gebhart/patrepeval huggingface dataset:
Regulation of p70 S6 Kinase by Complex Formation between the Rac Guanine Nucleotide Exchange Factor (Rac-GEF) Tiam1 and the Scaffold Spinophilin (2003)

Tiam1 is a ubiquitous guanine nucleotide exchange factor (GEF) that activates the Rac GTPase. We have shown previously that the N terminus of Tiam1 contributes to the signaling specificity of its downstream target Rac via association with IB2, a scaffold that promotes Rac activation of a p38 kinase cascade. Here we show that the N terminus of Tiam1 can influence Rac signaling specificity in a different way by interaction with spinophilin, a scaffold that binds to p70 S6 kinase, another protein regulated by Rac. In particular, spinophilin binding promotes the plasma membrane localization of Tiam1 and enhances the ability of Tiam1 to activate p70 S6 kinase. In contrast, spinophilin binding suppresses the ability of Tiam to activate Pak1, a different Rac effector. Finally, a mutant spinophilin that cannot bind to Tiam1 suppresses serum-induced p70 S6 kinase activation in cells, suggesting that a Tiam1/spinophilin complex contributes to p70 S6 kinase regulation by extracellular signals. These findings add to a growing body of evidence supporting the concept that some Rac-GEFs not only activate Rac GTPases but also participate in the selection of Rac effector by binding to particular scaffolds that complex with components of specific Rac effector pathways.
COMPOSITION OF TWO SEAWEED-OLIGOSACCHARIDE-LYSATES DERIVED FROM AGARASE AS-II AND THEIR FERROUS-CHELATING ANTIOXIDANT POWER (2011)

Seaweed-oligosaccharide-lysates (SwOSLys) Gra-C108, Mon-C108, Gra-AS-II, or Mon-AS-II are seaweed polysaccharide extracts (SwPSExts) Gra or Mon, which are digested by either Aeromonas (A.) salmonicida MAEF108 crude agarases or Agarase AS-II that was produced from marine bacteria A. salmonicida MAEF108. High-performance liquid chromatography revealed that there were neoagarohexaose and neoagarotetraose in both Gra-C108 and Gra-AS-II and that neoagarooligosaccharide was absent in both Mon-C108 and Mon-AS-II. The polyphenol content of SwOSLys was higher than that of SwPSExts, though without significant difference (p < 0.05) on lysates, as digested by crude MAEF108-agarases or Agarase AS-II. Comparison of the chelating effects of GraC108 and Gra-AS-II on Fe2+ shows that not only do the polyphenolic compound but also the neoagarooligosaccharide show antioxidative properties.
Case Study: a Systems Approach to the Design of a Computer‐based Module for Teaching BASIC (1994)

Summary This study investigated whether 26 schoolteachers would benefit from a systematically designed computer‐based instruction (CBI) for learning the programming language of BASIC. The results indicated that the teachers did not perform well on either the immediate or delayed post‐test, nor did they hold a strong attitude toward the CBI module for learning BASIC. One of the possible reasons for these unexpected results might be that the learning content was too difficult or unfamiliar to most teachers. Recommendations for other BASIC instructors or software designers include the incorporation of an adequate amount of instruction for addressing common difficulties in learning BASIC. Also recommended are the integration of more practice opportunities for desired concepts and a higher level of learner control, in which the teachers can plan their own learning to review activities.
Relationship of seed quality traits for greenhouse-grown versus field-grown high erucic acid rapesseed: Is seed quality trait selection for greenhouse-grown seed worthwhile? (2008)

A study of the relationship of seed quality traits for greenhouse-grown and field-grown seed samples was conducted. Early generation high erucic acid rapeseed (HEAR) cross progeny were grown in the greenhouse, selfed and then the selfed seeds were grown in the field at the University of Manitoba. The oil, protein, erucic acid and glucosinolate concentrations of greenhouse-grown versus field-grown seed samples were compared. There were differences (P ≤ 0.01) between the means of all seed quality traits for greenhouse-grown versus field-grown seed samples. The mean oil, protein and erucic acid concentrations of field-grown seed samples were higher than for greenhouse-grown seed samples. In contrast, the mean glucosinolate concentration of greenhouse-grown seed samples was higher than for field-grown seed samples. Rank correlations between greenhouse-grown seed samples and field-grown seed samples for all seed quality traits were significant but moderate in magnitude. Selection for oil, protein, erucic acid and glucosinolate concentration in greenhouse-grown seed samples dramatically increased the number of high seed quality F 4 families in the field and was successful for all seed quality traits. It is concluded that seed quality selection in greenhouse-grown seed samples is worthwhile and that this procedure could lead to greater efficiencies in Brassica plant breeding programs. Key words: Rapeseed (Brassica napus L.), oil, protein, erucic acid, glucosinolates
PTG: An Abstraction for Unhindered Parallelism (2014)

Increased parallelism and use of heterogeneous computing resources is now an established trend in High Performance Computing (HPC), a trend that, looking forward to Exascale, seems bound to intensify. Despite the evolution of hardware over the past decade, the programming paradigm of choice was invariably derived from Coarse Grain Parallelism with explicit data movements. We argue that message passing has remained the de facto standard in HPC because, until now, the ever increasing challenges that application developers had to address to create efficient portable applications remained manageable for expert programmers.Data-flow based programming is an alternative approach with significant potential. In this paper, we discuss the Parameterized Task Graph (PTG) abstraction and present the specialized input language that we use to specify PTGs in our data-flow task-based runtime system, PaRSEC. This language and the corresponding execution model are in contrast with the execution model of explicit message passing as well as the model of alternative task based runtime systems. The Parameterized Task Graph language decouples the expression of the parallelism in the algorithm from the control-flow ordering, load balance, and data distribution. Thus, programs are more adaptable and map more efficiently on challenging hardware, as well as maintain portability across diverse architectures. To support these claims, we discuss the different challenges of HPC programming and how PaR-SEC can address them, and we demonstrate that in today's large scale supercomputers, PaRSEC can significantly outperform state-of-the-art MPI applications and libraries, a trend that will increase with future architectural evolution.
Toxicology and clinical potential of nanoparticles (2011)

In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called 'proof-of-principle' approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports.
Urban-Target Recognition by Means of Repeated Spaceborne SAR Images (2007)

The relative low resolution (~25 m times 5 m on the ground) of spaceborne C-band synthetic aperture radar (SAR) data as acquired, for example, by European Space Agency sensors ERS and Envisat, can be significantly increased (up to submeter precisions) by processing coherently long series of images. Moreover, by analyzing the amplitude of the radar signal and by exploiting polarization diversity, the main radar characteristics of urban targets can be estimated, and a system for automatic recognition of a set of scattering structures can be developed. In this paper, we study the variation of the amplitude of the received radar signal as a function of the acquisition geometry [normal baseline and Doppler centroid (DC)] to retrieve the extension of the targets in range and azimuth. The dependence of the radar amplitude on temperature at the time of acquisition has been discovered to be very useful to identify extended resonating targets. Dihedrals are discriminated from specular or trihedral reflectors through the phase of Envisat alternating polarization (AP) acquisitions. By means of all gathered radar measurements, the bases for the development of a system for the automatic recognition of six main typologies of urban SAR targets (ground-level and elevated backscatterers, simple and resonating dihedrals, poles and trihedrals) have been laid. Radar data are then combined with in situ surveys and aerial photos, allowing a first assessment of the methodology in urban area.
The mammalian Rad24 homologous to yeast Saccharomyces cerevisiae Rad24 and Schizosaccharomyces pombe Rad17 is involved in DNA damage checkpoint. (1998)

Cell cycle checkpoint proteins play critical roles in maintaining genomic stability and integrity to prevent the development of cancer and hereditary diseases. Here we report the isolation of a novel mouse gene encoding the protein MmRad24 [MmRad24 is the mouse homologue of HRad17, which was described recently by A. E. Parker et al. (J. Biol. Chem., 273: 18340-18346, 1998)], which shares significant sequence and structural homology with the budding yeast Rad24 and its fission yeast counterpart Rad17, both of which are required for DNA damage checkpoints. Confocal microscopy revealed that the green fluorescent protein-tagged MmRad24 protein is localized to the nucleus in living cells. Fluorescence-activated cell-sorting analysis showed that overexpression of the wild-type MmRad24 in diploid fibroblast WI-38 cells caused a significant G2 arrest of the cell cycle, whereas overexpression of a mutant MmRad24 (mutated on the nucleotide-binding site) that likely functions as a dominant-negative protein resulted in a defect in cell cycle arrest after DNA damage treatment as measured by bromodeoxyuridine pulse-chase labeling experiments. Taken together, these results suggest that the mammalian Rad24 protein may function as a critical gatekeeper in DNA damage checkpoint control.
Influence of sex, age, and menopausal state on the course of early rheumatoid arthritis. (2001)

Higher age at presentation of RA leads to a more severe disease course in terms of DAS, RJD, and HAQ. Although female sex has a deteriorating effect on the DAS, the menopausal state is responsible for the major part of the differences in outcome between men and women. Postmenopausal state in early RA influences future disability and damage, especially in older patients.
Emerging functions of p21‐activated kinases in human cancer cells (2002)

The p21 activated kinases (Paks), an evolutionarily conserved family of serine/threonine kinases, are important for a variety of cellular functions including cell morphogenesis, motility, survival, mitosis, and angiogenesis. Paks are widely expressed in numerous tissues and are activated by growth factors and extracellular signals through GTPase-dependent and -independent mechanisms. Overexpression of Paks in epithelial cancer cells has been shown to increase migration potential, increase anchorage independent growth, and cause abnormalities in mitosis. Dysregulation of Paks has been reported in several human tumors and neurodegenerative diseases. A growing list of novel Pak interacting proteins has opened up exciting avenues of investigation by which to understand the functions of Paks in tumorigenesis. In this review, we will summarize the current knowledge of the Paks family with respect to emerging cellular functions and possible contributions to cancer.
Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy (2017)

<i><b>Introduction:</b></i> Cancer is an intricate disorder/dysfunction of cells that can be defined as a genetic heterogeneity in human disease. Therefore, it is characterized by several adaptive complex hallmarks. Among them, the pH dysregulation appears as a symbol of aberrant functions within the tumor microenvironment (TME). In comparison with normal tissues, in the solid tumors, we face with an irregular acidification and alkalinization of the extracellular and intracellular fluids. <i><b>Methods:</b></i> In this study, we comprehensively discussed the most recent reports on the hallmarks of solid tumors to provide deep insights upon the molecular machineries involved in the pH dysregulation of solid tumors and their impacts on the initiation and progression of cancer. <i><b>Results:</b></i> The dysregulation of pH in solid tumors is fundamentally related to the Warburg effect and hypoxia, leading to expression of a number of molecular machineries, including: NHE1, H+ pump V-ATPase, CA-9, CA-12, MCT-1, GLUT-1. Activation of proton exchangers and transporters (PETs) gives rise to formation of TME. This condition favors the cancer cells to evade from the anoikis and apoptosis, granting them aggressive and metastasis phenotype, as well as resistance to chemotherapy and radiation therapy. This review aimed to discuss the key molecular changes of tumor cells in terms of bio-energetics and cancer metabolism in relation with pH dysregulation. During this phenomenon, the intra- and extracellular metabolites are altered and/or disrupted. Such molecular alterations provide molecular hallmarks for direct targeting of the PETs by potent relevant inhibitors in combination with conventional cancer therapies as ultimate therapy against solid tumors. <i><b>Conclusion:</b></i> Taken all, along with other treatment strategies, targeting the key molecular machineries related to intra- and extracellular metabolisms within the TME is proposed as a novel strategy to inhibit or block PETs that are involved in the pH dysregulation of solid tumors.
Anxiety Disorders in Children and Adolescents in the First Six Months After Traumatic Brain Injury (2011)

The study's objective was to assess the nature, rate, predictive factors, and neuroimaging correlates of novel (new-onset) definite anxiety disorders and novel definite/subclinical anxiety disorders (in a broader group of children with at least subclinical anxiety disorders) after traumatic brain injury (TBI). Children with TBI from consecutive admissions to five trauma centers were enrolled and studied with psychiatric interviews soon after injury (baseline) and again 6 months post-injury. Novel definite anxiety disorder and novel definite/subclinical anxiety disorders were heterogeneous and occurred in 8.5% (N=12) and 17% (N=24) of participants, respectively, in the first 6 months after injury. Novel definite anxiety disorder was significantly associated with younger age at injury and tended to be associated with novel depressive disorder, as well as lesions of the superior frontal gyrus. Novel definite/subclinical anxiety disorder was significantly associated with concurrent psychiatric problems of personality change due to TBI and novel definite/subclinical depressive disorder, as well as with lesions of the superior frontal gyrus and a trend-association with frontal lobe white-matter lesions. These findings suggest that anxiety after childhood TBI may be part of a broader problem of affective dysregulation related to damaged dorsal frontal lobe and frontal white-matter systems, with younger children being at greatest risk for developing novel anxiety disorder after TBI.
Diatom communities in the Gulf of Bothnia: their biodiversity, gradient responses and application in paleo-ecology. (2002)

Diatom communities in the Gulf of Bothnia: their biodiversity, gradient responses and application in paleo-ecology.
Monoclonal Antibodies for Diagnosis and Potential Therapy of Small Cell Lung Cancer—The Ganglioside Antigen Fucosyl-Gm<sub>1</sub> (1993)

Lung carcinomas represent a highly heterogenous group of tumors, which includes small cell lung cancer (SCLC). The ganglioside fucosyl-GM1 (FucGM1) was originally identified as a highly selective marker for SCLC. A number of monoclonal antibodies against FucGM1 have been produced against the purified ganglioside, and their specificity validated. With monoclonal antibodies, FucGM1 has been detected in tissues as well as in serum samples from SCLC patients. A sensitive, quantitative assay method for FucGM1 was developed based on scintillation proximity immunoassay (SPA): A specific monoclonal antibody against FucGM1 is bound to immunosorbent particles that contain a fluor. When radiolabelled FucGM1 binds to these particles, the fluor is excited, and the photons emitted can be measured directly in a beta-counter. This sensitive assay for FucGM1 has several potential diagnostic applications: differential diagnosis of SCLC, development of serum assays for diagnosis and monitoring of disease progression, and monitoring of patient response to therapy. The expression of FucGM1 in SCLC cells is heterogeneous, and may depend on the differentiated state of tumor cells. However, monoclonal antibodies specific for FucGM1 may have important future applications for radioimmunoimaging as well as in immunotherapy for SCLC.
Reversal of social deficits by subchronic oxytocin in two autism mouse models (2016)

Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-d-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia-like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders.
Anti-proliferative activity of a new class of taxanes (14β-hydroxy-10-deacetylbaccatin III derivatives) on multidrug-resistance-positive human cancer cells (1997)

Paclitaxel, docetaxel and a series of new analogs synthesized from 14beta-hydroxy-10-deacetylbaccatin III (14-OH-DAB), a natural diterpene closely related to the core synthon of the 2 above prototypes, were tested in vitro for their growth-inhibitory activity on different human cancer cell lines, including some expressing the classic multidrug-resistant (MDR) phenotype (MCF-7 ADRr and CEM VBLr). The 14-OH-DAB derivatives showed enhanced anti-proliferative activity as compared to the parent compounds on the MDR-positive cancer cell lines. Particularly, IDN 5109 showed a 25- to 30-fold higher activity than paclitaxel. The fold change in activity between paclitaxel and analogs (IC50 paclitaxel/IC50 analogs) on the MDR-positive cell lines was calculated and a significant correlation observed. As far as the MDR-negative MDA-MB 231 cells are concerned, docetaxel and IDN 5109 exhibited a more potent activity than paclitaxel. On the basis of the data obtained on cell growth inhibition, we selected the most active compounds to study their effect on the cell cycle. Cell cycle analysis showed that all of the compounds tested were able to induce cell cycle block at G2/M in a concentration-dependent manner. The amount of cell block, measured as a G1/G2 ratio, was correlated significantly (p < 0.001) with apoptosis, as evaluated in the sub-G1 region (% of DNA fragmentation), thereby suggesting that the G2/M-blocked cells underwent apoptosis. To confirm the occurrence of apoptosis in this system, DNA gel agarose electrophoresis was performed and showed the typical ladder pattern.
Diving Response in Rats: Role of the Subthalamic Vasodilator Area (2016)

Diving response (DR) is a powerful integrative response targeted toward survival of the hypoxic/anoxic conditions. Being present in all animals and humans, it allows to survive adverse conditions like diving. Earlier, we discovered that forehead stimulation affords neuroprotective effect, decreasing infarction volume triggered by permanent occlusion of the middle cerebral artery in rats. We hypothesized that cold stimulation of the forehead induces DR in rats, which, in turn, exerts neuroprotection. We compared autonomic [AP, heart rate (HR), cerebral blood flow (CBF)] and EEG responses to the known DR-triggering stimulus, ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and cold stimulation of the glabrous skin of the tail base in anesthetized rats. Responses in AP, HR, CBF, and EEG to cold stimulation of the forehead and ammonia vapors instillation into the nasal cavity were comparable and differed significantly from responses to the cold stimulation of the tail base. Excitotoxic lesion of the subthalamic vasodilator area (SVA), which is known to participate in CBF regulation and to afford neuroprotection upon excitation, failed to affect autonomic components of the DR evoked by forehead cold stimulation or nasal mucosa ammonia stimulation. We conclude that cold stimulation of the forehead triggers physiological response comparable to the response evoked by ammonia vapor instillation into nasal cavity, which is considered as stimulus triggering protective DR. These observations may explain the neuroprotective effect of the forehead stimulation. Data demonstrate that SVA does not directly participate in the autonomic adjustments accompanying DR; however, it is involved in diving-evoked modulation of EEG. We suggest that forehead stimulation can be employed as a stimulus capable of triggering oxygen-conserving DR and can be used for neuroprotective therapy.
Highly differentiated human airway epithelial cells: a model to study host cell–parasite interactions in pertussis (2015)

The relevance of this model to study host-parasite interaction in pertussis lies in the striking physiologic and morphologic similarity between the PHAE and HBE cells and the human airway ciliated and goblet cells in vivo. These cells can proliferate in vitro, differentiate, and express the same genetic profile as human respiratory cells in vivo.