Miracle-dz/UniFAR-FTUs huggingface dataset:
Dok-R Mediates Attenuation of Epidermal Growth Factor-Dependent Mitogen-Activated Protein Kinase and Akt Activation through Processive Recruitment of c-Src and Csk

ABSTRACT Dok-R has previously been shown to associate with the epidermal growth factor receptor (EGFR) and become tyrosine phosphorylated in response to EGF stimulation. The recruitment of Dok-R to the EGFR, which is mediated through its phosphotyrosine binding (PTB) domain, results in attenuation of mitogen-activated protein kinase (MAPK) activation. Dok-R's ability to attenuate EGF-driven MAPK activation is independent of its ability to recruit rasGAP, a known attenuator of MAPK activity, suggesting an alternate Dok-R-mediated pathway. Herein, we have determined the structural determinants within Dok-R that are required for its ability to attenuate EGF signaling and to associate with c-Src and with the Src family kinase (SFK)-inhibitory kinase, Csk. We demonstrate that Dok-R associates constitutively with c-Src through an SH3-dependent interaction and that this association is essential to Dok-R's ability to attenuate c-Src activity and diminish MAPK and Akt/PKB activity. We further illustrate that EGF-dependent phosphorylation of Dok-R requires SFK activity and, more specifically, that SFK-dependent phosphorylation of tyrosine 402 on Dok-R facilitates the inducible recruitment of Csk. We propose that recruitment of Csk to Dok-R serves to bring Csk to c-Src and down-regulate its activity, resulting in a concomitant attenuation of MAPK and Akt/PKB activity. Furthermore, we demonstrate that Dok-R can abrogate c-Src's ability to protect the breast cancer cell line SKBR3 from anoikis and that an association with c-Src and Csk is required for this activity. Collectively these results demonstrate that Dok-R acts as an EGFR-recruited scaffolding molecule that processively assembles c-Src and Csk to attenuate signaling from the EGFR.
Conserved and nonconserved features of the folding pathway of hisactophilin, a β‐trefoil protein

Based on previous studies of interleukin‐1β (IL‐1β) and both acidic and basic fibroblast growth factors (FGFs), it has been suggested that the folding of β‐trefoil proteins is intrinsically slow and may occur via the formation of essential intermediates. Using optical and NMR‐detected quenched‐flow hydrogen/deuterium exchange methods, we have measured the folding kinetics of hisactophilin, another β‐trefoil protein that has <10% sequence identity and unrelated function to IL‐1β and FGFs. We find that hisactophilin can fold rapidly and with apparently two‐state kinetics, except under the most stabilizing conditions investigated where there is evidence for formation of a folding intermediate. The hisactophilin intermediate has significant structural similarities to the IL‐1β intermediate that has been observed experimentally and predicted theoretically using a simple, topology‐based folding model; however, it appears to be different from the folding intermediate observed experimentally for acidic FGF. For hisactophilin and acidic FGF, intermediates are much less prominent during folding than for IL‐1β. Considering the structures of the different β‐trefoil proteins, it appears that differences in nonconserved loops and hydrophobic interactions may play an important role in differential stabilization of the intermediates for these proteins.
Serum IFN-γ-inducible chemokines CXCL9 and CXCL10 are elevated in non-immediate drug hypersensitivity reactions.

BACKGROUND The recruitment to the skin of drug-responsive T cells is responsible for the inflammatory profiles of non-immediate drug hypersensitivity reactions (niDHRs). Maculopapular exanthema (MPE) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have quite distinct T cell infiltrating patterns. OBJECTIVE To investigate serum levels of CXCL9, CXCL10 and IFN-γ in patients with niDHRs, including MPE and SJS/TEN, to evaluate correlations between the cytokines, and to determine whether the inflammatory factors correlate with clinical severity in patients with SJS/TEN. METHOD Twenty-four patients with SJS/TEN, 24 patients with MPE, and 24 healthy donors with good tolerance to the drugs involved in the drug reactions were recruited into the study. The modified severity-of-illness score for TEN (SCORTEN) and detachment of body surface area (dBSA) were used to assess the clinical severity of SJS/TEN. Serum levels of CXCL9, CXCL10 and IFN-? were determined by ELISA. RESULTS The niDHRs group, SJS/TEN and MPE subgroups all exhibited significantly higher levels of CXCL9, CXCL10 and IFN-γ compared with the control group (P < 0.001). Serum IFN-γ levels were positively correlated with CXCL9 levels and CXCL10 levels in patients with niDHRs (rs = 0.576, rs = 0.449, P < 0.05). None of the levels of CXCL9, CXCL10 and IFN-γ had any correlation with modified SCOTEN index or dBSA in SJS/TEN group. CONCLUSIONS The results suggest Th1 cytokine IFN-γ and chemokines CXCL9 and CXCL10 may play roles in the pathogenesis of niDHRs.
The influence of exclusion criteria on the relationship between suicide rates and age in cross-national studies

Traditionally, suicide rates increase with aging in many countries (Shah and De, 1998). However, exceptions to this observation are emerging. Data from the World Health Organization (WHO) in 1995 revealed that female suicide rates did not increase with age in Mauritius, Colombia, Albania and Finland (Shah and De, 1998). Suicide rates increased with age in Switzerland (Ajdacic-Gross et al., 2006), Brazil (Mello-Santos et al., 2005) and China (Yip et al., 2000), but there were smaller peaks in the younger age-bands. Suicide rates among Australian, New Zealand and white American males increased with age, but suicide rates for females initially increased with age, peaking at menopause, and declining thereafter (Skegg and Cox, 1991; Woodbury et al., 1988; Snowdon and Snowdon, 1995). Suicide rates among non-white Americans (Seiden, 1981; Woodbury et al., 1988), Indians (Adityanjee, 1986; Bhatia et al., 1987), Jordanians (Daradekh, 1989), Indian immigrants to the U.K. (Raleigh et al., 1990; Needleman et al., 1997) and some east European countries (Sartorius, 1995) declined with increasing age.
Power Isn’t Everything: Muscle Function and Energetic Costs during Steady Swimming in Atlantic Cod (Gadus morhua)

Power produced by red myotomal muscles of fish during cruise swimming appears seldom maximized, so we sought to investigate whether economy may impact or dominate muscle function. We measured cost of transport (COT) using oxygen consumption and the strain trajectories and electromyographic activity of red muscle measured at anterior (ANT) and posterior (POST) locations while Atlantic cod (Gadus morhua) swam steadily at speeds between 0.3 and 1.0 body lengths (BL) s−1. We then measured the power produced by isolated segments of red muscle when activated either as in the swimming cod or such that maximal net power was produced. Patterns of activation during swimming were not optimal for power output and were highly variable between tail beats, particularly at the ANT location and at slow swim speeds. Muscle strain amplitude did not increase until swimming speed reached 0.9 (ANT) versus 0.5 (POST) BL s−1. These limited power to only 53% (ANT) and 71% (POST) of maximum at slower swim speeds and to 70%–80% of maximum at high swim speeds. COT (resting metabolism subtracted) was minimal at the slowest swim speed, surprisingly, where power was most impaired by activation and strain. Thus, production of powered forces for maneuverability/stability appeared to greatly impact red muscle function during cruise swimming in cod, particularly at slow speeds and in ANT muscle.
Strawberry Growth and Development in an Annual Plasticulture System

The growth and development of three strawberry cultivars commonly grown in a plasticulture system were documented. Strawberry plants were harvested monthly and divided by roots, crown, leaves, flowers, and fruit and then dried in an oven. The dry matter production and resource allocation proceeded along a predictable pattern of development. The establishment phase was characterized by an active period of growth of root, crown and leaves in the fall. Through the winter, the plants underwent slow growth, ending in a transition period in the late winter/early spring when resources were allocated to both vegetative and reproductive growth. In the spring, all plant parts received significantly increased allocation of, or redistribution of, resources. Cultivars of California origin, 'Chandler' and 'Camarosa', displayed similar trends in yield, dry matter production, seasonal resource allocation, and growth analysis variables throughout the season. 'Sweet Charlie', a cultivar from Florida, showed lower dry matter accumulation and relative growth rate in the spring, higher harvest index and lower yield than the California cultivars.
Generation of free radicals from model lipid hydroperoxides and H2O2 by Co(II) in the presence of cysteinyl and histidyl chelators.

Electron spin resonance spin trapping was utilized to investigate the generation of free radicals from cumene hydroperoxide (cumene-OOH), tert-butyl hydroperoxide (tert-butyl-OOH), and H2O2 at pH 7.2 by Co(II) in the presence of cysteinyl and histidyl chelating agents. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide. Incubation of Co(II) with cumene-OOH or tert-butyl-OOH did not generate any detectable amounts of free radicals. However, in the presence of glutathione, cysteine, penicillamine, or N-acetylcysteine, Co(II) generated cumene-OOH-derived carbon-centered radicals, cumene alkoxyl radicals, and hydroxyl (.OH) radicals. Oxidized glutathione and cystine used instead of reduced glutathione or cysteine did not generate any free radical, indicating an important role of the -SH group in radical generation. While the addition of diethylenetriaminepentaacetic acid (DTPA) prevented radical generation, deferoxamine had only a slightly inhibitory effect. Similar results to those obtained using cumene-OOH were obtained utilizing tert-butyl-OOH in place of cumene-OOH. The yields of free radicals were in the order of glutathione > cysteine > penicillamine > N-acetylcysteine. Incubation of Co(II) with cumene-OOH ort-butyl-OOH in the presence of the histidyl oligopeptide Gly-Gly-His also generated lipid hydroperoxide-derived free radicals, with the yield being comparable to that obtained using thiols. In contrast, histidine, anserine, homocarnosine, or carnosine did not cause any free radical generation from Co(II) and lipid hydroperoxides. Incubation of Co(II) with H2)2 produced only a small amount of . OH radicals. (ABSTRACT TRUNCATED AT 250 WORDS)
Flexible Formation Control for Obstacle Avoidance Based on Numerical Flow Field

This paper presents a novel approach to obstacle avoidance for a group of robots moving in formation. This idea is originally inspired by a phenomenon in hydrodynamics. In this approach, a virtual robot is introduced as a reference point (beacon) to determine a collision-free trajectory. Taking the virtual point as a basic point, the robot group establish a rigid body-like formation. Since the collision-freeness of the virtual robot does not guarantee all other robots avoiding obstacles, we employ a flexible formation control scheme in the framework of rigid body-like formation. Two kinds of transformation are introduced to help every robot negotiate obstacles. This approach gives a new principle to deal with obstacle avoidance in formation control for multi-robot system. Simulation results are presented to verify its effectiveness
Diflubenzuron for Control of the Boll Weevil in Unisolated Cotton Fields

In a 1976 test in unisolated cotton fields, different rates (35, 70, and 140 g AI/ha) of the insect growth regulator diflubenzuron, N -[[(4-chloropheny)amino]carbonyl]-2,6-difluorobenzamide, were applied aerially over a 6-wk period to suppress populations of Anthonomus grandis Boheman. There was a pronounced dosage rate response to the chemical in that the percentage emergence of adult weevils from cotton squares collected from treated fields averaged 37.7, 22.2, and 15.8% at the lowest, median, and highest rate, respectively. Adult emergence from squares collected in untreated control plots averaged 70% during the same period. The reduction in weevil emergence was most pronounced in the F1 generation and somewhat less in the F2 and F3 generations. A similar emergence pattern was observed in 1977 but due to a delay in the initial treatment the effect lagged by 1 generation. In both years, there was an apparent rebound by pest populations during the latter part of the season as indicated by increased emergence from the field collected squares. This result was attributed to movement of untreated weevils into the treated fields.
[Diagnosis of health conditions in a pan-mining community in the Tapajós River Basin, Itaituba, Par , Brazil, 1992].

The purpose of this article is to describe health conditions in a pan-mining community, in particular the interaction of mercury contamination with other health problems. This study was carried out in a panning mine located on Rato Creek, a tributary of the Tapajó s River Basin in the municipality of Itaituba, State of Par The study population consisted of 223 individuals. An epidemiological questionnaire was applied, medical treatment was given, and biological specimens were collected. Testing of fecal samples showed that 96.1% of the individuals had parasites and 66.4% were anemic. Prevalence of hepatitis B virus was 85.0%, and 11 individuals (6.0%) were virus carriers (HBsAg positive). Of 186 patients tested for malaria, 65 individuals (35.0%) had the infection, of whom 34 (52.3%) were asymptomatic. Prevalence of syphillis was 41.6%. Urine mercury levels were measured in 173 individuals. Some 16 (9.2%) of those tested had mercury levels between 10 and 19 ug/l, while 9 patients (5.2%) had levels above 20 ug/l. An overview of general health conditions showed a combination of problems in individuals, who lacked adequate diagnosis, in addition to a high level of self-medication, given the absence of health facilities. In addition, these individuals are threatened by critical levels of mercury contamination. In conclusion, this article gives a general overview of health conditions in these pan-mining communities, demonstrating the multicausal nature of health conditions in the Amazon region, a fact which should be considered when planning appropriate strategies for clinical treatment.
Iowa State University From the SelectedWorks of Anupam Sharma October 10 , 2004 Numerical simulation of the blast impact problem using the Direct Simulation Monte Carlo ( DSMC ) method

A particle approach using the Direct Simulation Monte Carlo (DSMC) method is used to solve the problem of blast impact with structures. A novel approach to model the solid boundary condition for particle methods is presented. The solver is validated against an analytical solution of the Riemann shocktube problem and against experiments on interaction of a planar shock with a square cavity. Blast impact simulations are performed for two model shapes, a box and an I-shaped beam, assuming that the solid body does not deform. The solver uses domain decomposition technique to run in parallel. The parallel performance of the solver on two Beowulf clusters is also presented.
Design, Simulation and Testing of a High Speed Low Power 15-4 Compressor for High Speed Multiplication Applications

The paper presents a novel high speed and low power 15-4 Compressor for high speed and low power multiplication applications. The proposed compressor uses bit sliced adder architecture to exploit the parallelism in the computation of sum of 15 input bits by five full adders. The newly proposed compressor is also centered around the design of a novel 5-3 compressor that attempts to minimize the stage delays of a conventional 5-3 compressor that is designed using single bit full adder and half adder architectures. The proposed 15-4 compressor uses the minimum number of hardware resources so far as the logic level architecture of the design is concerned. The proposed compressor is tested using 14 transistor and 10 transistor adder designs reported in literature. The power delay product of the proposed compressor is found to be equal to as low as 0.98fJ using 10T adder design and 0.46fJ using 14T adder design. The whole simulation has been carried out using TSPICE using 0.35 mum technology.
Surface-functionalized cockle shell–based calcium carbonate aragonite polymorph as a drug nanocarrier

Calcium carbonate aragonite polymorph nanoparticles derived from cockle shells were prepared using surface functionalization method followed by purification steps. Size, morphology, and surface properties of the nanoparticles were characterized using transmission electron microscopy, field emission scanning electron microscopy, dynamic light scattering, zetasizer, X-ray powder diffraction, and Fourier transform infrared spectrometry techniques. The potential of surface-functionalized calcium carbonate aragonite polymorph nanoparticle as a drug-delivery agent were assessed through in vitro drug-loading test and drug-release test. Transmission electron microscopy, field emission scanning electron microscopy, and particle size distribution analyses revealed that size, morphology, and surface characterization had been improved after surface functionalization process. Zeta potential of the nanoparticles was found to be increased, thereby demonstrating better dispersion among the nanoparticles. Purification techniques showed a further improvement in the overall distribution of nanoparticles toward more refined size ranges <100 nm, which specifically favored drug-delivery applications. The purity of the aragonite phase and their chemical analyses were verified by X-ray powder diffraction and Fourier transform infrared spectrometry studies. In vitro biological response of hFOB 1.19 osteoblast cells showed that surface functionalization could improve the cytotoxicity of cockle shell–based calcium carbonate aragonite nanocarrier. The sample was also sensitive to pH changes and demonstrated good abilities to load and sustain in vitro drug. This study thus indicates that calcium carbonate aragonite polymorph nanoparticles derived from cockle shells, a natural biomaterial, with modified surface characteristics are promising and can be applied as efficient carriers for drug delivery.
Coadministration of co-trimoxazole with sulfonylureas: hypoglycemia events and pattern of use.

BACKGROUND Coadministration of co-trimoxazole with sulfonylureas is reported to increase the risk of hypoglycemia. METHODS We identified a cohort of Medicare beneficiaries aged 66 years or older who took glyburide or glipizide for diabetes from a 5% national sample of Medicare Part D claims data in 2008 (n = 34,239). We tracked each participant's claims during 2008-2010 for a co-trimoxazole prescription and subsequent emergency room visits for hypoglycemia. Descriptive statistics and logistic regression modeling were used to evaluate hypoglycemia-related emergency room visits after coadministration of co-trimoxazole with sulfonylureas and its utilization patterns in older adults with diabetes. RESULTS Sulfonylureas users prescribed co-trimoxazole had a significant higher risk of emergency room visits for hypoglycemia, compared with those prescribed noninteracting antibiotics (odds ratio = 3.89, 95% confidence interval = 2.29-6.60 for glipizide and odds ratio = 3.78, 95% confidence interval = 1.81-7.90 for glyburide with co-trimoxazole, using amoxicillin as the reference). Co-trimoxazole was prescribed to 16.9% of those taking glyburide or glipizide during 2008-2010, varying from 4.0% to 35.9% across U.S. hospital referral regions. Patients with polypharmacy and with more prescribers were more likely to receive co-trimoxazole. Patients with an identifiable primary care physician had 20% lower odds of receiving a co-trimoxazole prescription. Hospital referral regions with more PCPs had lower rates of coadministration of the two drugs (r = -.26, p < 0.001). CONCLUSIONS Coadministration of co-trimoxazole with sulfonylureas is associated with increased risk of hypoglycemia, compared with noninteracting antibiotics. Such coadministration is prevalent among older diabetic patients in the United States, especially in patients without an identifiable primary care physician.
End-stage renal disease: in vivo diffusion-tensor imaging of silent white matter damage.

PURPOSE To characterize and compare regional differences in anisotropy in patients with end-stage renal disease (ESRD) and in control subjects to understand the effect of ESRD and hemodialysis on the microstructures of white matter. MATERIALS AND METHODS This study was approved by an institutional review board; written informed consent was obtained. From March 2007 to December 2007, 34 patients (16 men, 18 women; mean age, 40.0 years; range, 26-50 years) with ESRD who were undergoing dialysis and 35 control subjects (16 men, 19 women; mean age, 38.3 years; range, 25-49 years) were enrolled. There was no significant sex or age difference between the ESRD and control groups. By using a 1.5-T imager, fractional anisotropy (FA) data obtained at diffusion-tensor magnetic resonance (MR) imaging (echo-planar imaging, 33 directions; b value, 1000 sec/mm(2)) and at T2-weighted fluid-attenuated inversion recovery (FLAIR) MR imaging of the bilateral parietal, frontal, occipital, and temporal lobe white matter, as well as the genu and splenium of the corpus callosum, were compared. The Cognitive Abilities Screening Instrument (CASI) was administered to all participants at imaging. RESULTS The ESRD group had significantly lower FA values in all regions than the control group. FA values were generally lower in older patients and in those who had been undergoing dialysis for a longer duration. Duration of dialysis was more often than age found to be correlated with differences in FA values. In areas in which there was a significant correlation between age, duration, and FA values, the regression coefficients were greater for those who had been undergoing dialysis longer than for those who were older. Patients with ESRD had significantly lower CASI scores than control subjects (P = .03). There were no significant group differences in FLAIR values (P = .25-.89). CONCLUSION Changes in FA values may be used to follow-up white matter changes in patients with ESRD who are undergoing maintenance dialysis. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls. org/cgi/content/full/2523080484/DC1.
Proposed function of alternative oxidase in mitochondrial sulphide oxidation detoxification in the Echiuran worm, Urechis unicinctus

Alternative oxidase (AOX), a ubiquinol oxidase, introduces a branch pathway to the respiratory electron transport chain (ETC), bypassing complexes III and IV and catalysing the cyanide-resistant reduction of oxygen to water without translocation of protons across the inner mitochondrial membrane. Thus, it functions as a non-energy-conserving member of respiratory ETC. Previous studies of AOX focused on plants and some fungi, whereas data on animals are limited. In this study, full-length AOX cDNA was cloned from the Echiuran worm, Urechis unicinctus, a marine benthic invertebrate. In addition, mRNA expression pattern of combined activity of cytochrome c oxidase (CCO) in the body wall and hindgut of the worm exposed in sulphide (50 µM and 150 µM) was measured. The results revealed that AOX mRNA expression increased in a time- and concentration-dependent manner in both tissues, was significantly increased at 48 h, and continuously increased with time. In contrast, the activity of CCO decreased significantly at 24 h and was inhibited at 48 h during exposure to 150 µM sulphide. The present data indicate the expression of AOX mRNA depended on the sulphide concentration present as well as being influenced by the physical condition of the worm, especially the CCO activity.