Miracle-dz/UniFAR-FTUs huggingface dataset:
The Small Molecule Indirubin-3'-Oxime Inhibits Protein Kinase R: Antiapoptotic and Antioxidant Effect in Rat Cardiac Myocytes

Double-stranded, RNA-dependent protein kinase R (PKR) is a serine/threonine protein kinase activated by various stress signals. It plays an important role in inflammation, insulin sensitivity and glucose homeostasis. Increased PKR activity has been observed in obese humans as well as in obese diabetic mice. Indirubin-3'-oxime (I3O) is an effective inhibitor of cyclin-dependent kinases and glycogen synthase kinase 3-beta. However, the effects of I3O on PKR activity/expression in cultured rat cardiomyocytes have not been reported. We investigated whether I3O attenuates the effects of high glucose on PKR, oxidative stress and apoptotic gene markers. Quantitative PCR and western blotting were used to measure protein and mRNA, respectively. High glucose treatment caused significant increase in the PKR protein/mRNA expression, which was attenuated by co-treatment with I3O. High glucose-treated, cultured cardiomyocytes developed a significant increase in mRNA expression for c-Jun-N-terminal kinase, caspase-3 and NF-κB, which were all attenuated by pretreatment with I3O. There was also a significant increase in reactive oxygen species generation in high glucose-treated, cultured cardiomyocytes, which was attenuated by pretreatment with I3O. In conclusion, I3O may have a preventive role against the deleterious effects of high glucose in the heart.
Lipoprotein(a): resurrected by genetics

Plasma lipoprotein(a) [Lp(a)] is a quantitative genetic trait with a very broad and skewed distribution, which is largely controlled by genetic variants at the LPA locus on chromosome 6q27. Based on genetic evidence provided by studies conducted over the last two decades, Lp(a) is currently considered to be the strongest genetic risk factor for coronary heart disease (CHD). The copy number variation of kringle IV in the LPA gene has been strongly associated with both Lp(a) levels in plasma and risk of CHD, thereby fulfilling the main criterion for causality in a Mendelian randomization approach. Alleles with a low kringle IV copy number that together have a population frequency of 25–35% are associated with a doubling of the relative risk for outcomes, which is exceptional in the field of complex genetic phenotypes. The recently identified binding of oxidized phospholipids to Lp(a) is considered as one of the possible mechanisms that may explain the pathogenicity of Lp(a). Drugs that have been shown to lower Lp(a) have pleiotropic effects on other CHD risk factors, and an improvement of cardiovascular endpoints is up to now lacking. However, it has been established in a proof of principle study that lowering of very high Lp(a) by apheresis in high‐risk patients with already maximally reduced low‐density lipoprotein cholesterol levels can dramatically reduce major coronary events.
Emotional processing and executive functioning in children and adults with Tourette's syndrome

Tourette's syndrome (TS) is predominantly a childhood disorder, with many of those who meet diagnostic criteria in childhood experiencing a remission of symptoms in adulthood. This indicates that the influence of TS on cognitive and emotional processing can best be understood by examining performance in both adults and children with TS. The present study examined emotional processing using a battery of face and prosody tasks with increasing levels of difficulty (same-different emotion discrimination, emotion naming, and emotion naming with conflict for prosody only). Experiment 1 compared the performance of children with TS-alone (n = 16) or TS+ADHD (n = 15) to healthy matched control children (n = 27). Compared to healthy control children, no significant group differences were found for those with TS-alone. Children with TS+ADHD showed subtle impairments on the more difficult emotion processing tasks relative to healthy control children, and differences were more pronounced for anger items (voice emotion naming, p < .05; voice emotion naming with conflict, p < .01). Experiment 2 compared the performance of adults with TS-alone (n = 23) to healthy matched controls (n = 21). No significant group differences were found, other than evidence of subtle impairment in the adults with TS-alone on the most complex task, again particularly for anger items (p < .05). Separate measurement of executive skills detected no evidence of impairment in children or adults with TS and little in the way of correlational evidence linking emotion recognition and executive skills. Implications of the findings for our understanding of emotion processing in TS are discussed.
Design Optimization on Conductor Placement in the Slot of Permanent Magnet Machines to Restrict Turn–Turn Short-Circuit Fault Current

In permanent magnet (PM) machines, a turn-turn short-circuit (SC) fault is the most critical fault to eradicate. The fault introduces high SC current in the shorted turn, which may consequently lead to secondary faults unless the fault is appropriately controlled. This paper proposes feasible conductors' placement in a slot of a PM machine to minimize such turn-turn fault current. In order to minimize the fault current, the conductor arrangement in a slot is optimized using a multi-objective genetic algorithm incorporating with both analytical and finite-element numerical tool. The possible combinations of conductors' placement are set as variables and optimized for a given machine, which is designed for safety critical applications. It is shown that the fault current associated with a single turn fault can be significant for the random winding placement, even though the remedial strategies are put in place. It is also shown that the fault current can be significantly limited by rearranging the winding placement in a way to share slot-leakage fluxes. This is confirmed via experiment on E-core. Influences of the winding arrangement on both frequency-dependent resistances and winding's capacitances are experimented. It is demonstrated that adopting the winding arrangement that shares the slot-leakage flux effectively benefits to minimize the ac losses in addition to improved fault tolerance. But it increases the turn-turn capacitances whose effect, however, can be neglected as the resonance frequency occurs beyond the operational frequency range of the machines of interest.
Prime time for minor subunits of the type II secretion and type IV pilus systems

The type II secretion system (T2SS) exports folded proteins from the periplasms of Gram‐negative bacteria. The type IV pilus system (T4PS) is a multifunctional machine used for adherence, motility and DNA transfer in bacteria and archaea. Partial sequence identity between the two systems suggests that they are related and might function via a similar mechanism, the dynamic assembly and disassembly of pseudopilus (T2SS) or pilus (T4PS) filaments. The major subunit in each system is thought to form the bulk of the (pseudo)pilus, while minor (low‐abundance) subunits have proposed roles in assembly initiation, antagonism of disassembly, or modulation of (pseudo)pilus functional properties. In this issue, Cisneros et al. ( ) extend their previous finding that pseudopilus assembly is primed by the minor pseudopilins, showing that the same proteins can initiate assembly of Escherichia coli T4P. Similarly, they show that the E. coli minor pilins prime the polymerization of T2S pseudopili, although unlike genuine pseudopili, the chimeric filaments did not support secretion. This work reinforces the notion of a common assembly mechanism for the T2S and T4P systems.
Prevention of carcinogenesis by protease inhibitors.

Protease inhibitors are very effective in their ability to suppress carcinogenesis in many different in vivo and in vitro assay systems. One particularly effective protease inhibitor, the soybean-derived Bowman-Birk inhibitor, has been extensively studied in our laboratory. Our results have indicated that Bowman-Birk inhibitor suppresses carcinogenesis 1) induced by several different types of carcinogens, 2) in three different species (mice, rats, and hamsters), 3) in several different tissues/organs [colon, liver, lung, esophagus, and cheek pouch (oral epithelium)], 4) when administered to animals by several different routes (including the diet), 5) involving several different types of tumors (squamous cell carcinomas, adenocarcinomas, angiosarcomas, etc.) and 6) in different cell types [epithelial cells (in the colon, liver, lung, esophagus, and cheek pouch) as well as connective tissue cells (fibroblasts, both in vitro and those in the liver which give rise to angiosarcomas)]. Thus, the remarkable ability of Bowman-Birk inhibitor to serve as an anticarcinogenic agent has been demonstrated in a variety of different carcinogenesis assay systems. Although the mechanism of action of protease inhibitors as anticarcinogenic agents is unknown, many hypotheses have been presented. Our results suggest that anticarcinogenic protease inhibitors are capable of reversing the initiating event in carcinogenesis, presumably by stopping an ongoing process begun by carcinogen exposure. We have observed several effects of protease inhibitors which are thought to be related to their anticarcinogenic activity; these include 1) the ability to affect the expression of certain oncogenes (e.g., c-myc and c-fos) and 2) the ability to affect the levels of certain types of proteolytic activities (e.g., N-t-butoxycarbonyl-Val-Pro-Arg-7-amino-4-methylcoumarin-hydrolyzing activity) which are elevated in carcinogen-exposed tissues. We have also observed other effects of anticarcinogenic protease inhibitors which may be related to carcinogenesis. For example, we have reported that the inhibitors can reduce the carcinogen-induced, elevated levels of gene amplification to nearly normal levels. While all of these effects of protease inhibitors may contribute to the prevention of carcinogenesis, the mechanism by which protease inhibitors prevent cancer cannot be determined with certainty until the mechanisms involved in cancer induction are known. While the mechanism remains unclear, it is clear that protease inhibitors can reverse a number of carcinogen-induced cellular changes which may play important roles in carcinogenesis.
A Quasi-linearisation approach to trajectory based methods for nonlinear MOR

Model Order Reduction (MOR) techniques are means to find low dimensional approximations of large dynamical systems for applications in simulation and control. Trajectory based methods are a class of MOR techniques for nonlinear systems wherein multiple linearisations along a training trajectory are superposed to approximate the system dynamics. Although standard trajectory based methods generally work well, there are instances which require specific modifications in the approach. In this work, we propose a modification of the conventional technique for systems with nonlinear input operators. The modified method involves a quasi-linearisation of the nonlinear system and subsequent MOR and superposition. It is applied to a nonlinear circuit model for which conventional trajectory based methods have been found ineffective. The results obtained show a considerable improvement in the reproduction of the nonlinear system dynamics.
The influence of classroom openness and citizenship efficacy on adolescents' civic behaviour: The Hong Kong case

In recent years, Hong Kong has actively participated in such international research projects as the International Civic and Citizenship Education Study 2009 (ICCS 2009), organised by the International Association for the Evaluation of Educational Achievement (IEA), with the aim of learning more about the performance of Hong Kong students in different spheres. Such international studies generate invaluable data with a scope beyond that which any individual researcher could achieve. Secondary analysis of this data helps inform policies and practices. In this study, the Hong Kong sample from the ICCS 2009 was subjected to secondary analysis. The sample comprised 2,902 junior secondary students with a mean age of 14.3 years. The sample was used for the investigation of adolescents’ civic behaviour, and to identify the factors that contribute to such behaviour. The schools were chosen for the ICCS 2009 study through stratified random sampling and an intact class from each chosen The Hong Kong Institute of Education Library For private study or research only. Not for publication or further reproduction. v school was surveyed. This study built on social cognitive theory to develop a conceptual model of the effects of the classroom climate on students’ selfreported civic behaviour. The study then tested the model using a two-step multilevel structural equation model. The results showed that the classroom climate had both direct and indirect effects on adolescents’ civic behaviour at both the studentand class-level. This study contributes to the application of social cognitive theory using secondary data and demonstrates how this theory can be used for research into adolescents’ civic behaviour. By adopting a twostage approach, five sets of plausible values were established for each scale developed using item response theory (IRT). Multilevel structural equation modelling (MSEM) was then used. The hypothetical model, based on social cognitive theory, was examined and the implications of the model discussed. This study can stimulate future research to explore more deeply the influences on adolescents exerted by different people in their social lives. Further, the secondary data analysis in this study identified different scale structures from the international scales identified by the IEA. It can therefore provide insights that are beneficial to future research on local contexts using the ICCS 2009 data. The Hong Kong Institute of Education Library For private study or research only. Not for publication or further reproduction.
Heterologous expression and coupling of G protein‐gated inwardly rectifying K+ channels in adult rat sympathetic neurons

1 G protein‐gated inwardly rectifying K+ (GIRK) channels were heterologously expressed in rat superior cervical ganglion (SCG) neurons by intranuclear microinjection. The properties of GIRK channels and their coupling to native receptors were characterized using the whole‐cell patch‐clamp technique. 2 Following coinjection of either GIRK1–2 or GIRK1–4 cDNA, application of noradrenaline (NA) produced large inwardly rectifying K+ currents. Injection of cDNA encoding individual GIRK subunits produced only small and inconsistent NA‐activated inward currents. Current arising from the native expression of GIRK channels in SCG neurons was not observed. 3 NA‐mediated activation of GIRK channels was abolished by pertussis toxin (PTX) pretreatment, indicating coupling via G proteins of the Gi/Go subfamily. Conversely, vasoactive intestinal peptide (VIP) activated GIRK channel currents via a cholera toxin‐sensitive pathway suggesting coupling through Gαs. Pretreatment of neurons with PTX caused a significant increase in amplitude of the VIP‐mediated GIRK channel currents when compared with untreated cells. 4 Application of adenosine, prostaglandin E2 and somatostatin resulted in activation of GIRK channel currents. Activation of m1 muscarinic acetylcholine receptors (i.e. application of oxotremorine m to PTX‐treated neurons) failed to elicit overt GIRK channel currents. 5 GIRK channel overexpression decreased basal Ca2+ channel facilitation significantly when compared with uninjected neurons. Furthermore, the NA‐mediated inhibition of Ca2+ channels was significantly attenuated. 6 In summary, the ability to heterologously express GIRK channels in adult sympathetic neurons allows the experimental alteration of receptor‐G protein‐effector stoichiometry. Such studies may increase our understanding of the mechanisms underlying ion channel modulation by G proteins in a neuronal environment.
Altered Fine Structures of Corneal and Skeletal Keratan Sulfate and Chondroitin/Dermatan Sulfate in Macular Corneal Dystrophy*

The content and fine structure of keratan and chondroitin/dermatan sulfate in normal human corneas and corneas affected by macular corneal dystrophies (MCD) types I and II were examined by fluorophore-assisted carbohydrate electrophoresis. Normal tissues (n = 11) contained 15 μg of keratan sulfate and 8 μg of chondroitin/dermatan sulfate per mg dry weight. Keratan sulfates consisted of ∼4% unsulfated, 42% monosulfated, and 54% disulfated disaccharides with number of average chain lengths of ∼14 disaccharides. Chondroitin/dermatan sulfates were significantly longer, ∼40 disaccharides per chain, and consisted of ∼64% unsulfated, 28% 4-sulfated, and 8% 6-sulfated disaccharides. The fine structural parameters were altered in all diseased tissues. Keratan sulfate chain size was reduced to 3–4 disaccharides; chain sulfation was absent in MCD type I corneas and cartilages, and sulfation of both GlcNAc and Gal was significantly reduced in MCD type II. Chondroitin/dermatan sulfate chain sizes were also decreased in all diseased corneas to ∼15 disaccharides, and the contents of 4- and 6-sulfated disaccharides were proportionally increased. Tissue concentrations (nanomole of chains per mg dry weight) of all glycosaminoglycan types were affected in the disease types. Keratan sulfate chain concentrations were reduced by ∼24 and ∼75% in type I corneas and cartilages, respectively, and by ∼50% in type II corneas. Conversely, chondroitin/dermatan sulfate chain concentrations were increased by 60–70% in types I and II corneas. Such changes imply a modified tissue content of individual proteoglycans and/or an altered efficiency of chain substitution on the core proteins. Together with the finding that hyaluronan, not normally present in healthy adult corneas, was also detected in both disease subtypes, the data support the conclusion that a wide range of keratocyte-specific proteoglycan and glycosaminoglycan remodeling processes are activated during degeneration of the stromal matrix in the macular corneal dystrophies.
Host sanctions and pollinator cheating in the fig tree–fig wasp mutualism

Theory predicts that mutualisms should be vulnerable to invasion by cheaters, yet mutualistic interactions are both ancient and diverse. What prevents one partner from reaping the benefits of the interaction without paying the costs? Using field experiments and observations, we examined factors affecting mutualism stability in six fig tree–fig wasp species pairs. We experimentally compared the fitness of wasps that did or did not perform their most basic mutualistic service, pollination. We found host sanctions that reduced the fitness of non-pollinating wasps in all derived, actively pollinated fig species (where wasps expend time and energy pollinating), but not in the basal, passively pollinated fig species (where wasps do not). We further screened natural populations of pollinators for wasp individuals that did not carry pollen (‘cheaters’). Pollen-free wasps occurred only in actively pollinating wasp species, and their prevalence was negatively correlated with the sanction strength of their host species. Combined with previous studies, our findings suggest that (i) mutualisms can show coevolutionary dynamics analogous to those of ‘arms races’ in overtly antagonistic interactions; (ii) sanctions are critical for long-term mutualism stability when providing benefits to a host is costly, and (iii) there are general principles that help maintain cooperation both within and among species.
Phakopsora pachyrhizi, the causal agent of Asian soybean rust.

UNLABELLED The plant pathogenic basidiomycete fungi Phakopsora pachyrhizi and Phakopsora meibomiae cause rust disease in soybean plants. Phakopsora pachyrhizi originated in Asia-Australia, whereas the less aggressive P. meibomiae originated in Latin America. In the New World, P. pachyrhizi was first reported in the 1990s to have spread to Hawaii and, since 2001, it has been found in South America. In 2004, the pathogen entered continental USA. This review provides detailed information on the taxonomy and molecular biology of the pathogen, and summarizes strategies to combat the threat of this devastating disease. TAXONOMY Phakopsora pachyrhizi Syd. & P. Syd; uredial anamorph: Malupa sojae (syn. Uredo sojae); Domain Eukaryota; Kingdom Fungi; Phylum Basidiomycota; Order Uredinales; Class Urediniomycetes; Family Phakopsoraceae; Genus Phakopsora (http://www.indexfungorum.org). The nomenclature of rust spores and spore-producing structures used within this review follows Agrios GN (2005) Plant Pathology, 5th edn. London: Elsevier/Academic Press. HOST RANGE In the field, P. pachyrhizi infects leaf tissue from a broad range (at least 31 species in 17 genera) of leguminous plants. Infection of an additional 60 species in other genera has been achieved under laboratory conditions. DISEASE SYMPTOMS At the beginning of the disease, small, tan-coloured lesions, restricted by leaf veins, can be observed on infected soybean leaves. Lesions enlarge and, 5-8 days after initial infection, rust pustules (uredia, syn. uredinia) become visible. Uredia develop more frequently in lesions on the lower surface of the leaf than on the upper surface. The uredia open with a round ostiole through which uredospores are released.
Detection and decomposition algorithm for dual logic implementations

Based on the disjointed cubes of the logic functions, a method using hamming distance to detect logic functions suitable for Reed-Muller(RM) logic implementation is presented. And the original covers of the logic functions are decomposed into two parts. One is suitable for RM logic implementation and the other is suitable for Boolean logic implementation. The proposed algorithm is implemented in C and tested on MCNC benchmarks. The experimental results show that the proposed algorithm is efficient compared with published methods.
Association between pre-eclampsia and locally derived traffic-related air pollution: a retrospective cohort study

Background Pre-eclampsia is a common complication of pregnancy and is a major cause of fetal–maternal mortality and morbidity. Despite a number of plausible mechanisms by which air pollutants might contribute to this process, few studies have investigated the association between pre-eclampsia and traffic emissions, a major contributor to air pollution in urban areas. Objective The authors investigated the association between traffic-related air pollution and risk of pre-eclampsia in a maternal population in the urban centre of Perth, Western Australia. Method The authors estimated maternal residential exposure to a marker for traffic-related air pollution (nitrogen dioxide, NO2) during pregnancy for 23 452 births using temporally adjusted land-use regression. Logistic regression was used to investigate associations with pre-eclampsia. Results Each IQR increase in levels of traffic-related air pollution in whole pregnancy and third trimester was associated with a 12% (1%–25%) and 30% (7%–58%) increased risk of pre-eclampsia, respectively. The largest effect sizes were observed for women aged younger than 20 years or 40 years or older, aboriginal women and women with pre-existing and gestational diabetes, for whom an IQR increase in traffic-related air pollution in whole pregnancy was associated with a 34% (5%–72%), 35% (0%–82%) and 53% (7%–219%) increase in risk of pre-eclampsia, respectively. Conclusions Elevated exposure to traffic-related air pollution in pregnancy was associated with increased risk of pre-eclampsia. Effect sizes were highest for elevated exposures in third trimester and among younger and older women, aboriginal women and women with diabetes.