Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment with the MEK inhibitor U0126 induces decreased hyperpolarized pyruvate to lactate conversion in breast, but not prostate, cancer cells

Alterations in cell metabolism are increasingly being recognized as a hallmark of cancer and are being exploited for the development of diagnostic tools and targeted therapeutics. Recently, 13C MRS‐detectable hyperpolarized pyruvate to lactate conversion has been validated in models as a noninvasive imaging method for the detection of tumors and treatment response, and has successfully passed phase I clinical trials. To date, response to treatment has been associated with a decrease in hyperpolarized lactate production. In this study, we monitored the effect of treatment with the mitogen‐activated protein kinase (MEK) inhibitor U0126 in prostate and breast cancer cells. Following treatment, we observed a 31% decrease in the flux of hyperpolarized 13C label in treated MCF‐7 breast cancer cells relative to controls. In contrast, and unexpectedly, the flux increased to 167% in treated PC3 prostate cancer cells. To mechanistically explain these observations, we investigated treatment‐induced changes in the different factors known to affect the pyruvate to lactate conversion. NADH (nicotinamide adenine dinucleotide, reduced form) levels remained unchanged, whereas lactate dehydrogenase expression and activity, as well as intracellular lactate, increased in both cell lines, providing an explanation for the elevated hyperpolarized lactate observed in PC3 cells. The expression of MCT1, which mediates pyruvate transport, decreased in treated MCF‐7, but not PC3, cells. This identifies pyruvate transport as rate limiting in U0126‐treated MCF‐7 cells and explains the decrease in hyperpolarized lactate observed in these cells following treatment. Our findings highlight the complexity of interactions between MEK and metabolism, and the need for mechanistic validation before hyperpolarized 13C MRS can be used to monitor treatment‐induced molecular responses. Copyright © 2012 John Wiley & Sons, Ltd.
Individualized Monitoring of Nuclear Factor of Activated T Cells-Regulated Gene Expression in FK506-Treated Kidney Transplant Recipients

Background. The suggested key mechanism of both cyclosporine A (CsA) and FK506 is the inhibition of calcineurin phosphatase activity, preventing nuclear factor of activated T cells (NFAT)-translocation into the nucleus of T cells, with a subsequent transcriptional block of crucial cytokine genes. However, the two drugs exert different clinical activities as exemplified by the ability of FK506 to treat acute rejections. Inhibition of calcineurin activity by FK506 occurs in vitro at the same or even higher dose as for CsA; however, the magnitude of clinical and experimental immunosuppression is higher, indicating that FK506 may act in a calcineurin-independent way. Methods. To test this hypothesis, we measured the inhibition of NFAT-regulated gene expression in 262 stable kidney transplanted patients after FK506 intake. Results. Previously, we showed that the optimal degree of NFAT inhibition in patients treated with CsA is between 15% and 30% residual gene expression. A considerable number of patients treated with FK506 do not achieve this level of immunosuppression despite therapeutic drug concentrations. Importantly, FK506 does inhibit protein translation. This insufficient degree of NFAT inhibition was associated with a higher rate of biopsy-proven acute rejection but also with a lower incidence of recurrent infections. Conversion of CsA to FK506 causes immediately reduced inhibition of NFAT-regulated gene expression. Conclusion. We could demonstrate that a considerable number of FK506-treated patients benefit from the drug, irrespective of the potency of NFAT inhibition in T cells by a yet unknown mechanism. Nevertheless, residual expression of NFAT-regulated genes seems to be a useful pharmacodynamic method to monitor FK506 therapy in renal transplant patients.
Cardiovascular Disease Continuum- An Update

The objective of this study is to determine the various risk factors responsible for causing the cardiovascular disease like diabetes mellitus, dyslipidemia, hypertension, smoking and visceral adiposity. High cholesterol levels have long been considered an independent risk factor for cardiovascular disease. Diabetes mellitus, especially type 2 accounts for over 97% of the adult diabetic population. Lack of exercise and increased consumption of sweets, soft drinks and decreased consumption of fruits and vegetables has contributed increasingly to overweight and obesity in young persons and adults. Cigarette smoking and hypertension is a well established risk factor for cardiovascular disease continuum. There are hardly any studies assessing about the risk factors responsible for causing cardiovascular disease. Hence, this review will help in determining those factors responsible for cardiovascular disease continuum.
Apoptosis during development of the human retina: Relationship to foveal development and retinal synaptogenesis

Apoptosis in the ganglion cell (GCL) and inner nuclear (INL) layers of human fetal retinae aged 14–35 weeks of gestation (WG) was investigated in relation to synaptogenesis and foveal depression formation. Terminal transferase dUTP‐biotin nick end labeling (TUNEL) was used to identify apoptosis, and synapse development was demonstrated by synaptophysin immunoreactivity (‐IR). The distribution of apoptotic cells and synaptophysin‐IR was studied as a function of eccentricity. Between 14 and 23–24 WG in the GCL, rates of apoptosis were relatively low in central retina. A shallow fovea was detected at 23–24 WG. In the central GCL, the rate of apoptosis was 0.21% of viable cells compared with a higher incidence of 0.79–1.64% peripherally. Apoptosis in the INL was 2–8 times greater than that in the GCL. At 14–15 WG, peak death occurred at the incipient fovea; however, by 20 WG the distribution was bimodal, with peaks at more eccentric locations on either side of the incipient fovea with increasing age. Approximately 90% of INL apoptotic cells were in the middle and outer regions, suggesting that bipolar cells formed the majority of dying neurons. Synaptophysin‐IR was present in cones, bipolar cells, and processes in the inner and outer plexiform layers at the incipient fovea at 14 WG and spread peripherally with increasing age. The peripheral margin of synaptophysin‐IR coincided with areas of peak INL apoptosis. This pattern suggests that bipolar cell elimination is associated with the onset of synaptogenesis. Apoptosis in the GCL and INL is not a significant factor in foveal depression morphogenesis. J. Comp. Neurol. 413:198–208, 1999. © 1999 Wiley‐Liss, Inc.
Sebaceous Carcinoma Arising from Nevus Sebaceus: A Case Report

BACKGROUND Sebaceous carcinoma (SC) is a rare, aggressive, malignant tumor that is derived from adnexal epithelium of sebaceous glands that are distributed mostly in the skin of the head, neck, and hair-bearing regions of the body. OBJECTIVE To discuss the clinical and histologic features and the prognosis of the extraocular SC. METHOD We report a case of SCs of the scalp arising from a previous lesion clinically compatible with a nevus sebaceous. The lesion was surgically excised completely. RESULTS The postoperative course was free of complications, and the patient was clinically free of disease at her recent follow-up 2 years after treatment. CONCLUSIONS The absence of metastasis or cutaneous recurrence in our patient, notwithstanding the size of the lesion and its late removal, almost 25 years after the first signs of its growth, confirms a much improved prognostic behavior for extraocular SCs.
Visual learning given sparse data of unknown complexity

This study addresses the problem of unsupervised visual learning. It examines existing popular model order selection criteria before proposes two novel criteria for improving visual learning given sparse data and without any knowledge about model complexity. In particular, a rectified Bayesian information criterion (BICr) and a completed likelihood Akaike's information criterion (CL-AIC) are formulated to estimate the optimal model order (complexity) for learning the dynamic structure of a visual scene. Both criteria are designed to overcome poor model selection by existing popular criteria when the data sample size varies from very small to large. Extensive experiments on learning a dynamic scene structure are carried out to demonstrate the effectiveness of BICr and CL-AIC, compared to that of BIC (Schwarz, 1978), AIC (Akaike, 1973), ICL (Biernacki, 2000) and a MML (Figueiredo and Jain, 2002) based criterion.
THERAPEUTIC CHANGE, INNOVATIVE MOMENTS, AND THE RECONCEPTUALIZATION OF THE SELF: A DIALOGICAL ACCOUNT

Innovative moments (IMs) are exceptions toward the problematic self-narrative that brought the client to therapy, which emerge in the therapeutic conversation. Dialogically, an IM might be conceived as an expression of an alternative I-position which challenges the dominance of problematic voices, thus having the potential to transform the self-narrative as they are expanded and elaborated. Reconceptualization is a particular type of IM which usually emerges in the middle of the process of a successful treatment, increasing steadily until the end. Moreover, reconceptualization seems to be a distinctive feature of a successful psychotherapy process, as it is almost absent in poor outcome cases. This IM has two main features: the presence of a contrast between a previous self-narrative and a new emergent one, and the access to the process which allowed for the transformation from the former to the last. This innovative moment clearly involves a special I-position which Hermans has characterized as a meta- position. We discuss four functions of this type of IM in the change process: (1) providing a narrative structure for change; (2) bridging the past and present self-narratives; (3) facilitating the progressive identification with the new self-narrative; and (4) allowing surpassing the ambivalence often involved in the change process.
Optimization of cryoprotectant treatment for the vitrification of immature cumulus-enclosed porcine oocytes: comparison of sugars, combinations of permeating cryoprotectants and equilibration regimens

Our aim was to optimize the cryoprotectant treatment for the preservation of immature porcine cumulus-oocyte complexes (COCs) by solid surface vitrification. In each experiment, the vitrification solution consisted of 50 mg/ml polyvinyl pyrrolidone, 0.3 M of the actual sugar and in total 35% (v/v) of the actual permeating cryoprotectant (pCPA) combination. After warming, the COCs were subjected to in vitro maturation, fertilization and embryo culture. In Experiment 1, trehalose and sucrose were equally effective during vitrification and warming in terms of facilitating oocyte survival and subsequent embryo development. In Experiment 2, when equilibration was performed at 38.5 C in a total of 4% (v/v) pCPA for 15 min, the combination of ethylene glycol and propylene glycol (EG + PG = 1:1) was superior to EG and dimethyl sulfoxide (EG + DMSO = 1:1) in terms of oocyte survival after vitrification and the quality of resultant blastocysts. In Experiment 3, equilibration in 4% (v/v) pCPA for 15 min before vitrification was superior to that in 15% (v/v) CPA for 5 min for achievement of high survival rates irrespective of the pCPA combination used. In Experiment 4, when equilibration was performed in 4% EG + PG for 5 min, 15 min or 25 min, there was no difference in oocyte survival and subsequent embryo development after vitrification and warming; however, the developmental competence of cleaved embryos was tendentiously reduced when equilibration was performed for 25 min. In conclusion, trehalose and sucrose were equally effective in facilitating vitrification, and the optimum pCPA treatment was 5–15 min equilibration in 4% (v/v) of EG + PG followed by vitrification in 35% (v/v) EG + PG.
Identification and Quantification of Methanogenic Archaea in Adult Chicken Ceca

ABSTRACT By using molecular methods for the identification and quantification of methanogenic archaea in adult chicken ceca, 16S rRNA genes of 11 different phylotypes, 10 of which were 99% similar to Methanobrevibacter woesei, were found. Methanogen populations, as assessed by cultivation, and the 16S rRNA copy number were between 6.38 and 8.23 cells/g (wet weight) and 5.50 and 7.19 log10/g (wet weight), respectively.
SYNTACTIC PHRASE-BASED STATISTICAL MACHINE TRANSLATION

Phrase-based statistical machine translation (PBSMT) systems represent the dominant approach in MT today. However, unlike systems in other paradigms, it has proven difficult to date to incorporate syntactic knowledge in order to improve translation quality. This paper improves on recent research which uses 'syntactified' target language phrases, by incorporating supertags as constraints to better resolve parse tree fragments. In addition, we do not impose any sentence-length limit, and using a log-linear decoder, we outperform a state-of-the-art PBSMT system by over 1.3 BLEU points (or 3.51% relative) on the NIST 2003 Arabic-English test corpus.
Implicit representations of luminance and the temporal structure of moving stimuli in multiple regions of human visual cortex revealed by multivariate pattern classification analysis

The generation of a behaviorally relevant cue to the speed of objects around us is critical to our ability to navigate safely within our environment. However, our perception of speed is often distorted by prevailing conditions. For instance, as luminance is reduced, our perception of the speed of fast-moving patterns can be increased by as much as 30%. To investigate how the cortical representation of speed may vary under such conditions, we have measured the functional MRI blood oxygen level-dependent (BOLD) response of visual cortex to drifting sine gratings at two very different luminances. The average BOLD response in all areas was band-pass with respect to speed (or equivalently, temporal frequency) and thus contained no unambiguous speed information. However, a multivariate classifier was able to predict grating speed successfully in all cortical areas measured. Similarly, we find that a multivariate classifier can predict stimulus luminance. No differences in either the mean BOLD response or the multivariate classifier response with respect to speed were found as luminance changed. However, examination of the spatial distribution of speed preferences in the primary visual cortex revealed that perifoveal locations preferred slower speeds than peripheral locations at low but not high luminance. We conclude that although an explicit representation of perceived speed has yet to be demonstrated in the human brain, multiple visual regions encode both the temporal structure of moving stimuli and luminance implicitly.
Entrepreneurs, Risk Aversion, and Dynamic Firms

How do entrepreneurs vary firm size, capital structure, and default to manage risk? We show that more risk-averse entrepreneurs run smaller, more highly leveraged firms and default less, because running a smaller firm with higher debt reduces personal funds at risk in the firm. Optimal default depends on ex ante debt, consumption forgone from firm liquidation, and owner capacity to inject funds. We show that entrepreneurs sacrifice current consumption in the hope of future success that never materializes for the bottom 25 percent, but entrepreneurship is a path toward great wealth and high consumption for the top quartile.
Adenocarcinoma of the Mammary Gland in a Red Fox from Austria

A mammary gland adenocarcinoma was diagnosed in an adult red fox (Vulpes vulpes) which was shot in Austria in August 1995. Metastases were found in the kidneys and liver. This is the first reported case of an adenocarcinoma in a fox, and lack of mammary gland carcinoma in this species may be age related.
Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

Dual antiplatelet therapy with acetylsalicylic acid and a thienopyridine, such as clopidogrel, is effective for the secondary prevention of cardiovascular events in patients with acute coronary syndrome, but there is still a substantial residual risk of recurrence. Although anticoagulant therapy with a vitamin K antagonist (e.g. warfarin) in conjunction with antiplatelet therapy has been shown to reduce the risk of cardiovascular events, the rates of bleeding were increased with these combination therapies; hence, triple therapy with warfarin is currently only recommended in patients at low risk of bleeding. In addition, there are other limitations associated with vitamin K antagonist therapy, including the need for routine coagulation monitoring and dose adjustment to maintain the treatment within the therapeutic range. Rivaroxaban is an oral, direct Factor Xa inhibitor; in clinical practice, it is likely that rivaroxaban will be given to patients who also receive antiplatelet therapy, such as clopidogrel. This randomized, non-blinded, three-way crossover study investigated the effect of rivaroxaban on bleeding time when coadministered with clopidogrel. In addition, the influence of clopidogrel on the safety, tolerability, pharmacodynamics and pharmacokinetics of rivaroxaban was investigated. Of 27 healthy male subjects who received a single 300 mg dose of clopidogrel, 14 were identified as clopidogrel responders and were then randomized to the following three treatments: (A) two doses of clopidogrel on two consecutive days (300 mg on day 1; 75 mg on day 2); (B) one dose of rivaroxaban (15 mg); or (C) a combination of treatments A and B (rivaroxaban given on day 2). All treatments were well tolerated. Bleeding time with coadministration of rivaroxaban and clopidogrel was significantly prolonged in four subjects, compared with either drug alone: combination treatment increased the overall least squares-means to 3.77 times baseline (90% confidence interval [CI] 2.82–4.73), compared with 1.13 times baseline (90% CI 0.17–2.09) with rivaroxaban and 1.96 times baseline (90% CI 0.10–2.91) with clopidogrel. Co-administration of clopidogrel had no significant effect on the pharmacokinetics of rivaroxaban and, when compared with rivaroxaban alone, had no further effects on Factor Xa activity or prothrombin time. Inhibition of ADP-stimulated platelet aggregation by clopidogrel was not affected by rivaroxaban. As expected, owing to the mode of action of each study drug, the results of this study demonstrated that coadministration of the Factor Xa inhibitor rivaroxaban and the antiplatelet clopidogrel increased the bleeding time in healthy subjects without affecting other pharmacokinetic or pharmacodynamic parameters of each drug.
Stable polarization operation of 1.3-/spl mu/m wavelength vertical-cavity surface-emitting laser (VCSEL) fabricated by orientation-mismatched wafer bonding

We present stable polarization of a long-wavelength vertical-cavity surface-emitting laser (LW VCSEL). The polarization control was achieved through growing its active region on a (113)B InP substrate, which was integrated to [001] GaAs-based distributed Bragg reflectors by a wafer-bonding technique. Theoretical investigation showed that to achieve high polarization stability, a large dichroism such as an anisotropic gain is needed. It was also shown that the (113)B and other planes of the (11n) family have asymmetry, which results in asymmetric stress and anisotropic optical gain in a strained multiquantum well. An index-guiding mesa structure was fabricated in an asymmetric shape. The index guiding either enhanced or distracted the polarization stability originating from gain anisotropy, depending on its orientation of the asymmetry, as was confirmed by a statistical summary. Using a VCSEL with an appropriate index-guiding structure, we performed 1-Gb/s modulation and confirmed single polarization under large-signal modulation.
Monitoring Soil Moisture to Support Risk Reduction for the Agriculture Sector Using RADARSAT-2

Monitoring the amount of moisture held in the soil is critical in the management of risk for the agriculture sector. Extremes in soil moisture can lead to devastating consequences. Early assessment of soil moisture reserves, and monitoring of changes in available soil moisture, could assist in risk reduction strategies for the agriculture sector and effective delivery of government programs. Agriculture and Agri-Food Canada has been acquiring RADARSAT-2 data since 2008 to evaluate the accuracy with which this sensor can provide soil moisture to assist with implementing risk reduction strategies for the Canadian agriculture sector. The calibrated Integral Equation Model (IEM) was used to estimate soil moisture for 15 RADARSAT-2 data sets acquired over an eastern and western Canadian test site. Using this approach, field level soil moisture was estimated to a mean average error of 7.95%, although considerable scatter in the results was observed. Removing fields which had significant residue cover improved site specific soil moisture errors, but only for the fall campaign prior to spring tillage and seed bed preparation. Higher errors were also observed for data sets where angles between the RADARSAT-2 look direction and field tillage structures were largest. When soil moisture estimates were evaluated at a regional scale, mean errors fell to 3.14%. The IEM was also able to detect increases and decreases in soil moisture which followed periods of rainfall and drying.
What Is the True Covering Factor of Absorbing Matter in BALQSOs?

Spectropolarimetry of broad absorption line quasars (BALQSOs) has demonstrated that the geometry of the absorbing material is far from spherically symmetric. Calculations of accretion disk spectra suggest that the intrinsic radiation pattern of quasars is also anisotropic. Because the quasar count distribution is very steep, if the orientations of these two anisotropies are correlated, optical flux-limited samples would be very strongly biased with respect to the discovery of BALQSOs. In particular, currently favored models suggest that BALQSOs may be much more common than they appear in the samples. If so, the intrinsic covering fraction of absorbing matter must be relatively large. Numerous consequences follow, including the prediction of a new population of hard X-ray sources (as may have been seen already by ASCA) and a possible explanation for the anomalously strong N V λ1240 lines seen in many high-redshift quasars.
Evidence for a “Migrant Personality”: Attachment Styles of Poles in Poland and Polish Immigrants in the Netherlands

In the present study, we examined empirical evidence for a concept of a “migrant personality” using the attachment framework. We compared Polish immigrants in the Netherlands to the Poles living in Poland measuring their secure and dismissing attachment styles, while controlling for age, gender, and education in both samples. The results showed that immigrants are more secure and more dismissing than their fellow countrymen (p < .001). Furthermore, we examined, whether attachment styles might be influenced by the host culture. For that purpose, we subdivided the sample of immigrants into 11 cohorts (each cohort differentiated from the other by two more years of residence) and we compared the mean scores on secure and dismissing attachment styles in consecutive cohorts of immigrants. We observed that the mean scores on secure and dismissing attachment remained similar over cohorts of immigrants. Moreover, the differences between immigrants and non-immigrants were of similar magnitude across cohorts. This suggests that the attachment styles of immigrants are not influenced by the host culture, and that the observed differences in attachment styles between immigrants and nonimmigrants last over time, and presumably, existed prior to emigration. Finally, we found that secure attachment was a stronger predictor of psychological health in the emigrant sample than in the in-country sample. In sum, evidence for a migrant personality has been found. This personality, as the results suggest, is functional for immigrants.