable variations, not only in pronunciation and vocabulary but also in grammar. The variations of Chinese Jing dialect result not only from its internal reasons, but also from the influences of external language environment.
Microprocessor-based resistance measurement

The paper deals with microprocessor-based resistance measurement of electrical RL circuits by sampling values of the current and voltage. Special attention is paid to the relation between the time required for this measurement and the accuracy attained. This is a problem associated with circuits having a very high electrical time constant, such as windings of large transformers or superconducting coils. The suggested method permits shortening of the required resistance measurement time, which in turn realizes a significant overall time saving. In addition, it permits overcoming essential measurement errors which may occur when the test is performed during a thermal transient. Different measurement errors are analyzed and a statistical method which leads to significant improvement of the result is presented.