Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: An overview of biology and methodology

SummaryIn the past decade, research into P-glycoprotein involving the blood-brain barrier (BBB) has seen a shift in the concept of the BBB as a structural barrier to that of a functional barrier for xenobiotics and changed simultaneously the strategy for the discovery and development of drugs acting in the CNS. As far as making advances in neurotherapeutics are concerned, the brain-to-blood transport function at the BBB will be one of the most important issues. Knowing the limitations of thein vivo andin vitro methods for BBB efflux research, it is essential to adopt a multidisciplinary approach in investigating the true physiological role of the BBB. Among several methods, the Brain Efflux Index method and the use of conditionally immortalized brain capillary endothelial cell lines, established from transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen gene, are likely to be very useful tools for the BBB efflux transport research. According to our recent findings using these methods, several transporters in the brain capillary endothelial cells appear to play an important role in reducing the brain level of hydrophilic endogenous substrates produced either in the brain or peripheral organs, e.g., neurotransmitters, neuromodulators, metabolites of neurotransmitters, and uremic toxins. It has been reported also that large hydrophilic molecules, such as IgG, apo-transferrin, and amyloid-β peptide, are susceptible to brain-to-blood efflux transport. In the light of the latest findings, we have formed the hypothesis that the BBB acts as a CNS detoxifying system for both endogenous substrates and xenobiotics in the brain. A fuller understanding of the physiological role of BBB efflux transporters will provide rational insights to assist in the development of safer neurotherapeutics.
Motion Estimation Using Optical Flow Concepts

motion estimation is demanding field among researchers. The most general and challenging version of motion estimation is to compute an independent estimate of motion at each pixel, which is generally known as optical or optic flow. In our paper we have provided overview of some basic concepts behind optical flow and motion estimation. The paper is intended as starting point for beginners. Some common techniques and application of motion estimation is provided for the review of readers who are interested in this field.
Contractor Prequalification in Taiwan

It is very important for the project owner to screen out potential failure contractors from the bidding process. Contractor prequalification has been established as a standard practice in solving this problem. This study uses a prequalification that is a financial ratios model to assess the contractor's financial capability in Taiwan. Do not consider non-quantifiable factor, the model is effective in assessing the financial ability of construction contractors' selection.
Multi-Ray Channel Modeling and Wideband Characterization for Wireless Communications in the Terahertz Band

Terahertz (0.06-10 THz) Band communication is envisioned as a key technology for satisfying the increasing demand for ultra-high-speed wireless links. In this paper, first, a unified multi-ray channel model in the THz Band is developed based on ray tracing techniques, which incorporates the propagation models for the line-of-sight, reflected, scattered, and diffracted paths. The developed theoretical model is validated with the experimental measurements (0.06-1 THz) from the literature. Then, using the developed propagation models, an in-depth analysis on the THz channel characteristics is carried out. In particular, the distance-varying and frequency-selective nature of the Terahertz channel is analyzed. Moreover, the coherence bandwidth and the significance of the delay spread are studied. Furthermore, the wideband channel capacity using flat and water-filling power allocation strategies is characterized. Additionally, the temporal broadening effects of the Terahertz channel are studied. Finally, distance-adaptive and multi-carrier transmissions are suggested to best benefit from the unique relationship between distance and bandwidth. The provided analysis lays out the foundation for reliable and efficient ultra-high-speed wireless communications in the (0.06-10) THz Band.
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Efficient integration of sub-5-nm-gap plasmonic crystal cavities with plasmonic waveguides

We propose seamless integration of a tightly focused sub-5-nm-gap plasmonic crystal cavity with a plasmonic waveguide. A three-dimensionally tapered 2-nm-gap plasmonic crystal cavity exhibiting a mode volume of 6 × 10-6 (λ/n)3 can efficiently couple to an integrated waveguide with over 90% efficiency by optimally selecting the number of air-holes in the plasmonic crystal. Along with the theoretical study, we fabricated the three-dimensionally tapered plasmonic crystal cavity integrated with a waveguide by using e-beam-induced deposition and focused ion-beam milling techniques.
Bounding the Bias of Contrastive Divergence Learning

Optimization based on k-step contrastive divergence (CD) has become a common way to train restricted Boltzmann machines (RBMs). The k-step CD is a biased estimator of the log-likelihood gradient relying on Gibbs sampling. We derive a new upper bound for this bias. Its magnitude depends on k, the number of variables in the RBM, and the maximum change in energy that can be produced by changing a single variable. The last reflects the dependence on the absolute values of the RBM parameters. The magnitude of the bias is also affected by the distance in variation between the modeled distribution and the starting distribution of the Gibbs chain.
Multicolor Melting Curve Analysis-Based Multilocus Melt Typing of Vibrio parahaemolyticus

Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis outbreaks. To track the source of these diseases in a timely manner, a high throughput typing method is critical. We hereby describe a novel genotyping method for V. parahaemolyticus, termed multilocus melt typing (MLMT), based on multilocus sequence typing (MLST). MLMT utilizes melting curve analysis to interrogate the allelic types of a set of informative single nucleotide polymorphisms (SNPs) derived from the housekeeping genes used in MLST. For each SNP, one allelic type generates distinct Tm values, which are converted into a binary code. Multiple SNPs thus generate a series of binary codes, forming a melt type (MT) corresponding with a sequence type (ST) of MLST. Using a set of 12 SNPs, the MLMT scheme could resolve 218 V.parahaemolyticus isolates into 50 MTs corresponding with 56 STs. The discriminatory power of MLMT and MLST was similar with Simpson’s index of diversity of 0.638 and 0.646, respectively. The global (adjusted Rand index = 0.982) and directional congruence (adjusted Wallace coefficient, MT→ST = 0.965; ST→MT = 1.000) between the two typing approaches was high. The entire procedure of MLMT could be finished within 3 h with negligible hands on time in a real-time PCR machine. We conclude that MLMT provides a reliable and efficient approach for V. parahaemolyticus genotyping and might also find use in other pathogens.
The Study of NADPH-Dependent Flavoenzyme-Catalyzed Reduction of Benzo[1,2-c]1,2,5-oxadiazole N-Oxides (Benzofuroxans)

The enzymatic reactivity of a series of benzo[1,2-c]1,2,5-oxadiazole N-oxides (benzofuroxans; BFXs) towards mammalian single-electron transferring NADPH:cytochrome P-450 reductase (P-450R) and two-electron (hydride) transferring NAD(P)H:quinone oxidoreductase (NQO1) was examined in this work. Since the =N+ (→O)O− moiety of furoxan fragments of BFXs bears some similarity to the aromatic nitro-group, the reactivity of BFXs was compared to that of nitro-aromatic compounds (NACs) whose reduction mechanisms by these and other related flavoenzymes have been extensively investigated. The reduction of BFXs by both P-450R and NQO1 was accompanied by O2 uptake, which was much lower than the NADPH oxidation rate; except for annelated BFXs, whose reduction was followed by the production of peroxide. In order to analyze the possible quantitative structure-activity relationships (QSARs) of the enzymatic reactivity of the compounds, their electron-accepting potency and other reactivity indices were assessed by quantum mechanical methods. In P-450R-catalyzed reactions, both BFXs and NACs showed the same reactivity dependence on their electron-accepting potency which might be consistent with an “outer sphere” electron transfer mechanism. In NQO1-catalyzed two-electron (hydride) transferring reactions, BFXs acted as more efficient substrates than NACs, and the reduction efficacy of BFXs by NQO1 was in general higher than by single-electron transferring P-450R. In NQO1-catalyzed reactions, QSARs obtained showed that the reduction efficacy of BFXs, as well as that of NACs, was determined by their electron-accepting potency and could be influenced by their binding mode in the active center of NQO1 and by their global softness as their electronic characteristic. The reductive conversion of benzofuroxan by both flavoenzymes yielded the same reduction product of benzofuroxan, 2,3-diaminophenazine, with the formation of o-benzoquinone dioxime as a putative primary reductive intermediate, which undergoes a further reduction process. Overall, the data obtained show that by contrast to NACs, the flavoenzyme-catalyzed reduction of BFXs is unlikely to initiate their redox-cycling, which may argue for a minor role of the redox-cycling-type action in the cytotoxicity of BFXs.
Estimation of Vocal Tract Shape for VCV Syllables for a Speech Training Aid

Display of vocal tract shape can be used in speech training aids for the hearing impaired children, as it provides a visual feedback of the articulatory efforts. Estimation of vocal tract shape, based on LPC and other analysis techniques, works satisfactorily for vowels but generally fails during stop closures. Indication of correct place of articulation is very important, particularly for non-labial consonants. In order to study the dynamics of the vocal tract shape estimation during transitions at vowel-consonant boundaries, we have used "areagram", a spectrogram-like two-dimensional (2D) display of estimated vocal tract cross-sectional area as a function of time and position along the tract length. Area estimation is based on reflection coefficients obtained from LPC analysis of speech. Based on estimated area during the transition segments preceding and following the stop closure, bivariate polynomial surfaces are obtained and these are used for estimation of the vocal tract shape during stop closure by performing 2D interpolation. The place of closure for various stop consonants could be estimated satisfactorily from the conic surface approximation
Strategies for Sustainable Urban Transport: A Case Study of Cotonou, Benin

The unrestrained growth in urbanization and motorization generally contributes to an urban land use and transport system that is socially, economically, and environmentally unsustainable. Urban mobility systems are much diversified in developing countries taking into account their components in terms of transport modes and the development path linked to the urban growth. This paper uses Cotonou as a case study, which is the largest urban and economic city of Benin. The paper first reviews literatures on sustainable transport systems to comprehend the concept of sustainable development and transport. Based on the municipal development plan (MDP) adopted by the local authorities, the paper then evaluates the existing transport policies, projects and infrastructure system, to determine if the current paradigm is moving toward or away from sustainable transport. Furthermore, the principles for sustainable urban transport are developed to see what significance municipal transport policies have given to urban transport from a sustainable transport point of view. Finally some strategies are suggested, adoption of which may lead to a sustainable urban development and transport system in the city of Cotonou.Key words: Sustainable development; urbanization; Bus Rapid Transit; socio-economic; land use and urban transport system.
Health care provider challenges for reaching Hispanic immigrants with HPV vaccination in rural Georgia.

INTRODUCTION The objective of this pilot study was to understand, from the Vaccines for Children (VFC) program provider's perspective, issues relating to vaccine access and compliance for Hispanic adolescents in a rural setting. RESULTS Researchers conducted individual structured interviews with VFC providers and focus groups with Hispanic immigrant parents in rural southern Georgia. RESULTS Overall, the VFC providers said that their Hispanic patients were very positive toward vaccines in general, but there were cost issues related to stocking the vaccine and reaching the Hispanic population. The focus group discussions revealed that most Hispanic parents were not aware of the existence of the human papilloma virus (HPV) vaccine, nor had they heard about the VFC program. CONCLUSION Numerous vaccination barriers continue to impact HPV vaccine uptake in the Hispanic immigrant population in the US South.
The effect of polyamines on KATP channels in guinea‐pig ventricular myocytes

1 The effect of natural polyamines on KATP channels was studied using inside‐out patches from guinea‐pig ventricular myocytes. 2 At a holding potential of +40 mV, spermine at the intracellular membrane surface reduced the KATP channel open probability (Popen) in a dose‐dependent manner. Half‐maximal inhibition occurred at 29 μM with a Hill coefficient of 1.2. 3 The effect of spermine on Popen was not greatly influenced by the membrane potential but there appeared to be a small reduction in unitary current amplitude during strong depolarizations. 4 Analysis of KATP single channel kinetics showed that spermine inhibited the channel by decreasing the mean open time and introducing transitions to a long closed state. 5 Spermidine (0.1 mM) was found to have a similar effect to spermine. Putrescine (10 mM) was found to block more effectively at positive membrane potentials. Up to 20 mM arginine had no significant effect on KATP channels. 6 Our results indicate that natural polyamines influence native KATP channel gating in cardiac myocytes.
Pancreatic Cancer, A Mis-interpreter of the Epigenetic Language

Pancreatic cancer is the third leading cause of cancer mortality in the U.S. with close to 40,000 deaths per year. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90 percent of all pancreatic cancer cases and is the most lethal form of the disease. Current therapies for PDAC are ineffective and most patients cannot be treated by surgical resection. Most research efforts have primarily focused on how genetic alterations cause, alter progression, contribute to diagnosis, and influence PDAC management. Over the past two decades, a model has been advanced of PDAC initiation and progression as a multi-step process driven by the acquisition of mutations leading to loss of tumor suppressors and activation of oncogenes. The recognition of the essential roles of these genetic alterations in the development of PDAC has revolutionized our knowledge of this disease. However, none of these findings have turned into effective treatment for this dismal malignancy. In recent years, studies in the areas of chromatin modifications, and non-coding RNAs have uncovered mechanisms for regulating gene expression which occur independently of genetic alterations. Chromatin-based mechanisms are interwoven with microRNA-driven regulation of protein translation to create an integrated epigenetic language, which is grossly dysregulated in PDAC. Thus in PDAC, key tumor suppressors that are well established to play a role in PDAC may be repressed, and oncogenes can be upregulated secondary to epigenetic alterations. Unlike mutations, epigenetic changes are potentially reversible. Given this feature of epigenetic mechanisms, it is conceivable that targeting epigenetic-based events promoting and maintaining PDAC could serve as foundation for the development of new therapeutic and diagnostic approaches for this disease.
Explorer Mitochondrial changes within axons in multiple sclerosis

General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact openaccess@ed.ac. uk providing details, and we will remove access to the work immediately and investigate your claim. Summary Multiple sclerosis is the most common cause of non-traumatic neurological impairment in young adults. An energy deficient state has been implicated in the degeneration of axons, the pathological correlate of disease progression, in multiple sclerosis. Mitochondria are the most efficient producers of energy and play an important role in calcium homeostasis. We analysed the density and function of mitochondria using immunohistochemistry and histochemistry, respectively, in chronic active and inactive lesions in progressive multiple sclerosis. As shown before in acute pattern III and Balo's lesions, the mitochondrial respiratory chain complex IV activity is reduced despite the presence of mitochondria in demyelinated axons with amyloid precursor protein accumulation, which are predominantly located at the active edge of chronic active lesions. Furthermore, the strong non-phosphorylated neurofilament (SMI32) reactivity was associated with a significant reduction in complex IV activity and mitochondria within demyelinated axons. The complex IV defect associated with axonal injury may be mediated by soluble products of innate immunity, as suggested by an inverse correlation between complex IV activity and macrophage/microglial density in chronic lesions. However, in inactive areas of chronic multiple sclerosis lesions the mitochondrial respiratory chain complex IV activity and mitochondrial mass, judged by porin immunoreactivity, are increased within approximately half of large (>2.5 μm diameter) chronically demyelinated axons compared with large myelinated axons in the brain and spinal cord. The axon-specific mitochondrial docking protein (syntaphilin) and phosphorylated neurofilament-H were increased in chronic lesions. The lack of complex IV activity in a proportion of Na+/K+ ATPase α-1 positive demyelinated axons supports axonal dysfunction as a contributor to neurological impairment and disease progression. Furthermore, in vitro studies show that inhibition of complex IV augments glutamate-mediated axonal injury (amyloid precursor protein and SMI32 reactivity). Our findings have important implications for both axonal degeneration and dysfunction during the progressive stage of multiple sclerosis.
Developmental Sex Differences in Nicotinic Currents of Prefrontal Layer VI Neurons in Mice and Rats

Background There is a large sex difference in the prevalence of attention deficit disorder; yet, relatively little is known about sex differences in the development of prefrontal attention circuitry. In male rats, nicotinic acetylcholine receptors excite corticothalamic neurons in layer VI, which are thought to play an important role in attention by gating the sensitivity of thalamic neurons to incoming stimuli. These nicotinic currents in male rats are significantly larger during the first postnatal month when prefrontal circuitry is maturing. The present study was undertaken to investigate whether there are sex differences in the nicotinic currents in prefrontal layer VI neurons during development. Methodology/Principal Findings Using whole cell recording in prefrontal brain slice, we examined the inward currents elicited by nicotinic stimulation in male and female rats and two strains of mice. We found a prominent sex difference in the currents during the first postnatal month when males had significantly greater nicotinic currents in layer VI neurons compared to females. These differences were apparent with three agonists: acetylcholine, carbachol, and nicotine. Furthermore, the developmental sex difference in nicotinic currents occurred despite male and female rodents displaying a similar pattern and proportion of layer VI neurons possessing a key nicotinic receptor subunit. Conclusions/Significance This is the first illustration at a cellular level that prefrontal attention circuitry is differently affected by nicotinic receptor stimulation in males and females during development. This transient sex difference may help to define the cellular and circuit mechanisms that underlie vulnerability to attention deficit disorder.
Towards Development of a Circuit Based Treatment for Impaired Memory: A Multidisciplinary Approach

The previous decade saw progress in our understanding of fundamental neural systems of the brain, particularly those sub-serving memory. For example, it is now recognized that individual power and peak frequency attributes of alpha band rhythms predict performance on a working memory task. Additionally, investigators using transcranial magnetic stimulation (TMS), a safe and non-invasive means of stimulating the awake and alert human brain, have shown TMS can mimic long-term potentiation (LTP), widely considered the neurophysiologic substrate of memory. Based on this earlier work, we designed a combined TMS-EEG study of the effects of 10Hz rTMS on psychomotor processing speed, an index of neural efficiency, on a well validated short-term verbal recognition memory task, the Sternberg. We predicted first, that compared with sham 10Hz repetitive transcranial magnetic stimulation (rTMS) would significantly reduce psychomotor processing speed indexed as reaction time (RT). Second, we predicted that improvement in RT would be associated with a 10Hz rTMS induced increase in pre-task alpha power and pre-task alpha band phase synchrony.