Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuronal Functions of the Novel Serine/Threonine Kinase Ndr2*

We have identified a novel member of the Ndr subfamily of serine/threonine protein kinases, Ndr2, as a gene product that is induced in the mouse amygdala during fear memory consolidation and examined a possible function of this kinase in neural differentiation. Expression of Ndr2 mRNA was detected in various cortical and subcortical brain regions, as well as non-neuronal tissues. Its expression in the amygdala was increased 6 h after Pavlovian fear conditioning training and returned to control levels within 24 h. To study intracellular localization and functions of Ndr2, EGFP::Ndr2 fusion proteins were expressed in rat pheochromocytoma (PC12) cells and acutely isolated cortical neurons, thereby revealing an association of Ndr2 with the actin cytoskeleton in somata, neurites and filopodia, in spines and at sites of cell contact. Co-precipitation and pull-down experiments support this finding. Evidence for an involvement of Ndr2 in actin-mediated cellular functions further comes from the observation of decreased cell spreading and changes in neurite outgrowth that were associated with protein serine phosphorylation in transfected PC12 cells. Together, our data suggest that Ndr2 is an interesting candidate gene for the regulation of structural processes in differentiating and mature neuronal cells.
P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers.

The objective of this study was to investigate the mechanisms by which berberine is transported in the secretory and absorptive directions across Caco-2 cell monolayers. The basolateral-to-apical (B-A) flux was 30-fold greater than the apical-to-basolateral flux and temperature dependent (i.e., drastic decrease at 4 degrees C compared with 37 degrees C). The above results suggest the involvement of a carrier-mediated active transport mechanism for the B-A transport of berberine. However, no significant concentration dependency for the permeability (P(app)) of berberine was observed for B-A transport over a concentration range of 5-300 microM, indicating that the K(m) value of berberine for the carrier system is greater than 300 microM. Well-documented P-glycoprotein (P-gp) substrates such as verapamil, daunomycin, and rhodamine123 inhibited the B-A flux of berberine, whereas tetraethylammonium and taurocholate did not, suggesting that P-gp is involved in the transport. For the case of daunomycin, the B-A flux, but not the apical-to-basolateral flux, was significantly increased after pretreatment of the cell monolayers with berberine. In addition, the uptake of 1 microM daunomycin into Caco-2 cells was decreased as a result of this pretreatment. These results suggest that the repeated administration of berberine may up-regulate P-gp functions in Caco-2 cells. If this occurs in the gastrointestinal epithelial cells, the repeated administration of berberine may reduce the gastrointestinal absorption of P-gp substrates including chemotherapeutic agents such as daunomycin.
Progressive photon mapping: A probabilistic approach

In this article we present a novel formulation of progressive photon mapping. Similar to the original progressive photon mapping algorithm, our approach is capable of computing global illumination solutions without bias in the limit, and it uses only a constant amount of memory. It produces high-quality results in situations that are difficult for most other algorithms, such as scenes with realistic light fixtures where the light sources are completely enclosed by refractive material. Our new formulation is based on a probabilistic derivation. The key property of our approach is that it does not require the maintenance of local photon statistics. In addition, our derivation allows for arbitrary kernels in the radiance estimate and includes stochastic ray tracing algorithms. Finally, our approach is readily applicable to volumetric photon mapping. We compare our algorithm to previous progressive photon mapping approaches and show that we achieve the same convergence to unbiased results, even without local photon statistics.
DNA methylation assay for colorectal carcinoma

Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involvesAPC/β-catenin characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions inDNA mismatch repair genes. Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis. Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction (qPCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool qPCR methylation test may also be an enhanced tool for CRC and adenoma screening.
In Vitro Antifungal Susceptibilities of Sporothrix schenckii in Two Growth Phases

ABSTRACT We have determined the antifungal susceptibilities of 34 clinical isolates of the dimorphic fungus Sporothrix schenckii to 11 drugs using a microdilution method. In general, the type of growth phase (mycelial or yeast) and the temperature of incubation (30 or 35°C) exerted a significant influence on the MICs.
Real-Time PCR as a Prognostic Tool for Human Congenital Toxoplasmosis

ABSTRACT Real-time PCR (qPCR) was positive in 72/150 (48%) blood samples of newborns with congenital toxoplasmosis. Among infants with active retinochoroiditis, 68% had positive qPCR results, while positivity was 29% (P = 0.009) in the absence of ocular involvement. Positive qPCR was associated with the presence of retinochoroidal lesions, with an odds ratio of 2.8.
Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects.

AIM Cannabinoid receptor type 1 (CB1 ) antagonists show central side effects, whereas beneficial effects are most likely peripherally mediated. In this study, the peripherally selective CB1 antagonist TM38837 was studied in humans. METHODS This was a double-blind, randomized, placebo-controlled, crossover study. On occasions 1-4, 24 healthy subjects received 5 × 4 mg THC with TM38837 100 mg, 500 mg or placebo, or placebos only. During occasion 5, subjects received placebo TM38837 + THC with rimonabant 60 mg or placebo in parallel groups. Blood collections and pharmacodynamic (PD) effects were assessed frequently. Pharmacokinetics (PK) and PD were quantified using population PK-PD modelling. RESULTS The TM38837 plasma concentration profile was relatively flat compared with rimonabant. TM38837 showed an estimated terminal half-life of 771 h. THC induced effects on VAS feeling high, body sway and heart rate were partly antagonized by rimonabant 60 mg [-26.70% [90% confidence interval (CI) -40.9, -12.6%]; -7.10%, (90%CI -18.1, 5.3%); -7.30%, (90% CI -11.5%, -3.0%) respectively] and TM38837 500 mg [-22.10% (90% CI -34.9, -9.4%); -12.20% (90% CI -21.6%, -1.7%); -8.90% (90% CI -12.8%, -5.1%) respectively]. TM38837 100 mg had no measurable feeling high or body sway effects and limited heart rate effects. CONCLUSIONS Rimonabant showed larger effects than TM38837, but the heart rate effects were similar. TM38837 100 mg had no impact on CNS effects, suggesting that this dose does not penetrate the brain. This TM38837 dose is predicted to be at least equipotent to rimonabant with regard to metabolic disorders in rodent models. These results provide support for further development of TM38837 as a peripherally selective CB1 antagonist for indications such as metabolic disorders, with a reduced propensity for psychiatric side effects.
Maps of the Brain

We review recent developments in brain mapping and computational anatomy that have greatly expanded our ability to analyze brain structure and function. The enormous diversity of brain maps and imaging methods has spurred the development of population‐based digital brain atlases. These atlases store information on how the brain varies across age and gender, across time, in health and disease, and in large human populations. We describe how brain atlases, and the computational tools that align new datasets with them, facilitate comparison of brain data across experiments, laboratories, and from different imaging devices. The major methods are presented for the construction of probabilistic atlases, which store information on anatomic and functional variability in a population. Algorithms are reviewed that create composite brain maps and atlases based on multiple subjects. We show that group patterns of cortical organization, asymmetry, and disease‐specific trends can be resolved that may not be apparent in individual brain maps. Finally, we describe the creation of four‐dimensional (4D) maps that store information on the dynamics of brain change in development and disease. Digital atlases that correlate these maps show considerable promise in identifying general patterns of structural and functional variation in human populations, and how these features depend on demographic, genetic, cognitive, and clinical parameters. Anat Rec (New Anat) 265:37–53, 2001. © 2001 Wiley‐Liss, Inc.
Sensitization of insensitive branches of C nociceptors in human skin.

1. Eighteen cutaneous mechanosensitive C nociceptors were recorded from the peroneal nerves of healthy human subjects. Their identity was continuously monitored by intracutaneous electrical stimulation, and their activation by mechanical or transcutaneous electrical stimulation was detected by slowing of conduction velocity during the relative refractory period. 2. Mechanoreceptive fields (mRFs) mapped with suprathreshold von Frey hair stimuli covered an area of 99 +/‐ 21 mm2 (mean +/‐ S.E.M.). Two of the units had separate mRFs, with borders about 0.5‐1.5 cm apart from each other and the largest of these units had a maximal diameter of 4.5 cm. 3. Successive topical application of mustard oil and capsaicin induced expansions of mRFs by 57 +/‐ 14 mm2 in eight of fifteen units. 4. In twelve units transcutaneous electrical stimulation delivered through a pointed electrode was used for mapping the electroreceptive fields (eRFs). The borders of the eRFs and the mRFs were identical for two of twelve units only. In the other ten units additional mechano‐insensitive areas (55 +/‐ 22 mm2) were detected from which transcutaneous electrical stimuli could activate the respective unit. 5. Application of mustard oil and capsaicin to these mechano‐insensitive areas sensitized five of eight units to mechanical stimuli. In these cases the mRF after sensitization exactly corresponded to the eRF. 6. It is concluded that there are insensitive branches in human mechanosensitive cutaneous C nociceptors that can be detected by transcutaneous electrical stimulation and sensitized by topical application of chemical irritants. Activation of those branches in the course of inflammatory processes may contribute to spatial summation at central synapses and hence to hyperalgesia.
Chronic pain, activity restriction and flourishing mental health.

BACKGROUND According to the activity restriction (AR) model, a potential explanation for the impact of chronic pain on mental illness is that pain contributes to depression by limiting usual activities. This study uses a measure of mental health (flourishing), rather than mental illness to examine associations between pain and activity restrictions. DATA AND METHODS Data from the 2011/2012 Canadian Community Health Survey were used to study the relationship between pain intensity, pain-related activity prevention, and flourishing mental health in people aged 18 or older. Multivariate logistic regression was used in a sample of 26,429 people with chronic pain to identify significant relationships, while adjusting for potential confounders. RESULTS In 2011/2012, an estimated 6 million Canadians aged 18 or older (22%) reported chronic pain. They were less likely to be in flourishing mental health than were people without chronic pain (69% versus 79%). The prevalence of flourishing mental health declined as pain intensity and the number of activities prevented because of pain increased. Pain intensity and pain-related activity prevention were each independently associated with flourishing mental health, even when socio-demographic and health factors were taken into account. Pain-related activity prevention partially mediated the association between pain intensity and flourishing mental health. INTERPRETATION The results of this study support the AR model and highlight the importance of both pain intensity and activity restriction in relation to flourishing mental health.
Epidemiologic surveillance in the control of infectious disease.

[Biographical sketch: Karel RaSka was born in StraSeft, Czechoslovakia, in 1909. He received a degree in medicine and was trained in pathology and microbiology at the Charles University in Prague. Between 1939 and 1952, he was Director of the Division of Microbiology and Epidemiology of the State Institute of Public Health of Czechoslovakia and was responsible for the control of communicable diseases. When the Research Institute of Epidemiology and Microbiology was founded, he was its director from 1952 to 1963. Dr. Raska was professor of microbiology and later of epidemiology at the Charles University and established himself as an outstanding figure in the study of gram-negative bacilli, streptococci, and in the field of theoretical and practical epidemiology. He then became Director of the Division of Communicable Diseases at the World Health Organization in Geneva and served in this post with distinction for many years. Since the early 1970s, he and his wife, Helena RaSkova (also a physician and professor of pharmacology at the Charles University and a notable contributor to the understanding of microbial toxin) have been working in the area of veterinary research. They found that the farmers were greatly distressed by the high mortality of calves in one region; the calves were dying of a diarrheal disorder. The RaSkas immediately went to work teaching the farmers how to use a modified, balanced solution of salt and glucose of the type that was used in the treatment of human cholera and severe diarrhea in humans. Mortality in the calves was reduced from 50%o to <5%. It is not widely appreciated that the successful program to eradicate smallpox worldwide began while Karel Ra~ka was at the World Health Organization. It was by his efforts that the campaign was reoriented from one based on mass vaccination alone to an approach that integrated case
Central nervous system involvement at first relapse in patients with acute myeloid leukemia

The risk factors for and incidence of central nervous system involvement at first relapse in adult patients with acute myeloid leukemia have not been established. This single-center study analyzed the prognostic factors for and cumulative incidence of meningeal relapse in 458 adult patients achieving complete remission. Before 1990, patients received old chemotherapy approaches without stem cell transplantation that often included prophylactic intrathecal chemotherapy. Since 1990, modern protocols included stem cell transplantation without intrathecal prophylaxis. Meningeal relapse occurred in 6 patients (overall 5-year cumulative incidence 1.3%). The 5-year cumulative incidence of meningeal relapse in patients treated with old and modern protocols were 3.9% and 0.3%, respectively. Univariate and multivariate analyses showed that the chemotherapy approach was the main prognostic factor for central nervous system relapse (P=0.02). This study shows an extremely low incidence of meningeal relapse in adult patients with acute myeloid leukemia treated with modern protocols including stem cell transplantation without intrathecal prophylaxis.
Interrelated influence of light and Ni on Trichodesmium growth

Our previous laboratory study revealed that insufficient Ni supply can limit nitrogen fixation in Trichodesmium, a primary diazotrophic phytoplankton in the tropical and subtropical oceans. Here we show that light intensity and Ni availability interrelate to influence Trichodesmium growth. Trichodesmium growth is severely inhibited under high light (670 μE m–2 s–1) and insufficient Ni condition. On the contrary, the sufficient supply of Ni in seawater can sustain the growth of Trichodesmium under either high or low light conditions. We also observed elevated intracellular Ni uptake in Trichodesmium grown under relatively high light condition, supporting that the Ni requirement is used for removing superoxide generated through photosynthetic electron transport. This study shows that light saturation condition for Trichodesmium growth is Ni concentration dependent. This finding may exhibit implications for interpreting temporal and spatial distributions and activities of Trichodesmium in both modern and ancient oceans when light intensity and Ni concentrations have significantly varied.
Changes induced by aluminum stress in the organic acid content of maize seedlings: The crucial role of exogenous citrate in enhancing seedling growth

We have studied the effect of Al on growth and morphology of maize seedlings (Zea mays L.), the changes in organic acid content as well as the role of application of exogenous citrate in enhancing the Al tolerance. Al treatment induced inhibition of root growth, causing morphological symptoms of Al toxicity. Al decreased significantly the malate content in roots compared to control plants. However, the citrate and total organic acids did not show any change, indicating that one mechanism underlying plant defense may involve the maintenance a normal levels of organic acids in roots. The succinate content increased in roots at 1000 µmol L−1 Al, while that of lactate decreased. However, 500 and 1000 µmol L−1 Al significantly increased the total organic acid in shoots, due to an increase in the succinate and malate contents. By contrast, the citrate and lactate levels decreased at 250 and 500 µmol L−1 Al. To investigate the role of citrate in enhancing the plant growth, citrate was supplied to nutrient medium containing 500 µmol L−1 Al at different Al:Citrate ratios (1:1, 1:2 and 1:3). The addition of citrate in the nutrient solution resulted in an alleviation of Al toxicity, with the maximal effect obtained at Al:Citrate ratio of 1:2. These data provide evidence that in maize, the organic acids, mainly citrate play an important role in enabling the plant to tolerate elevated exposure to Al concentration.
Controller design for a single-phase two-cell multilevel cascade H-bridge converter

In this paper is studied the single-phase two-cell multilevel cascade H-bridge power converter connected to the grid, acting as a synchronous rectifier. The power exchange process between the cells of the converter and the grid is analyzed. Based on this analysis and on the power converter model the stages of the controller design process are shown. A new controller for the cascade power converter is proposed, achieving the regulation of each DC-Link capacitor voltage towards its reference. The proposed controller includes a repetitive scheme in the current tracking loop, providing low current harmonic content and almost unity power factor. Simulation results have been carried out in a 10 kVA single-phase two-cell multilevel cascade H-bridge power converter model to illustrate the good performance of the proposed controller.
Glucose-1-Phosphate Transport into Protoplasts and Chloroplasts from Leaves of Arabidopsis1

Almost all glucosyl transfer reactions rely on glucose-1-phosphate (Glc-1-P) that either immediately acts as glucosyl donor or as substrate for the synthesis of the more widely used Glc dinucleotides, ADPglucose or UDPglucose. In this communication, we have analyzed two Glc-1-P-related processes: the carbon flux from externally supplied Glc-1-P to starch by either mesophyll protoplasts or intact chloroplasts from Arabidopsis (Arabidopsis thaliana). When intact protoplasts or chloroplasts are incubated with [U-14C]Glc-1-P, starch is rapidly labeled. Incorporation into starch is unaffected by the addition of unlabeled Glc-6-P or Glc, indicating a selective flux from Glc-1-P to starch. However, illuminated protoplasts incorporate less 14C into starch when unlabeled bicarbonate is supplied in addition to the 14C-labeled Glc-1-P. Mesophyll protoplasts incubated with [U-14C]Glc-1-P incorporate 14C into the plastidial pool of adenosine diphosphoglucose. Protoplasts prepared from leaves of mutants of Arabidopsis that lack either the plastidial phosphorylase or the phosphoglucomutase isozyme incorporate 14C derived from external Glc-1-P into starch, but incorporation into starch is insignificant when protoplasts from a mutant possessing a highly reduced ADPglucose pyrophosphorylase activity are studied. Thus, the path of assimilatory starch biosynthesis initiated by extraplastidial Glc-1-P leads to the plastidial pool of adenosine diphosphoglucose, and at this intermediate it is fused with the Calvin cycle-driven route. Mutants lacking the plastidial phosphoglucomutase contain a small yet significant amount of transitory starch.
DNA Methylation in Circulating Tumour DNA as a Biomarker for Cancer

Free circulating DNA, which is thought to be derived from the primary tumour, can be detected in the blood of patients with cancer. Detection of genetic and epigenetic alteration in this tumour DNA offers a potential source of development of prognostic and predictive biomarkers for cancer. One such change is DNA methylation of the promotor region of tumour suppressor genes. This causes down regulation of tumour suppressor gene expression, a frequent event in carcinogenesis. Hypermethylation of the promotor region of a number of genes has been detected in many tumour types and more recently these changes have been detected in circulating tumour DNA. This review will summarise the literature detailing DNA methylation in circulating tumour DNA and discuss some of the current controversies and technical challenges facing its use as a potential biomarker for cancer.
Heckscher-Ohlin Business Cycles 1

This paper introduces Heckscher-Ohlin trade features into a two-country dynamic stochastic general equilibrium model, and studies the international transmission of productivity shocks through trade in goods. This framework improves upon existing international real business cycle models in that it generates business cycle properties comparable with the empirical evidence regarding the terms of trade and the trade balance.