Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro transport of gimatecan (7-t-butoxyiminomethylcamptothecin) by breast cancer resistance protein, P-glycoprotein, and multidrug resistance protein 2

Lipophilic camptothecin derivatives are considered to have negligible affinity for breast cancer resistance protein (BCRP; ABCG2). Gimatecan, a new orally available 7-t-butoxyiminomethyl–substituted lipophilic camptothecin derivative, has been previously reported to be not a substrate for BCRP. Using a panel of in vitro models, we tested whether gimatecan is a substrate for BCRP as well as for P-glycoprotein (MDR1) or multidrug resistance protein 2 (MRP2; ABCC2), ATP-binding cassette drug efflux transporters involved in anticancer drug resistance, and able to affect the pharmacokinetics of substrate drugs. Cell survival, drug transport, accumulation, and efflux were studied in IGROV1 and (human BCRP overexpressing) T8 cells, Madin-Darby canine kidney II (MDCKII-WT, MDCKII-Bcrp1, MDCKII-MDR1, and MDCKII-MRP2), and LLCPK (LLCPK-WT and LLCPK-MDR1) cells. Competition with methotrexate uptake was studied in Sf9-BCRP membrane vesicles. In vitro, expression of BCRP resulted in 8- to 10-fold resistance to gimatecan. In Transwell experiments, gimatecan was transported by Bcrp1 and transport was inhibited by the BCRP/P-glycoprotein inhibitors elacridar and pantoprazole. Efflux of gimatecan from MDCKII-Bcrp1 cells was faster than in WT cells. In Sf9-BCRP membrane vesicles, gimatecan significantly inhibited BCRP-mediated transport of methotrexate. In contrast, gimatecan was not transported by MDR1 or MRP2. Gimatecan is transported by BCRP/Bcrp1 in vitro, although to a lesser extent than the camptothecin analogue topotecan. Implications of BCRP expression in the gut for the oral development of gimatecan and the interaction between gimatecan and other BCRP substrate drugs and/or inhibitors warrant further clinical investigation. [Mol Cancer Ther 2007;6(12):3307–13]
Clinical features, molecular diagnosis, and treatment outcome of infants with leukemia in Taiwan

Infant leukemia is rare and quite distinct from other childhood leukemias. Differentiating between leukemia and transient myeloproliferative disorder (TMD) in phenotypically normal infants is sometimes difficult. The clinical features and molecular analyses for the fusion transcripts of mixed lineage leukemia (MLL) gene rearrangement in infant leukemia have not been well documented in the Chinese population.
All mutually unbiased bases in dimensions two to five

All complex Hadamard matrices in dimensions two to five are known. We use this fact toderive all inequivalent sets of mutually unbiased (MU) bases in low dimensions. We finda three-parameter family of triples of MU bases in dimension four and two inequivalentclasses of MU triples in dimension five. We confirm that the complete sets of (d + 1)MU bases are unique (up to equivalence) in dimensions below six, using only elementaryarguments for d less than five.
Communication, Renegotiation, and the Scope for Collusion

We use experiments to analyze what type of communication is most effective in achieving cooperation in a simple collusion game. Consistent with the existing literature on communication and collusion, even minimal communication leads to a short run increase in collusion. However, in a limited message-space treatment where subjects cannot communicate contingent strategies, this initial burst of collusion rapidly collapses. When unlimited pre-game communication is allowed via a chat window, an initial decline in collusion is reversed over time. Content analysis is used to identify multiple channels by which communication improves collusion in this setting. Explicit threats to punish cheating prove to be by far the most important factor to successfully establish collusion, consistent with the existing theory of collusion. However, collusion is even more likely when we allow for renegotiation, contrary to standard theories of renegotiation. What appears critical for the success of collusion with renegotiation is that cheaters are often admonished in strong terms. Allowing renegotiation therefore appears to increase collusion by allowing for an inexpensive and highly effective form of punishment.
The relationships among aboveground biomass, primary productivity, precipitation and temperature in grazed and ungrazed temperate grasslands from northern Turkey

In this study, it is evaluated the relationship between in climate and variability in above-ground net primary production (ANPP), above-ground live biomass (AGLB) and peak above-ground live biomass (PAGLB) in grazed and ungrazed temperate grasslands from northern Turkey. Rain use efficiency (RUE) is averagely estimated as 0.51±0.11 and 0.85±0.20 gDM.m-². mm-¹. yr-¹ in grazed and ungrazed stand of the study area respectively. The monthly and annual precipitation indicate to have linear relationship with ANPP and PAGLB according to the regression analysis in ungrazed and grazed stands of study area. RUE of ungrazed stand was generally higher than grazing stand.
Integrated Flight Scheduling and Fleet Assignment Under Airport Congestion

Airport congestion is a major cause for the large delays that currently affect the air transport industry. These delays have huge cost implications---for the U.S. economy these costs were estimated at $32.9 billion in 2007. In this paper, we present a mixed-integer linear optimization model aimed at assisting airlines in the making of integrated flight scheduling and fleet assignment decisions that take aircraft and passenger delay costs explicitly into account. The objective of the model is to maximize the expected profits of an airline that faces a given origin/destination-based travel demand and operates in congested, slot-constrained airports. Both airline competition and airline cooperation are dealt with in the model, though in a simplified manner. The model was applied to a case study involving the main network of TAP Portugal, which comprises 31 airports and 100 daily flight legs. The results obtained through the model suggest that the Portuguese legacy carrier can improve their expected profits significantly, while diminishing the total number of flights and slightly increasing the passengers' average connecting time. The calculation effort involved in the application of the model even on a desktop computer is small enough to allow its real-time utilization in International Air Transport Association scheduling conferences. These findings clearly indicate that the model is a significant addition to the airline planning toolbox.
Use of Upper-Arm Anthropometry as Measure of Body-Composition and Nutritional Assessment in Children and Adolescents (6–20 Years) of Assam, Northeast India

Background Upper-arm muscle area (UMA), upper-arm fat area (UFA), arm-fat index (AFI), upper-arm fat estimate (UFE) and upper-arm muscle estimate (UME) was introduced for the assessment of body-composition. This cross-sectional study assessed age-sex specific upper-arm composition and nutritional status among children and adolescents. Methods The present cross-sectional study was conducted among 1545 (770 boys; 775 girls) Sonowal Kacharis of Dibrugarh District, Assam, Northeast-India, using multi-stage stratified random sampling method. The anthropometric measurements of height, weight, triceps and mid-upper-arm circumference were recorded. The upper-arm composition was assessed using standard equations. Nutritional status was assessed using standard classification of upper-arm muscle-area by height (UAMAH) and thinness (low BMI-for-age). Results Age and sex-specific muscularity were found significantly greater among boys than girls (p<0.01), while adiposity was significantly greater among girls (p<0.01), particularly when they approached to puberty. The overall prevalence of low and below-average UAMAH was found to be 16.38% and 22.65% respectively. The overall prevalence of thinness was 23.69% (26.36% boys, 21.03% girls) (p>0.05). Conclusion Body-composition and nutritional status of these children and adolescents were found markedly unsatisfactory using upper-arm composition, UAMAH and thinness. The combination of upper-arm composition and conventional anthropometric measures appear to be useful for body-composition and nutritional status assessment.
Renal function markers and thyroid hormone status in undialyzed chronic kidney disease

Objective: The study was undertaken to quantify thyroid hormones in undialyzed chronic kidney disease patients' verses controls and to study the correlation between renal function markers and thyroid hormones. Background: Chronic kidney disease (CKD) is associated with a higher prevalence of primary hypothyroidism (HT), but at the same studies on thyroid hormone status in uremic patients has reported conflicting results. Methods: Thyroid hormones and renal function parameters like serum urea, creatinine, creatinine clearance, total protein and albumin were estimated and correlations between thyroid hormones and renal function parameters were studied in 60 undialyzed chronic kidney disease patients' verses 100 healthy controls. Results: We found both T3 and T4 were significantly reduced (p<0.0001 for T3 and 0.007 for T4) whereas TSH remains to be unchanged in patient group compared to controls. We also observed that urea and creatinine were negatively correlated whereas creatinine clearance was positively correlated with both T3 and T4 that has high statistical (two-tailed) significance at 0.01 level. But urea alone is negatively correlated with TSH that has statistical (two-tailed) significance at 0.05 level. Conclusion: From our data, we speculate that renal insufficiency may lead to thyroid hormone disturbances.
“Right on all Occasions?” – On the Feasibility of Laterality Research Using a Smartphone Dichotic Listening Application

Most psychological experimentation takes place in laboratories aiming to maximize experimental control; however, this creates artificial environments that are not representative of real-life situations. Since cognitive processes usually take place in noisy environments, they should also be tested in these contexts. The recent advent of smartphone technology provides an ideal medium for such testing. In order to examine the feasibility of mobile devices (MD) in psychological research in general, and laterality research in particular, we developed a MD version of the widely used speech laterality test, the consonant-vowel dichotic listening (DL) paradigm, for use with iPhones/iPods. First, we evaluated the retest reliability and concurrent validity of the DL paradigm in its MD version in two samples tested in controlled, laboratory settings (Experiment 1). Second, we explored its ecological validity by collecting data from the general population by means of a free release of the MD version (iDichotic) to the iTunes App Store (Experiment 2). The results of Experiment 1 indicated high reliability (rICC = 0.78) and validity (rICC = 0.76–0.82) of the MD version, which consistently showed the expected right ear advantage (REA). When tested in real-life settings (Experiment 2), participants (N = 167) also showed a significant REA. Importantly, the size of the REA was not dependent on whether the participants chose to listen to the syllables in their native language or not. Together, these results establish the current MD version as a valid and reliable method for administering the DL paradigm both in experimentally controlled as well as uncontrolled settings. Furthermore, the present findings support the feasibility of using smartphones in conducting large-scale field experiments.
Source Coding and Transmission of HDTV Images Compressed with the Wavelet Transform

Digital high-definition TV (HDTV) signals are generally compressed to reduce transmission bandwidth requirements. A compression algorithm for the bit rate reduction of an HDTV image using the wavelet transform is presented. The major problems related to the transmission of a compressed HDTV signal are analyzed. Transmission is examined both on a noisy channel and an asynchronous transfer mode (ATM) network. The effects of channel noise on the reconstructed image are determined, and a solution to mitigate the degradation of the image quality is presented. A model for the output bit rate of the HDTV coder is derived and used to simulate the transmission of an ATM multiplexer so that the network's main performance parameters can be determined. >
Modeling the effect of copper availability on bacterial denitrification

When denitrifying bacteria such as Paracoccus denitrificans respire anaerobically they convert nitrate to dinitrogen gas via a pathway which includes the potent greenhouse gas, nitrous oxide (N2O). The copper‐dependent enzyme Nitrous Oxide reductase (Nos) catalyzes the reduction of N2O to dinitrogen. In low‐copper conditions, recent experiments in chemostats have demonstrated that Nos efficiency decreases resulting in significant N2O emissions. For the first time, a chemostat‐based mathematical model is developed that describes the anaerobic denitrification pathway based on Michaelis–Menten kinetics and published kinetic parameters. The model predicts steady‐state enzyme levels from experimental data. For low copper concentrations, the predicted Nos level is significantly reduced, whereas the levels for the non copper‐dependent reductases in the pathway remain relatively unaffected. The model provides time courses for the pathway metabolites that accurately reflect previously published experimental data. In the absence of experimental data purely predictive analyses can also be readily performed by calculating the relative Nos level directly from the copper concentration. Here, the model quantitatively estimates the increasing level of emitted N2O as the copper level decreases.
Neutrophil Clearance: when the party’s over, cleanup begins

Maintenance of circulating, functional neutrophils and their robust recruitment to tissues in response to injury and/or microbial infection are critical for host defense. Equally important, though less well understood, are the processes for removal of these short-lived cells. Here we review recent findings of novel neutrophil characteristics that determine removal. These neutrophil-derived signals, in turn, can shape the responses of other cells and surrounding tissues and promote a return to homeostasis. If not removed, dying neutrophils disintegrate and release phlogistic cargo that can further contribute to ongoing inflammation, tissue destruction, or autoimmunity.
Correlation between curve severity, somatosensory evoked potentials, and magnetic resonance imaging in adolescent idiopathic scoliosis.

STUDY DESIGN A prospective study in patients with adolescent idiopathic scoliosis of different clinical severity using whole-spine magnetic resonance imaging and somatosensory evoked potentials. OBJECTIVES To correlate the presence of magnetic resonance imaging structural abnormalities with somatosensory evoked potential-detected functional disorders in the hind brain and spinal cord and the Cobb's angle in patients with adolescent idiopathic scoliosis and to compare the result with those in healthy matched control subjects. SUMMARY OF BACKGROUND DATA Many different types of neurologic dysfunction have been reported in scoliosis. With the advent of magnetic resonance imaging, there are increased reports on the association of idiopathic scoliosis and syringomyelia, Chiari I malformation, or tonsillar ectopia. The actual link between structural and functional disorder in idiopathic scoliosis is, however, unclear. METHODS Posterior tibial nerve evoked potentials and whole-spine magnetic resonance imaging were performed in 36 healthy control subjects, 135 patients with adolescent idiopathic scoliosis with Cobb's angle less than 45 degrees, and 29 patients with Cobb's angle more than 45 degrees. RESULTS Tonsillar ectopia or syringomyelia, detected by magnetic resonance imaging, or functional disturbance in the somatosensory pathway, detected by somatosensory evoked potentials, was found to be significantly more frequent in the group of patients with severe scoliosis curvature, with an incidence of 31% and 27.6%, respectively. Incidence of tonsillar ectopia was 33.3% in patients with abnormal somatosensory evoked potentials in contrast to the much lower incidence of 2.9% in patients with normal somatosensory evoked potentials. There was a significant structural and functional link. The incidence of syringomyelia in patients with and without tonsillar ectopia was 33.3% and 0.7%, respectively. CONCLUSIONS In patients with adolescent idiopathic scoliosis with severe curve, the significant association with tonsillar ectopia and abnormal somatosensory function points to a neural origin. Disorders in the somatosensory function may be one of the mechanisms linking tonsillar ectopia to scoliosis. Somatosensory evoked potentials and magnetic resonance imaging may have important diagnostic and predictive value and may help in the management of adolescent idiopathic scoliosis.
Reduced folate carrier: tissue distribution and effects of chronic ethanol intake in the micropig.

BACKGROUND Folate deficiency is common in alcoholic patients, in part due to abnormal transport across membranes relevant to folate homeostasis. The reduced folate carrier (RFC) transports monoglutamyl folates across tissue membranes and could be affected by chronic exposure to ethanol. The micropig model is suitable to study the effect of alcoholism on RFC and folate transport across membranes. METHODS The membrane transport of [3H]-folic acid was measured by a vacuum filtration method in jejunal brush border (JBB), liver plasma membrane (LPM), and kidney brush border (KBB) membranes vesicles from micropigs fed control or 40% ethanol diets for 12 months. RFC transcripts were analyzed by reverse transcription polymerase chain reaction in jejunal mucosa, liver, and kidney from the same animals. RESULTS When we compared results from three relevant membranes in control animals, the transport of [3H]-folic acid was highest in LPM, 3-fold lower in KBB (p < 0.001), and 6-fold lower in JBB (p < 0.001). The concentration of RFC transcripts per total RNA was greatest in liver, followed by kidney and jejunum. The transport of [3H]-folic acid by JBB vesicles from chronic ethanol-fed animals exhibited 2-fold lower Km and Vmax (p < 0.05), whereas there was no ethanol effect on the Vmax of [3H]-folic acid transport by LPM or KBB. RFC transcript levels were 10-fold lower in jejunal mucosa from ethanol-fed animals than in control-fed animals (p < 0.005). CONCLUSIONS Although our findings demonstrate different RFC transcript amounts and transport efficiencies among tissues, the present studies suggest that chronic ethanol exposure decreases the intestinal absorption of folic acid by altering the expression of RFC and consequently its transport kinetics in JBB. These findings provide a mechanism for the clinical finding of reduced folic acid absorption in chronic alcoholics.
Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis

The PI-3 kinase (PI-3K)/mTOR pathway is critical for cell growth and proliferation. Strategies of antagonising this signaling have proven to be detrimental to cell survival. This observation, coupled with the fact many tumours show enhanced growth signaling, has caused dual inhibitors of PI-3K and mTOR to be implicated in cancer treatment, and have thus been studied across various tumour models. Since PI-3K (class-I)/mTOR pathway negatively regulates autophagy, dual inhibitors of PI-3K/mTOR are currently believed to be autophagy activators. However, our present data show that the dual PI-3K/mTOR inhibition (DKI) potently suppresses autophagic flux. We further confirm that inhibition of Vps34/PI3KC3, the class-III PI-3K, causes the blockade to autophagosome-lysosome fusion. Our data suggest that DKI induces cell death independently of apoptosis and necroptosis, whereas autophagy perturbation by DKI may contribute to cell death. Given that autophagy is critical in cellular homeostasis, our study not only clarifies the role of a dual PI-3K/mTOR inhibitor in autophagy, but also suggests that its autophagy inhibition needs to be considered if such an agent is used in cancer chemotherapy.
Chiral phase transitions in strong chromomagnetic fields at finite temperature and dimensional reduction

Dynamical fermion mass generation in external chromomagnetic fields is considered at non--zero temperature. The general features of dynamical chiral symmetry breaking ($D\chi SB$) are investigated for several field configurations in relation to their symmetry properties and the form of the quark spectrum. According to the fields, there arises dimensional reduction by one or two units. In all cases there exists $D\chi SB$ even at weak quark attraction, confirming the idea about the dimensional insensitivity of this mechanism in a chromomagnetic field.
Response dynamics and receptive-field organization of catfish ganglion cells [published erratum appears in J Gen Physiol 1995 Aug;106(2):following 388]

Responses from catfish retinal ganglion cells were evoked by a spot or an annulus of light and were analyzed by a procedure identical to the one used previously to study catfish amacrine cells (Sakai H. M., and K.-I. Naka, 1992. Journal of Neurophysiology. 67:430-442.). In two- input white-noise experiments, a response evoked by simultaneous stimulation of the center and surround was decomposed into the components generated by the center and surround through a process of cross-correlation. The center and surround responses were also decomposed into their linear and nonlinear components so that the response dynamics of the linear and nonlinear components could be measured. We found that the concentric organization of the receptive field was determined by linear components, i.e., the first-order kernels generated by the center and surround were of opposite polarity. Both the center and surround generated second-order kernels with similar signatures, i.e., the second-order components formed a monotonic receptive field. The peak response time of the first- and second-order kernels from the surround was longer by approximately 20 ms than that of the center. Except for the DC potential present in the intracellular responses, almost identical first- and second-order kernels for the center and surround were obtained from both the intracellular response and spike discharges. Thus, information on concentric organization of a receptive field is translated into spike discharges with little loss of information. A train of spike discharges carries, simultaneously, at least four kinds of information: two linear and two nonlinear components, which originate in the receptive field center and the surround. A spike train is not a simple signaling device but is a carrier of complex and multiple signals. Victor, J. D. , and R. M. Shapley (1979. Journal of General Physiology. 74:671-687.) discovered similarly that, in the cat retina, static second-order nonlinearity is encoded into spike trains. Results obtained in this study support the thesis that signals generated by the preganglionic cells are translated into spike discharges without major modification and that those signals can be recovered from the spike trains (Sakuranaga, M., Y. Ando, and K.-I. Naka. 1987. Journal of General Physiology. 90:229-259.; Korenberg, M. J., H. M. Sakai, and K.-I. Naka. 1989. Journal of Neurophysiology. 61:1110-1120.). Current injection studies have shown that such signal transmission is possible (Sakai, H. M., and K.-I. Naka, 1988a. Journal of Neurophysiology. 60:1549-1567.; 1990. Journal of Neurophysiology. 63:105-119.).