Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Potential Molecular Contributors to Atrial Hypocontractility Caused by Atrial Tachycardia Remodeling in Dogs

Background—Atrial fibrillation impairs atrial contractility, inducing atrial stunning that promotes thromboembolic stroke. Action potential (AP)-prolonging drugs are reported to normalize atrial hypocontractility caused by atrial tachycardia remodeling (ATR). Here, we addressed the role of AP duration (APD) changes in ATR-induced hypocontractility. Methods and Results—ATR (7-day tachypacing) decreased APD (perforated patch recording) by ≈50%, atrial contractility (echocardiography, cardiomyocyte video edge detection), and [Ca2+]i transients. ATR AP waveforms suppressed [Ca2+]i transients and cell shortening of control cardiomyocytes; whereas control AP waveforms improved [Ca2+]i transients and cell shortening in ATR cells. However, ATR cardiomyocytes clamped with the same control AP waveform had ≈60% smaller [Ca2+]i transients and cell shortening than control cells. We therefore sought additional mechanisms of contractile impairment. Whole-cell voltage clamp revealed reduced ICaL; ICaL inhibition superimposed on ATR APs further suppressed [Ca2+]i transients in control cells. Confocal microscopy indicated ATR-impaired propagation of the Ca2+ release signal to the cell center in association with loss of t-tubular structures. Myofilament function studies in skinned permeabilized cardiomyocytes showed altered Ca2+ sensitivity and force redevelopment in ATR, possibly due to hypophosphorylation of myosin-binding protein C and myosin light-chain protein 2a (immunoblot). Hypophosphorylation was related to multiple phosphorylation system abnormalities where protein kinase A regulatory subunits were downregulated, whereas autophosphorylation and expression of Ca2+-calmodulin-dependent protein kinase II&dgr; and protein phosphatase 1 activity were enhanced. Recovery of [Ca2+]i transients and cell shortening occurred in parallel after ATR cessation. Conclusions—Shortening of APD contributes to hypocontractility induced by 1-week ATR but accounts for it only partially. Additional contractility-suppressing mechanisms include ICaL current reduction, impaired subcellular Ca2+ signal transmission, and altered myofilament function associated with abnormal myosin and myosin-associated protein phosphorylation. The complex mechanistic basis of the atrial hypocontractility associated with AF argues for upstream therapeutic targeting rather than interventions directed toward specific downstream pathophysiological derangements.
Insights into the red algae and eukaryotic evolution from the genome of Porphyra umbilicalis (Bangiophyceae, Rhodophyta)

Significance Fossil evidence shows that red algae (Rhodophyta) are one of the most ancient multicellular lineages. Their ecological, evolutionary, and commercial importance notwithstanding, few red algal nuclear genomes have been sequenced. Our analyses of the Porphyra umbilicalis genome provide insights into how this macrophyte thrives in the stressful intertidal zone and into the basis for its nutritional value as human food. Many of the novel traits (e.g., cytoskeletal organization, calcium signaling pathways) we find encoded in the Porphyra genome are extended to other red algal genomes, and our unexpected findings offer a potential explanation for why the red algae are constrained to small stature relative to other multicellular lineages. Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection. Cytoskeletal motor proteins in Porphyra are restricted to a small set of kinesins that appear to be the only universal cytoskeletal motors within the red algae. Dynein motors are absent, and most red algae, including Porphyra, lack myosin. This surprisingly minimal cytoskeleton offers a potential explanation for why red algal cells and multicellular structures are more limited in size than in most multicellular lineages. Additional discoveries further relating to the stress tolerance of bangiophytes include ancestral enzymes for sulfation of the hydrophilic galactan-rich cell wall, evidence for mannan synthesis that originated before the divergence of green and red algae, and a high capacity for nutrient uptake. Our analyses provide a comprehensive understanding of the red algae, which are both commercially important and have played a major role in the evolution of other algal groups through secondary endosymbioses.
NOD 2 / CARD 15 variants in Malaysian patients with sporadic colorectal cancer

Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well established gene to be associated with increased susceptibility to Crohn’s disease. Thus, various studies have been performed to investigate the potential contribution of this
Relation Between the Turnover Number for Vinblastine Transport and for Vinblastine-stimulated ATP Hydrolysis by Human P-glycoprotein*

Considerable uncertainty surrounds the stoichiometry of coupling of ATP hydrolysis to drug pumping by P-glycoprotein, the multidrug transporter. To estimate relative turnovers for pumping of the drug vinblastine and ATP hydrolysis, we began by measuring the number of P-glycoprotein molecules on the surface of murine NIH3T3 cells expressing the human MDR1 gene. Fluorescence of cells treated with monoclonal antibody UIC2 was determined as a function of (i) amount of antibody at a fixed number of cells and (ii) increasing cell number at constant antibody. The two together gives 1.95 × 106 P-glycoprotein molecules/cell. Initial uptake rates of vinblastine ± verapamil measure the ability of P-glycoprotein to extract vinblastine from the plasma membrane before it enters the cell. As a function of [vinblastine] at 37 °C, they give the maximum rate of this component of outward pumping as 2.1 × 106 molecules s−1 cell−1 or a turnover number of 1.1 s−1. Initial rates of one-way efflux as a function of [vinblastine] at 25 °C ± glucose give the maximum rate of this component of pumping as 0.59 × 106 molecules s−1 cell−1. The ratio of ATPase activity of P-glycoprotein at 37 and 25 °C is 4.6. Appropriating this ratio for pumping, maximum one-way efflux at 37 °C is 4.6 × 0.59 = 2.7 × 106 molecules s−1cell−1, a turnover number of 1.4 s−1. The vinblastine-stimulated ATPase activity of P-glycoprotein has a turnover number of 3.5 s−1 at 37 °C, giving 2.8 molecules of ATP hydrolyzed for every vinblastine molecule transported in a particular direction. These calculations involve several approximations, but turnover numbers for pumping of vinblastine and for vinblastine-stimulated ATP hydrolysis are comparable. Thus, ATP hydrolysis is probably directly linked to drug transport by P-glycoprotein.
The roles of touch during phone conversations: long-distance couples' use of POKE in their homes

We report the roles of touch during phone conversations by observing long-distance couples' one month use of POKE in their homes. POKE enables users to deliver touches through an inflatable surface on the front of the device that receives index finger pressure inputs on the back of another device, while allowing the callers to maintain a conventional phone-calling posture. After a month of use by three couples, we found unexpected roles of touch in that it supported the couples in developing and sharing their tactile vocabularies by applying POKE during various conversational situations. Moreover, the findings confirmed the roles that touch play in face-to-face communication. In particular, POKE was useful for expressing and understanding emotions, resolving conversations smoothly by replacing the words, feeling close to the partner at a distance, and concentrating on the phone conversations. We conclude by discussing the unused situations, privacy issues, and usable targets to improve POKE as a way of future tactile phone conversations.
Diesel exhaust particulate (DEP) and nanoparticle exposures: What do DEP human clinical studies tell us about potential human health hazards of nanoparticles?

Engineered nanoparticles (ENPs) are increasingly tested in cellular and laboratory-animal experiments for hazard potential, but there is a lack of health effects data for humans exposed to ENPs. However, human data for another source of nanoparticle (NP) exposure are available, notably for the NPs contained in diesel exhaust particulate (DEP). Studies of human volunteers exposed to diesel exhaust (DE) in research settings report DEP-NP number concentrations (i.e., >106 particles/cm3) that exceed number concentrations reported for worst-case exposure conditions for workers manufacturing and handling ENPs. Recent human DE exposure studies, using sensitive physiological instrumentation and well-characterized exposure concentrations and durations, suggest that elevated DE exposures from pre-2007 engines may trigger short-term changes in, for example, lung and systemic inflammation, thrombogenesis, vascular function, and brain activity. Considerable uncertainty remains both as to which DE constituents underlie the observed responses (i.e., DEP NPs, DEP mass, DE gases), and as to the implications of the observed short-term changes for the development of disease. Even so, these DE human clinical data do not give evidence of a unique toxicity for NPs as compared to other small particles. Of course, physicochemical properties of toxicological relevance may differ between DEP NPs and other NPs, yet overall, the DE human clinical data do not support the idea that elevated levels of NPs per se (at least in the DEP context) must be acutely toxic by virtue of their nano-sized nature alone.
Aspects of anticoagulation in children

The number of children receiving anticoagulation is increasing. Thromboembolic events are associated with significant risk of morbidity and mortality although the optimal management of asymptomatic events remains unclear. Specific challenges in paediatrics include the diagnosis of thrombosis, delivery and monitoring of anticoagulation in a wide range of ages from neonates through to adolescents. The development of the haemostatic system as children age results in changing pathophysiology of thrombosis and response to anticoagulation agents. Although registry and observational studies have provided vital information, specific paediatric, prospective anticoagulation studies have been few and limited in design. The result is that much of current practice is extrapolated from adult studies. Traditional anticoagulants have significant limitations. Both heparin and warfarin are in widespread use but many fundamental questions regarding dose, therapeutic range, efficacy and optimum duration have not been fully answered. Alternative agents, such as direct thrombin inhibitors and the selective anti‐factor Xa inhibitor fondaparinux, may have advantages for children. Clinical trials in adults and preliminary data in children are promising but caution should be applied until specific paediatric studies have demonstrated safety and efficacy.
Assessing aspirin responsiveness in subjects with multiple risk factors for vascular disease with a rapid platelet function analyzer

Aspirin, compared with placebo, reduces the risk of cardiovascular events by 25% in populations of patients with and without known arterial vascular disease. However, the phenomena of ‘aspirin resistance’ that has been described in 5–50% of this population may critically reduce aspirin's efficacy. One study has suggested that aspirin-resistant patients have a 3.5 times higher risk of cardiovascular death. Presently, there are no established, simple, broadly used methods determining antiplatelet properties of aspirin, while conventional aggregometry requires special equipment and trained personnel. We sought to determine the validity of an Ultegra analyzer with the novel aspirin-sensitive cartridge before and after one pill of non-enteric coated aspirin (325 mg) in subjects with multiple risk factors for coronary artery disease. One hundred and fifty-four volunteers were enrolled into the multicenter study, but six of them were excluded. Data from 148 participants were analyzed. Platelets were assessed twice at baseline (pre-aspirin), and after 2–30 h (post-aspirin). We employed 5 μmol/l epinephrine-induced conventional aggregometry, and aspirin response units stimulated by propyl gallate with the point-of-care Ultegra analyzer. A single pill of aspirin reduced platelet-rich plasma aggregation from 72 ± 21% to 25 ± 10%, and diminished aspirin reduction units from 647 ± 95 to 436 ± 69. The overall agreement between the two methods was 87% with 85% sensitivity for Ultegra and 88% for platelet aggregation, respectively. The correlation between the two methods was 0.902. Timely determination of aspirin resistance represents an indispensable application in current medicine. The Ultegra RPFA-ASA analyzer is a novel, fast method that could be used in clinical practice for monitoring efficacy of aspirin, and for triaging the aspirin-resistant population. The clinical implications of these data need to be proven in randomized trials.
The Internationalization Theory and Malaysian Small Medium Enterprises (SMEs)

Reduction in trade barriers and development in information and communication technology provide the opportunity for small and medium enterprises (SMEs) to expand their business into foreign market, even on the first day of its establishment. Such circumstances have lead into a debate among internationalization researchers on which theory effectively explain the firm's internationalization process and whether the older theories are not relevant anymore these days. Therefore, the objective of this paper is to look at the internationalization process of Malaysian SMEs and how it fits the internationalization theories. Discussions are based on the related theories of internationalization namely the Uppsala Model, Network Approach and International New Venture or Born global. This paper also presents a descriptive analysis on the level of internationalization among Malaysian SMEs, reason for internationalization, the mode of entry used, and the reason for non-internationalization among firms that have no international activities. Data were collected through self-administered questionnaire and a total of 250 responds were received. Findings indicate that all three theories are still applicable as not all SMEs that internationalized are born global in nature. Exporting was the most used mode of entry and increasing profit was the main reason for internationalization. Potential difficulties and uncertainties in making profit appear to be the major reason for non-internationalization. Discussions of the findings, significance of the study and direction for future research are then discussed.
Spectroscopic Constraints on Models of Ion Cyclotron Resonance Heating in the Polar Solar Corona and High-Speed Solar Wind

Using empirical ion velocity distributions derived from Ultraviolet Coronagraph Spectrometer (UVCS) and Solar Ultraviolet Measurements of Emitted Radiation (SUMER) ultraviolet spectroscopy, we construct theoretical models of the nonequilibrium plasma state of the polar solar corona. The primary energy deposition mechanism we investigate is the dissipation of high-frequency (10-10,000 Hz) ion cyclotron resonant Alfvén waves which can heat and accelerate ions differently depending on their charge and mass. We solve the internal energy conservation equations for the ion temperature components parallel and perpendicular to the superradially expanding magnetic field lines and use empirical constraints for the remaining parameters. We find that it is possible to explain many of the kinetic properties of the plasma (such as high perpendicular ion temperatures and strong temperature anisotropies) with relatively small amplitudes for the resonant waves. There is suggestive evidence for steepening of the Alfvén wave spectrum between the coronal base and the largest heights observed spectroscopically, and it is important to take Coulomb collisions into account to understand observations at the lowest heights. Because the ion cyclotron wave dissipation is rapid, the extended heating seems to demand a constantly replenished population of waves over several solar radii. This indicates that the waves are generated gradually throughout the wind rather than propagated up from the base of the corona.
Bacteria of Dental Caries in Primary and Permanent Teeth in Children and Young Adults

ABSTRACT Although Streptococcus mutans has been implicated as a major etiological agent of dental caries, our cross-sectional preliminary study indicated that 10% of subjects with rampant caries in permanent teeth do not have detectable levels of S. mutans. Our aims were to use molecular methods to detect all bacterial species associated with caries in primary and permanent teeth and to determine the bacterial profiles associated with different disease states. Plaque was collected from 39 healthy controls and from intact enamel and white-spot lesions, dentin lesions, and deep-dentin lesions in each of 51 subjects with severe caries. 16S rRNA genes were PCR amplified, cloned, and sequenced to determine species identities. In a reverse-capture checkerboard assay, 243 samples were analyzed for 110 prevalent bacterial species. A sequencing analysis of 1,285 16S rRNA clones detected 197 bacterial species/phylotypes, of which 50% were not cultivable. Twenty-two new phylotypes were identified. PROC MIXED tests revealed health- and disease-associated species. In subjects with S. mutans, additional species, e.g., species of the genera Atopobium, Propionibacterium, and Lactobacillus, were present at significantly higher levels than those of S. mutans. Lactobacillus spp. , Bifidobacterium dentium, and low-pH non-S. mutans streptococci were predominant in subjects with no detectable S. mutans. Actinomyces spp. and non-S. mutans streptococci were predominant in white-spot lesions, while known acid producers were found at their highest levels later in disease. Bacterial profiles change with disease states and differ between primary and secondary dentitions. Bacterial species other than S. mutans, e.g., species of the genera Veillonella, Lactobacillus, Bifidobacterium, and Propionibacterium, low-pH non-S. mutans streptococci, Actinomyces spp. , and Atopobium spp. , likely play important roles in caries progression.
A Probabilistic Estimation Bias Circuit for Fixed-Width Booth Multiplier and Its DCT Applications

In this brief, a probabilistic estimation bias (PEB) circuit for a fixed-width two's-complement Booth multiplier is proposed. The proposed PEB circuit is derived from theoretical computation, instead of exhaustive simulations and heuristic compensation strategies that tend to introduce curve-fitting errors and exponential-grown simulation time. Consequently, the proposed PEB circuit provides a smaller area and a lower truncation error compared with existing works. Implemented in an 8 × 8 2-D discrete cosine transform (DCT) core, the DCT core using the proposed PEB Booth multiplier improves the peak signal-to-noise ratio by 17 dB with only a 2% area penalty compared with the direct-truncated method.
Potent Trypanocidal Curcumin Analogs Bearing a Monoenone Linker Motif Act on Trypanosoma brucei by Forming an Adduct with Trypanothione

We have previously reported that curcumin analogs with a C7 linker bearing a C4-C5 olefinic linker with a single keto group at C3 (enone linker) display midnanomolar activity against the bloodstream form of Trypanosoma brucei. However, no clear indication of their mechanism of action or superior antiparasitic activity relative to analogs with the original di-ketone curcumin linker was apparent. To further investigate their utility as antiparasitic agents, we compare the cellular effects of curcumin and the enone linker lead compound 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (AS-HK014) here. An AS-HK014–resitant line, trypanosomes adapted to AS-HK014 (TA014), was developed by in vitro exposure to the drug. Metabolomic analysis revealed that exposure to AS-HK014, but not curcumin, rapidly depleted glutathione and trypanothione in the wild-type line, although almost all other metabolites were unchanged relative to control. In TA014 cells, thiol levels were similar to untreated wild-type cells and not significantly depleted by AS-HK014. Adducts of AS-HK014 with both glutathione and trypanothione were identified in AS-HK014–exposed wild-type cells and reproduced by chemical reaction. However, adduct accumulation in sensitive cells was much lower than in resistant cells. TA014 cells did not exhibit any changes in sequence or protein levels of glutathione synthetase and γ-glutamylcysteine synthetase relative to wild-type cells. We conclude that monoenone curcuminoids have a different mode of action than curcumin, rapidly and specifically depleting thiol levels in trypanosomes by forming an adduct. This adduct may ultimately be responsible for the highly potent trypanocidal and antiparasitic activity of the monoenone curcuminoids.
Performance Improvement of $\hbox{Sm}_{2}\hbox{O}_{3}$  MIM Capacitors by Using Plasma Treatment After Dielectric Formation

In this letter, we investigate the dependence of the performance of metal-insulator-metal (MIM) capacitors with Sm<sub>2</sub>O<sub>3</sub> dielectric on plasma treatment (PT) performed before Sm<sub>2</sub>O<sub>3</sub> deposition, after Sm<sub>2</sub>O<sub>3</sub> deposition, or both before and after Sm<sub>2</sub>O<sub>3</sub> deposition. By performing PT in N<sub>2</sub> ambient (PTN) after Sm<sub>2</sub>O<sub>3</sub> dielectric formation, the effective quadratic voltage coefficient of capacitance (VCC) can be reduced from 498 to 234 ppm/V<sup>2</sup> and the effective linear VCC can be reduced from 742.3 to 172 ppm/V for MIM capacitor with Sm<sub>2</sub>O<sub>3</sub> dielectric having a capacitance density of ~ 7.5 fF/mum<sup>2</sup>. The leakage current density at +3.3 V can be reduced from 3.44 10<sup>-7</sup> to 1.60 times 10<sup>-8</sup> A/cm<sup>2</sup> by performing PTN in both before and after Sm<sub>2</sub>O<sub>3</sub> deposition. PTN after dielectric formation is an effective way to improve the performance of high-kappa dielectric MIM capacitors for RF and analog/mixed signal IC applications.