Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease

Though Abl inhibitors are often successful therapies for the initial stages of chronic myelogenous leukemia (CML), refractory cases highlight the need for novel molecular insights. We demonstrate that mice deficient in the enzyme 12/15-lipoxygenase (12/15-LO) develop a myeloproliferative disorder (MPD) that progresses to transplantable leukemia. Although not associated with dysregulation of Abl, cells isolated from chronic stage 12/15-LO–deficient (Alox15) mice exhibit increased activation of the phosphatidylinositol 3–kinase (PI3-K) pathway, as indicated by enhanced phosphorylation of Akt. Furthermore, the transcription factor interferon consensus sequence binding protein (ICSBP) is hyperphosphorylated and displays decreased nuclear accumulation, translating into increased levels of expression of the oncoprotein Bcl-2. The ICSBP defect, exaggerated levels of Bcl-2, and prolonged leukemic cell survival associated with chronic stage Alox15 MPD are all reversible upon treatment with a PI3-K inhibitor. Remarkably, the evolution of Alox15 MPD to leukemia is associated with additional regulation of ICSBP on an RNA level, highlighting the potential usefulness of the Alox15 model for understanding the transition of CML to crisis. Finally, 12/15-LO expression suppresses the growth of a human CML–derived cell line. These data identify 12/15-LO as an important suppressor of MPD via its role as a critical upstream effector in the regulation of PI3-K–dependent ICSBP phosphorylation.
Live Scanning Electron Microscope Observations of Dendritic Growth in Lithium/Polymer Cells

We report live observations of lithium polymer batteries upon cycling within the microscope antechamber by means of a scanning electron microscope, equipped with a transfer system that avoids sample air exposure. The well-established direct correlation between current density and dendrite formation is confirmed, and the formation of a mossy or dendritic interface was evidenced to be at the origin of the delaminating between the substrate, where the lithium is plated, and the polymer. These experiments enable a better understanding of the dendrite formation mechanism, like the important finding that they grow tipwise as well as sidewise. © 2002 The Electrochemical Society. All rights reserved.
Pharmacological Characterization of the Nociceptin/Orphanin FQ Receptor Antagonist SB-612111 [(–)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: In Vivo Studies

The excellent pharmacological profile displayed by the selective nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonist SB-612111 [(–)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol] in vitro prompted us to investigate the actions of this compound in vivo. In the mouse tail withdrawal assay, SB-612111 given i.p. up to 3 mg/kg did not modify per se tail withdrawal latencies but was able to prevent the pronociceptive and the antinociceptive action of 1 nmol of N/OFQ given i.c. v. and i.t. , respectively. In food intake studies performed in sated mice, SB-612111 (1 mg/kg i.p.) had no effect on food consumption but fully prevented the orexigenic effect of 1 nmol of N/OFQ i.c. v. In 17-h food-deprived mice, the opioid receptor antagonist naltrexone (1 mg/kg s.c.), but not SB-612111 (1 and 10 mg/kg i.p.), produced a statistically significant reduction of food intake. In the mouse forced swimming and tail suspension tests, SB-612111 (1–10 mg/kg) reduced immobility time. The antidepressant-like effect elicited by SB-612111 in the forced swimming test was reversed by the i.c. v. injection of 1 nmol of N/OFQ and no longer evident in mice knockout for the NOP receptor gene. In conclusion, the present findings demonstrate that SB-612111 behaves in vivo as a potent and selective NOP antagonist and suggest that the N/OFQ-NOP receptor endogenous system plays an important role in regulating mood-related behaviors. The use of SB-612111 in future pathophysiological studies will certainly contribute to define the therapeutic potential of selective NOP receptor antagonists in different disease areas.
Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis.

A high-density phylogenetic microarray targeting small subunit rRNA (SSU rRNA) sequences of over 1000 microbial phylotypes of the human gastrointestinal tract, the HITChip, was used to assess the impact of faecal inoculum preparation and operation conditions on an in vitro model of the human large intestine (TIM-2). This revealed that propagation of mixed faecal donations for the production of standardized inocula has only a limited effect on the microbiota composition, with slight changes observed mainly within the Firmicutes. Adversely, significant shifts in several major groups of intestinal microbiota were observed after inoculation of the in vitro model. Hierarchical cluster analysis was able to show that samples taken throughout the inoculum preparation grouped with microbiota profiles observed for faecal samples of healthy adults. In contrast, the TIM-2 microbiota was distinct. While members of the Bacteroidetes and some groups within the Bacilli were increased in TIM-2 microbiota, a strong reduction in the relative abundance of other microbial groups, including Bifidobacterium spp. , Streptococcus spp. , and Clostridium clusters IV and XIVa, was observed. The changes detected with the HITChip could be confirmed using denaturing gradient gel electrophoresis (DGGE) of SSU rRNA amplicons.
Isolation and properties of enhancer‐bypass mutants of sigma 54

The N‐terminal activation domain of Escherichia coli sigma 54 was randomly mutated to provide a library of changes that might allow the required enhancer function to be bypassed. Five clones harbouring mutant sigma factors were obtained that exhibited this property in that they enhanced growth under nitrogen‐limiting conditions in cells lacking NtrC. DNA sequence analysis located all mutations to four leucines in a small region between amino acids 25 and 31. No mutant sigma factors retained the hydrophobic character of the leucine residues. Mutant sigma factors were shown to transcribe in vitro without the need for enhancer binding activator or ATP hydrolysis, confirming the in vivo phenotype. These and other data suggest that a very small set of leucines is critical for keeping polymerase function in check, allowing high responsiveness to physiological induction via enhancer proteins such as NtrC.
Child Labor and Household Wealth: Theory and Empirical Evidence of an Inverted-U

Some studies on child labor have shown that greater land wealth leads to higher child labor, thereby casting doubt on the hypothesis that child labor is caused by poverty. This paper argues that the missing ingredient is an explicit modeling of the labor market. We develop a simple model which suggests an inverted-U relationship between land holdings and child labor. A unique data set from India that has child labor hours information confirms this hypothesis. It is shown that the turning point beyond which more land leads to a decline in child labor occurs at 3.6 acres of land per household, which is well below the observed maximum value of land-holding.
Effect of increased MRI and CT scan utilization on clinical decision-making in patients referred to a surgical clinic for back pain.

BACKGROUND We sought to determine the association between radiologic and clinical diagnoses and to measure the impact of more magnetic resonance imaging (MRI) and computed tomography (CT) scans on clinical decision-making in patients referred to a surgical clinic for back pain. METHODS We conducted a 7-week prospective study of patients referred for back pain to spine surgeons in 1 health care centre. Patients were included if they had not previously been seen by a surgeon for their back problems and if their back pain was related to the thoracic or lumbar spine. We collected demographic data, imaging findings, clinical diagnoses as determined by the surgeons and visit outcomes and compared our results with those of a similar study conducted in 1996. RESULTS Of 160 patients, 8 (5%) were no-shows and excluded from further analysis owing to incomplete data. There were more MRI scans and fewer plain radiographs ordered in 2009 compared with 1996 (73% v. 11% and 39% v. 68%, respectively). Degenerative disc disease was a more common radiologic diagnosis (n=78, 63%) than clinical diagnosis (n=41, 27%). Disc herniation was a more common radiologic diagnosis (n=69, 56%) than clinical diagnosis (n=25, 16%). With regards to visit outcomes, there were fewer second opinions sought in 2009 compared with 1996 (3% v. 11%). Although not statistically significant, the number of surgical candidates remained relatively stable (19% in 1996 v. 16% in 2009, p=0.44). CONCLUSION The clinical diagnosis had a poor association with radiologic abnormalities. Despite an increase in the number of MRI and CT scans, the number of patients deemed surgical candidates has not changed.
Job stressors of New Zealand dentists and their coping strategies.

BACKGROUND Dentistry is understood to be a stressful profession. Although there has been recent research about stress and dentistry in the UK and the Netherlands, little is known about the job stressors and coping strategies of New Zealand dentists. AIM To investigate job stressors and coping strategies among New Zealand dentists. METHODS A nationwide postal survey of a representative sample of 700 dentists. RESULTS The response rate was 65%. The most commonly reported stressors were treating difficult children (52%), constant time pressure (48%) and maintaining high levels of concentration (43%). The strategies most utilized for managing work-related stress included interactions with people (78%), sports (64%) and forgetting about work (59%). Dentists who had graduated overseas reported more sources of stress than New Zealand graduates. There were differences in the strategies used by male and female practitioners to manage stress. CONCLUSIONS There is considerable variation in the number of stressors experienced by dentists. Overseas-qualified dentists appear to be under more stress than New Zealand-trained dentists and may need greater professional support. Dentists should be encouraged to make greater use of active coping strategies.
Arteriogenic Therapy by Intramyocardial Sustained Delivery of a Novel Growth Factor Combination Prevents Chronic Heart Failure

Background— Therapeutic angiogenesis is a promising approach for the treatment of cardiovascular diseases, including myocardial infarction and chronic heart failure. We aimed to improve proangiogenic therapies by identifying novel arteriogenic growth factor combinations, developing injectable delivery systems for spatiotemporally controlled growth factor release, and evaluating functional consequences of targeted intramyocardial growth factor delivery in chronic heart failure. Methods and Results— First, we observed that fibroblast growth factor and hepatocyte growth factor synergistically stimulate vascular cell migration and proliferation in vitro. Using 2 in vivo angiogenesis assays (n=5 mice per group), we found that the growth factor combination results in a more potent and durable angiogenic response than either growth factor used alone. Furthermore, we determined that the molecular mechanisms involve potentiation of Akt and mitogen-activated protein kinase signal transduction pathways, as well as upregulation of angiogenic growth factor receptors. Next, we developed crosslinked albumin-alginate microcapsules that sequentially release fibroblast growth factor-2 and hepatocyte growth factor. Finally, in a rat model of chronic heart failure induced by coronary ligation (n=14 to 15 rats per group), we found that intramyocardial slow release of fibroblast growth factor-2 with hepatocyte growth factor potently stimulates angiogenesis and arteriogenesis and prevents cardiac hypertrophy and fibrosis, as determined by immunohistochemistry, leading to improved cardiac perfusion after 3 months, as shown by magnetic resonance imaging. These multiple beneficial effects resulted in reduced adverse cardiac remodeling and improved left ventricular function, as revealed by echocardiography. Conclusion— Our data showing the selective advantage of using fibroblast growth factor-2 together with hepatocyte growth factor suggest that this growth factor combination may constitute an efficient novel treatment for chronic heart failure.
Experimental validation of theoretical models for the frequency response of atomic force microscope cantilever beams immersed in fluids

Detailed measurements of the frequency responses of a series of rectangular atomic force microscope (AFM) cantilever beams, immersed in a range of fluids, have been performed to test the validity and accuracy of the recent theoretical model of Sader [J. Appl. Phys. 84, 64 (1998)]. This theoretical model gives the frequency response of a cantilever beam, that is immersed in a viscous fluid and excited by an arbitrary driving force. Very good agreement between experimental measurements and theoretical calculations is found for all fluids considered. Furthermore, a critical assessment of the well-known inviscid model is presented, which demonstrates that this model is not applicable to AFM cantilever beams in general.
Sound Sculpting: Manipulating Sound through Virtual Sculpting

We have prototyped sound sculpting, an environment in which a sound artist or musician can create, edit or perform sounds by changing parameters, like position, orientation and shape of a virtual object as input device, that can only be perceived through its visual and acoustic representations. We implemented sound sculpting by extending a realtime, visual programming language called Max/FTS, which was originally designed for sound synthesis, with software objects to interface datagloves and 6DOF sensors and to compute human movement and virtual object features. To date, we have performed two pilot studies, involving a virtual input device with a behaviour of a rubber balloon and another with a behaviour of a rubber sheet for the control of sound spatialization and timbre parameters. It was found that the more physical analogies are used for a mapping the faster the mapping can be learned. This requires more research for mapping virtual object features to timbre naturally. While both hands can be used for manipulation, left-hand-only sound sculpting may be a useful replacement for and extension of the standard keyboard modulation wheel. While we have succesfully implemented and tested virtual sculpting as a new real-time interaction method for sound design and musical performance, we need to address more manipulation pragmatics in the mapping and more carefully identify movement features to map to virtual object parameters.
Lupus Nephritis

Background Lupus nephritis, one of the most serious manifestations of systemic lupus erythematosus (SLE), usually arises within 5 years of diagnosis; however, renal failure rarely occurs before American College of Rheumatology classification criteria are met. Lupus nephritis is histologically evident in most patients with SLE, even those without clinical manifestations of renal disease. The symptoms of lupus nephritis are generally related to hypertension, proteinuria, and renal failure. With the advent of more aggressive immunosuppressive and supportive therapy, rates of renal involvement and patient survival are improving.
PAUSED, a Putative Exportin-t, Acts Pleiotropically in Arabidopsis Development But Is Dispensable for Viability1[w]

Exportin-t was first identified in humans as a protein that mediates the export of tRNAs from the nucleus to the cytoplasm. Mutations in Los1p, the Saccharomyces cerevisiae exportin-t homolog, result in nuclear accumulation of tRNAs. Because no exportin-t mutants have been reported in multicellular organisms, the developmental functions of exportin-t have not been determined. Here, we report the isolation and characterization of two Arabidopsis exportin-t mutants, paused-5 and paused-6. The mutant phenotypes indicate that exportin-t acts pleiotropically in plant development. In particular, paused-5 and paused-6 result in delayed leaf formation during vegetative development. The two paused mutations also cause the transformation of reproductive organs into perianth organs in the hua1-1 hua2-1 background, which is partially defective in reproductive organ identity specification. The floral phenotypes of hua1-1 hua2-1 paused mutants resemble those of mutations in the floral homeotic gene AGAMOUS. Moreover, paused-5 enhances the mutant phenotypes of two floral meristem identity genes, LEAFY and APETALA1. The developmental defects caused by paused mutations confirm the important roles of exportin-t in gene expression in multicellular organisms. In addition, a paused null allele, paused-6, is still viable, suggesting the presence of redundant tRNA export pathway(s) in Arabidopsis.
Comparison of transcriptional synergy of estrogen receptors alpha and beta from multiple tandem estrogen response elements.

Estrogen receptors alpha and beta (ERalpha and ERbeta) act as ligand-dependent transcriptional enhancers. We reported that ERalpha induces synergistic activation of luciferase reporter gene activity in response to E(2) from three or four tandem copies of a consensus estrogen response element (ERE) in transiently transfected MCF-7 cells. Here we addressed three questions: (1) is the synergistic activation of reporter gene activity from multiple tandem EREs by ERalpha restricted to MCF-7 cells? ; (2) does ERbeta induce synergistic activation of reporter activity from multiple tandem EREs? ; and (3) does ERbeta bind cooperatively to multiple tandem EREs? To address the first two questions, ER-negative CHO-K1 cells were co-transfected with ERalpha or ERbeta and ERE-driven reporter plasmids. Both ERalpha and ERbeta activated ERE-driven luciferase gene activity in an estradiol-dependent manner. Induction by ERbeta was lower than ERalpha from each ERE. We demonstrate that both ERalpha and ERbeta induce transcriptional synergy with three or four, but not two, tandem copies of an ERE. Electrophoretic mobility shift assays (EMSA) indicated an increase in ER-ERE binding affinity associated with cooperative binding of ERalpha and ERbeta to multiple EREs that may be responsible for transcriptional synergy in transiently transfected cells. We also postulate that interaction of ERalpha and ERbeta with coactivators may also play a role in transcriptional synergy.
The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and how to select an outcome measurement instrument

Background: COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) is an initiative of an international multidisciplinary team of researchers who aim to improve the selection of outcome measurement instruments both in research and in clinical practice by developing tools for selecting the most appropriate available instrument. Method: In this paper these tools are described, i.e. the COSMIN taxonomy and definition of measurement properties; the COSMIN checklist to evaluate the methodological quality of studies on measurement properties; a search filter for finding studies on measurement properties; a protocol for systematic reviews of outcome measurement instruments; a database of systematic reviews of outcome measurement instruments; and a guideline for selecting outcome measurement instruments for Core Outcome Sets in clinical trials. Currently, we are updating the COSMIN checklist, particularly the standards for content validity studies. Also new standards for studies using Item Response Theory methods will be developed. Additionally, in the future we want to develop standards for studies on the quality of non-patient reported outcome measures, such as clinician-reported outcomes and performance-based outcomes. Conclusions: In summary, we plea for more standardization in the use of outcome measurement instruments, for conducting high quality systematic reviews on measurement instruments in which the best available outcome measurement instrument is recommended, and for stopping the use of poor outcome measurement instruments.
Improving Statistical MT through Morphological Analysis

In statistical machine translation, estimating word-to-word alignment probabilities for the translation model can be difficult due to the problem of sparse data: most words in a given corpus occur at most a handful of times. With a highly inflected language such as Czech, this problem can be particularly severe. In addition, much of the morphological variation seen in Czech words is not reflected in either the morphology or syntax of a language like English. In this work, we show that using morphological analysis to modify the Czech input can improve a Czech-English machine translation system. We investigate several different methods of incorporating morphological information, and show that a system that combines these methods yields the best results. Our final system achieves a BLEU score of . 333, as compared to . 270 for the baseline word-to-word system.
Identification of Early Biomarkers during Acetaminophen-Induced Hepatotoxicity by Fourier Transform Infrared Microspectroscopy

Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra of acetaminophen treated livers in BALB/c mice show decrease in glycogen, increase in amounts of cholesteryl esters and DNA respectively. Rescue experiments using L-methionine demonstrate that depletion in glycogen and increase in DNA are abrogated with pre-treatment, but not post-treatment, with L-methionine. This indicates that changes in glycogen and DNA are more sensitive to the rapid depletion of glutathione. Importantly, analysis of sera identified lowering of glycogen and increase in DNA and chlolesteryl esters earlier than increase in alanine aminotransferase, which is routinely used to diagnose liver damage. In addition, these changes are also observed in C57BL/6 and Nos2 −/− mice. There is no difference in the kinetics of expression of these three molecules in both strains of mice, the extent of damage is similar and corroborated with ALT and histological analysis. Quantification of cytokines in sera showed increase upon APAP treatment. Although the levels of Tnfα and Ifnγ in sera are not significantly affected, Nos2 −/− mice display lower Il6 but higher Il10 levels during this acute model of hepatotoxicity. Overall, this study reinforces the growing potential of Fourier Transform Infrared microspectroscopy as a fast, highly sensitive and label-free technique for non-invasive diagnosis of liver damage. The combination of Fourier Transform Infrared microspectroscopy and cytokine analysis is a powerful tool to identify multiple biomarkers, understand differential host responses and evaluate therapeutic regimens during liver damage and, possibly, other diseases.