Miracle-dz/UniFAR-FTUs huggingface dataset:
Contributions of Hepatic and Intestinal Metabolism to the Disposition of Niclosamide, a Repurposed Drug with Poor Bioavailability

Niclosamide, an antiparasitic, has been repositioned as a potential therapeutic drug for systemic diseases based on its antiviral, anticancer, and anti-infection properties. However, low bioavailability limits its in vivo efficacy. Our aim was to determine whether metabolic disposition by microsomal P450 enzymes in liver and intestine influences niclosamide’s bioavailability in vivo, by comparing niclosamide metabolism in wild-type, liver-Cpr-null (LCN), and intestinal epithelium-Cpr-null (IECN) mice. In vitro stability of niclosamide in microsomal incubations was greater in the intestine than in liver in the presence of NADPH, but it was much greater in liver than in intestine in the presence of UDPGA. NADPH-dependent niclosamide metabolism and hydroxy–niclosamide formation were inhibited in hepatic microsomes of LCN mice, but not IECN mice, compared with wild-type mice. In intestinal microsomal reactions, hydroxy–niclosamide formation was not detected, but rates of niclosamide-glucuronide formation were ∼10-fold greater than in liver, in wild-type, LCN, and IECN mice. Apparent Km and Vmax values for microsomal niclosamide–glucuronide formation showed large differences between the two tissues, with the intestine having higher Km (0.47 μM) and higher Vmax (15.8) than the liver (0.09 μM and 0.75, respectively). In vivo studies in LCN mice confirmed the essential role of hepatic P450 in hydroxy–niclosamide formation; however, pharmacokinetic profiles of oral niclosamide were only minimally changed in LCN mice, compared with wild-type mice, and the changes seem to reflect the compensatory increase in hepatic UDP-glucuronosyltransferase activity. SIGNIFICANCE STATEMENT These results suggest that efforts to increase the bioavailability of niclosamide by blocking its metabolism by P450 enzymes will unlikely be fruitful. In contrast, inhibition of niclosamide glucuronidation in both liver and intestine may prove effective for increasing niclosamide’s bioavailability, thereby making it practical to repurpose this drug for treating systemic diseases.
Exploitation of aeroelastic effects for drift reduction in an all-polymer air flow sensor

This paper presents a vibration amplitude measurement method that greatly reduces the effects of baseline resistance drift in an all-polymer piezoresistive flow sensor, or microtuft. The sensor fabrication is based on flexible printed circuit board (flex-PCB) technology to enable the potential for low-cost and scalable manufacture. Drift reduction is accomplished by discriminating the flow-induced vibration (‘flutter’) amplitude of the microtuft-based sensor as a function of flow velocity. Flutter peak-to-peak amplitude is measured using a microcontroller-based custom readout circuit. The fabricated sensor with the readout circuitry demonstrated a flow-referenced drift error of 0.2m/s of wind velocity per hour, a substantial improvement over previous sensors of this type using standard piezoresistive readout. The sensor has a sensitivity of 14.5mV/(m/s) with less than 1% non-linearity over the velocity range 5–16m/s.
Sociocultural influences on undergraduate students' conversations on race at a Predominantly White Institution

The purpose of this study was to analyze the sociocultural influences on dialogues about race of undergraduate students from various racial backgrounds at a Predominantly White Institution (PWI). This qualitative study included 16 undergraduate students from various racial backgrounds at a small, private university in the Midwest who participated in semi-structured focus group interviews. A data analysis addressed how the interplay of narratives and counter-narratives within dialogues on race revealed common themes within the framework of Critical Race Theory. Findings from the interview data suggest that race does not occur solely in the moment of a particular conversation or incidence. Rather, there are three sociocultural influences on undergraduates’ conversations on race: The collective history related to race in the United States, students’ personal experiences related to race, particularly discrimination, and the way they describe themselves as racial beings. Findings also revealed the possible benefits of providing spaces for students from various racial backgrounds to engage in dialogues on the construct of race.
Maternal Arterial Stiffness in Women Who Subsequently Develop Pre-Eclampsia

Background/Objectives Pre-eclampsia (PE) is associated with profound changes in the maternal cardiovascular system. The aim of the present study was to assess whether alterations in the maternal arterial stiffness precede the onset of PE in at risk women. Methodology/Principal Findings This was a cross sectional study involving 70 pregnant women with normal and 70 women with abnormal uterine artery Doppler examination at 22–24 weeks of gestation. All women had their arterial stiffness (augmentation index and pulse wave velocity of the carotid-femoral and carotid-radial parts of the arterial tree) assessed by applanation tonometry in the second trimester of pregnancy, at the time of the uterine artery Doppler imaging. Among the 140 women participating in the study 29 developed PE (PE group) and 111 did not (non-PE group). Compared to the non-PE group, women that developed PE had higher central systolic (94.9±8.6 mmHg vs 104.3±11.1 mmHg; p = <0.01) and diastolic (64.0±6.0 vs 72.4±9.1; p<0.01) blood pressures. All the arterial stiffness indices were adjusted for possible confounders and expressed as multiples of the median (MoM) of the non-PE group. The adjusted median augmentation index was similar between the two groups (p = 0.84). The adjusted median pulse wave velocities were higher in the PE group compared to the non-PE group (carotid-femoral: 1.10±0.14 MoMs vs 0.99±0.11 MoMs; p<0.01 and carotid-radial: 1.08±0.12 MoMs vs 1.0±0.11 MoMs; p<0.01). Conclusions/Significance Increased maternal arterial stiffness, as assessed by pulse wave velocity, predates the development of PE in at risk women.
Small-Molecule Inhibitors of the Receptor Tyrosine Kinases: Promising Tools for Targeted Cancer Therapies

Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK–TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK–TKIs have been developed for the treatment of cancer patients. Specific/selective RTK–TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK–TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.
Connectors for modeling object relations in CORBA-based systems

We present connectors as part of a conceptual design framework for modeling CORBA distributed object architectures. We propose the concept of connectors for abstracting complex object dependencies, and introduce connectors for CORBA object relations based on OMG's event service specification and relationship service specification. With connectors, modeling of component integration and interaction is strongly supported.
Coopetitive Ad Auctions

A single advertisement often benets many parties, for example, an ad for a Samsung laptop benets Microsoft. We study this phenomenon in search advertising auctions and show that standard solutions, including the status quo ignorance of mutual benet and a benet-aware Vickrey-Clarke-Groves mechanism, perform poorly. In contrast, we show that an appropriate rst-price auction has nice equilibria in a single-slot ad auction | all equilibria that satisfy a natural cooperative envy-freeness condition select the welfare-maximizing ad and satisfy an intuitive lower-bound on revenue.
Chemical bath deposition of textured and compact zinc oxide thin films on vinyl-terminated polystyrene brushes

In this study we investigated the influence of an organic polystyrene brush on the deposition of ZnO thin films under moderate conditions. On a non-modified SiOx surface, island growth is observed, whereas the polymer brush induces homogeneous film growth. A chemical modification of the polystyrene brushes during the mineralization process occurs, which enables stronger interaction between the then polar template and polar ZnO crystallites in solution. This may lead to oriented attachment of the crystallites so that the observed (002) texture arises. Characterization of the templates and the resulting ZnO films were performed with ζ-potential and contact angle measurements as well as scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). Infrared spectroscopy (IR) measurements were used to investigate the polystyrene brushes before and after modification.
Key figure impact in trust-enhanced recommender systems

Collaborative filtering recommender systems are typically unable to generate adequate recommendations for newcomers. Empirical evidence suggests that the incorporation of a trust network among the users of a recommender system can significantly help to alleviate this problem. Hence, users are highly encouraged to connect to other users to expand the trust network, but choosing whom to connect to is often a difficult task. Given the impact this choice has on the delivered recommendations, it is critical to guide newcomers through this early stage connection process. In this paper, we identify several classes of key figures in the trust network, namely mavens, frequent raters and connectors. Furthermore, we introduce measures to assess the influence of these users on the amount and the quality of the recommendations delivered by a trust-enhanced collaborative filtering recommender system. Experiments on a dataset from Epinions.com support the claim that generated recommendations for new users are more beneficial if they connect to an identified key figure compared to a random user.
CD8 Endows CD8 with Efficient Coreceptor Function by Coupling T Cell Receptor/CD3 to Raft-associated

The extraordinary sensitivity of CD8 (cid:3) T cells to recognize antigen impinges to a large extent on the coreceptor CD8. While several studies have shown that the CD8 (cid:2) chain endows CD8 with efficient coreceptor function, the molecular basis for this is enigmatic. Here we report that cell-associated CD8 (cid:4)(cid:2) , but not CD8 (cid:4)(cid:4) or soluble CD8 (cid:4)(cid:2) , substantially increases the avidity of T cell receptor (TCR)-ligand binding. To elucidate how the cytoplasmic and transmembrane portions of CD8 (cid:2) endow CD8 with efficient coreceptor function, we examined T1.4 T cell hybridomas transfected with various CD8 (cid:2) constructs. T1.4 hybridomas recognize a photoreactive Plasmodium berghei circumsporozoite (PbCS) peptide derivative (PbCS (4-azidobe-zoic acid [ABA])) in the context of H-2K d , and permit assessment of TCR-ligand binding by TCR photoaffinity labeling. We find that the cytoplasmic portion of CD8 (cid:2) , mainly due to its palmitoylation, mediates partitioning of CD8 in lipid rafts, where it efficiently associates with p56 lck . In addition, the cytoplasmic portion of CD8 (cid:2) mediates constitutive association of CD8 with TCR/CD3. The resulting TCR-CD8 adducts exhibit high affinity for major histocompatibility complex (MHC)-peptide. Importantly, because CD8 (cid:4)(cid:2) partitions in rafts, its interaction with TCR/CD3 promotes raft association of TCR/CD3. Engagement of these TCR/ CD3-CD8/lck adducts by multimeric MHC-peptide induces activation of p56 lck in rafts, which in turn phosphorylates CD3 and initiates T cell activation. column (Amersham Pharmacia Biotech) and used within 24 h. Experiments were performed at 25 (cid:13) C using HBS buffer (10 mM HEPES [pH 7.4], 150 mM NaCl, 3.4 mM EDTA, and 0.005% Surfactant P20; BIAcore) and a flow-rate of 10 (cid:9) l/ml.
Pathogenesis of a Pichinde Virus Strain Adapted to Produce Lethal Infections in Guinea Pigs

A model for studying the pathogenesis of virulent arenavirus infection was developed by adapting Pichinde virus to produce lethal infections of inbred guinea pigs. This adapted Pichinde virus retained low virulence for primates, thus potentially reducing the biohazard to investigators. Whereas all inbred (strain 13) guinea pigs were infected and killed by 3 plaque-forming units or more of adapted Pichinde virus injected subcutaneously, outbred (Hartley strain) guinea pigs were relatively resistant. All infected, inbred guinea pigs died at 13 to 19 days after inoculation, with viremias in excess of 5 log10 plaque-forming units/ml, severe lymphopenia (<1,000/mm3), and elevated serum glutamic oxaloacetic acid transaminase levels. Immunofluorescent antibody examination of tissues and infectivity titrations of tissue homogenates obtained at 3- to 4-day intervals demonstrated significant viral replication in all visceral tissues examined, but not in brain. Livers of all moribund guinea pigs contained moderate to severe hepatocellular necrosis and diffuse fatty change. Splenic red pulp and adrenal cortical tissues were engorged with blood and contained necrotic foci. Pancreatic acinar tissues were atrophied and vacuolated; lung sections typically contained areas of moderate to severe interstitial pneumonia. Inflammatory cells were conspicuously absent from all lesions. The virological and pathological features of adapted Pichinde infection in guinea pigs are remarkably similar to those described for Lassa virus infections in rhesus monkeys and humans, suggesting that this model might provide insight into the pathogenesis and treatment of Lassa fever in humans.
Iterative joint channel decoding of correlated sources employing serially concatenated convolutional codes

This correspondence looks at the problem of joint decoding of serially concatenated convolutional codes (SCCCs) used for channel coding of multiple correlated sources. We assume a simple model whereby two correlated sources transmit SCCC encoded data to a single destination receiver. We do not assume the existence of, nor do we use channel side information at the receiver. In particular, we present a novel iterative joint channel decoding algorithm for correlated sources by using the empirical cross-correlation measurements at successive decoding iterations to provide extrinsic information to the outer codes of the SCCC configuration. Two levels of soft metric iterative decoding are used at the receiver: 1) iterative maximum a posteriori probability (MAP) decoding is used for efficient decoding of individual SCCC codes (local iterations) and 2) iterative extrinsic information feedback generated from the estimates of the empirical cross correlation in partial decoding steps is used to pass soft information to the outer decoders of the global joint SCCC decoder (global iterations). We provide analytical results followed by simulation studies confirming the robustness of the cross-correlation estimates to channel-induced errors, justifying the use of such estimates in iterative decoding. Experimental results suggest that relatively few global iterations (two to five) during which multiple local iterations are conducted are sufficient to reap significant gains using this approach specially when the sources are highly correlated.
CBS: a concept-based sequencer for soundtrack composition

Existing methods of music composition vary from probability-based techniques to grammatical generation methods, yet the majority focus on the creation of independent pieces with no ties to other media. Our concept-based sequencer (CBS) aims to use semantic markup of temporal media in combination with genetic algorithms to generate music that can fit scripted content such as film and radio. Genetic algorithms offer an evolutionary approach, which allows mutation but within a specified context. The concept here allows for linkage between media. We describe the techniques behind the CBS, and the construction of a Web-based repository for concept mappings.
Nearest-neighbor estimation in sensor networks

This contribution reviews some recent advances in the field of nearest-neighbor (NN) nonparametric estimation in sensor networks. Upon observing X<sub>0</sub>, the problem is to estimate the corresponding response variable Y<sub>0</sub> by using the knowledge contained in a training set {(X<sub>i</sub>, Y<sub>i</sub>)}<sub>i</sub><sup>n</sup>=1, made of n independent copies of (X<sub>0</sub>, Y<sub>0</sub>). In the distributed version of the problem, a network made of spatially distributed sensors and a common fusion center (FC) is considered. As X<sub>0</sub> is made available at the FC, it is broadcast to all the sensors. Relying upon the locally available pair (X<sub>i</sub>, Y<sub>i</sub>) and upon X<sub>0</sub>, sensor i sends a message containing Y<sub>i</sub> to the FC, or stays silent: only the few most informative response variables {Y<sub>i</sub>} should be sent, but no inter-sensor coordination is allowed. The analysis is asymptotic in the limit of large network size n and we show that, by means of a suitable ordered transmission policy, only a vanishing fraction of NN messages can be selected, yet preserving the consistency of the estimation even under communication constraints.
Sonication-assisted Metal-enhanced Fluorescence-based Bioassays

A new bioassay technique, sonication-assisted metal-enhanced fluorescence, which is based on the combined use of ultrasound waves and metal-enhanced fluorescence (MEF), is reported. In this technique, low-intensity ultra-sound waves significantly reduce the bioassay time by creating a temperature gradient between the bulk and the surface, which is thought to result in a mass transport of biomolecules from the bulk to the surface. After the assay is completed in 1 min, fluorescence emission is enhanced due to the MEF phenomenon. For proof-of-concept, a model bioassay based on the interactions of biotin and fluorophore-labeled avidin was constructed on SIFs and was subsequently completed in <1 min using low-intensity ultrasound at 40 kHz. The end-point values for fluorescence emission from sonicated assays were compared to those measured from assays carried out at room temperature without sonication to confirm to accuracy of the new technique. The effect of sonication on the assay components were studied using optical absorption spec-troscopy, atomic force microscopy, and fluorescence spectroscopy techniques. Real-time thermal imaging was used to measure the changes in temperature of the bioassay components during the sonication process. Fluorescence resonance energy transfer (FRET) was also employed to investigate the effect of sonication on potential surface protein denaturation and conformational changes. The identification and quantification of proteins and other biomolecules using bioassays are of great importance in biomedi-cal and biochemical applications. 1-3 Fluorescence is the dominant technology in most of these applications, where a biomolecule of interest is detected by fluorescence emission from its fluorophore-labeled binding partner. 4,5 Fluorescence-based bioassays carried out on planar surfaces generally lack sensitivity and require expensive optical instruments. 6,7 In addition, the biorecognition events in these assays are inherently slow (several minutes to hours). 6,7 The sensitivity of the fluorescence-based assays can be improved, without the use of high-end optical instruments, by incorporating plasmon resonant particles (PSPs) into these assays. 8,9 The improved sensitivity is made possible by the increase in fluorescence signatures and decreased lifetimes of fluorophores placed in close proximity to PSPs, described by a phenomenon called metal-enhanced fluorescence (MEF). 8,10 In MEF-based bioassays, PSPs (generally silver nanoparticles) are deposited onto the planar surface and the bioassay is constructed on the PSPs. 8 Since the size of most biomolecules are smaller than PSPs (20-100 nm), fluorophores are positioned within a distance where their emission is increased due to their interactions and the generation of surface plasmons in PSPs. 10 Although the …
Termination of Graph Rewriting is Undecidable

It is shown that it is undecidable in general whether a graph rewriting system (in the “double pushout approach”) is terminating. The proof is by a reduction of the Post Correspondence Problem. It is also argued that there is no straightforward reduction of the halting problem for Turing machines or of the termination problem for string rewriting systems to the present problem.
Electron microscopic studies of magnetosomes in magnetotactic bacteria

Electron microscopic studies on magnetosomes in magnetotactic bacteria have revealed much information on their composition, structure, and even the formation of their mineral phase. The mineral phases of the magnetosomes are of two general types: iron oxides and iron sulfides. Iron oxide‐type magnetosomes contain particles of the ferrimagnetic mineral magnetite (Fe3O4) while the iron sulfide‐type contain ferrimagnetic greigite (Fe3S4), greigite and non‐magnetic pyrite (FeS2), or possibly ferrimagnetic pyrrhotite (Fe7S8). Regardless of their composition, the crystalline particles in magnetosomes have a narrow size range: approximately 35 to 120 nm. Magnetite crystals in this size range are single‐magnetic‐domains and confer a permanent magnetic dipole moment to the cell. The single‐domain size range for greigite is not known but is probably similar to that for magnetite.