Miracle-dz/UniFAR-FTUs huggingface dataset:
Neocortical arealization: Evolution, mechanisms, and open questions

The mammalian neocortex is a structure with no equals in the vertebrates and is the seat of the highest cerebral functions, such as thoughts and consciousness. It is radially organized into six layers and tangentially subdivided into functional areas deputed to the elaboration of sensory information, association between different stimuli, and selection and triggering of voluntary movements. The process subdividing the neocortical field into several functional areas is called “arealization”. Each area has its own cytoarchitecture, connectivity, and peculiar functions. In the last century, several neuroscientists have investigated areal structure and the mechanisms that have led during evolution to the rising of the neocortex and its organization. The extreme conservation in the positioning and wiring of neocortical areas among different mammalian families suggests a conserved genetic program orchestrating neocortical patterning. However, the impressive plasticity of the neocortex, which is able to rewire and reorganize areal structures and connectivity after impairments of sensory pathways, argues for a more complex scenario. Indeed, even if genetics and molecular biology helped in identifying several genes involved in the arealization process, the logic underlying the neocortical bauplan is still beyond our comprehension. In this review, we will introduce the present knowledge and hypotheses on the ontogenesis and evolution of neocortical areas. Then, we will focus our attention on some open issues, which are still unresolved, and discuss some recent studies that might open new directions to be explored in the next few years. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 73: 411–447, 2013.
Factors attributed to the higher in-hospital mortality of ST elevation myocardial infarction patients admitted during off-hour in comparison with those during regular hour

Background In-hospital mortality of patients with ST elevation myocardial infarction (STEMI) admitted during off-hour was reported higher than those admitted during regular hour, but which factors cause the difference remains largely unknown though the difference in medical resources was often accused. Methods and results This registry-based study recruited 7456 STEMI patients prospectively from 99 level two hospitals across China. Generalized linear mixed models were applied to quantify the risk of in-hospital death attributed to admission time and the explainers of its change, accounting for the clustering of patients within hospitals. There were 45.2% patients admitted during regular hour and 54.8% during off-hour. In-hospital mortality was 7.0% for patients admitted during regular hour and 8.3% for those during off-hour (p<0.05). Generalized linear mixed models adjusting for age, gender and education showed that patients’ disease severity at admission and medical treatments received after admission could explain the risk difference attributed to admission time by 55% and 20%, respectively. After all factors accounted, the residual relative risk difference left only 6% (adjusted OR = 0.94) and became no longer significant. Conclusions The regular-and-off-hour mortality difference exists among STEMI patients in Chinese level two hospitals, which could be attributed primarily to disease severity at admission and secondly to the poorer medical treatments. These results call for public attention to the more severity of STEMI patients admitted during off-hour in addition to improving medical resources for STEMI at off-hour.
ST elevation myocardial infarction in a young patientafter ingestion of caffeinated energy drink and ecstasy.

BACKGROUND Caffeinated energy drinks are widely used worldwide. They are associated with a variety of adverse effects and are of concern to health authorities, yet there is still scarce information about their adverse effects and inadequate awareness among medical personnel. METHODS Case description and discussion of a patient presenting to the emergency room after overdose of energy drinks in combination with 3,4-methylenedioxymethamphetamine (MDMA). RESULTS Despite best medical efforts, the patient died of fatal cardiac arrhythmias. There is a paucity of information about adverse effects of energy drinks. CONCLUSION Although energy drinks are widely used, there is a lack of awareness in the population and medical staff about their hazards.
Impact Des Structures Fiscales Sur La Croissance Economique Au Congo-Brazzaville

This article proposes to make from Congolese data an empirical evaluation of the impact of tax structures on economic growth. It is based on the effects of state transfers to businesses and on the distinction between personal income taxes, corporate taxes and taxes on goods and services. The results obtained from Dickey and Fuller's model show that, in the long term, personal income taxes, taxes on goods and services, total state revenues, state transfers to enterprises and gross fixed capital formation affect economic growth. In the short term, corporate taxes, revenues and transfers from the state to companies exert an influence on this growth. On the other hand, long-term and short-term results show that government revenues and transfers affect economic growth. These results made it possible to identify the limits of the economic policies implemented in Congo-Brazzaville.
Role of yessotoxin in calcium and cAMP‐crosstalks in primary and K‐562 human lymphocytes: The effect is mediated by Anchor kinase a mitochondrial proteins

Yessotoxin (YTX) is a marine polyether toxin previously described as a phosphodiesterase (PDE) activator in fresh human lymphocytes. This toxin induces a decrease of adenosine 3′,5′‐cyclic monophosphate (cAMP) levels in fresh human lymphocytes in a medium with calcium (Ca2+), whereas the contrary effect has been observed in a Ca2+‐free medium. In the present article, the effect of YTX in K‐562 lymphocytes cell line has been analysed. Surprisingly, results obtained in K‐562 cell line are completely opposite than in fresh human lymphocytes, since in K‐562 cells YTX induces an increase of cAMP levels. YTX cytotoxicity was also studied in both K‐562 cell line and fresh human lymphocytes. Results demonstrate that YTX does not modify fresh human lymphocytes viability, whereas in K‐562 cells, YTX has a highly cytotoxic effect. It has been described in a previous study that YTX induces a small cytosolic Ca2+ increase in fresh human lymphocytes but no effect was observed on Ca2+ pools depletion in these cells. However, our results show that, in K‐562 cells, YTX has no effect on cytosolic Ca2+ levels in a medium with Ca2+ and induces an increase on Ca2+ pools depletion followed by a Ca2+ influx. As far as Ca2+ modulation is concerned these results demonstrate that YTX has a clear opposite effect in tumoural and fresh human lymphocytes. In addition, intracellular Ca2+ reservoirs affected by YTX are different than thapsigargin‐sensible pools. Furthermore, YTX‐dependent Ca2+ pools depletion was abolished by cAMP analogue (dibutyryl cAMP), phosphodiesterase‐4 (PDE4) inhibitor (rolipram), protein kinase A inhibitor (H89) and oxidative phosphorylation uncoupler carbonyl cyanide p‐(trifluoromethoxy) (FCCP) treatments. This evidences the crosstalks between Ca2+, YTX and cAMP pathways. Also, results obtain demonstrate that YTX‐dependent Ca2+ influx was only abolished by FCCP pre‐treatment, which indicates a link between YTX and mitochondria in K‐562 cell line. Cytosolic expression of A‐kinase anchor proteins (AKAPs), the proteins which integrates phosphodiesterases (PDEs) and PKA to the mitochondria, was determined in both cell models. On the one hand, in human fresh lymphocytes, YTX increases AKAP149 cytosolic expression. This fact is accompanied with a decrease in cAMP levels, and therefore PDEs activation, which finally leads to cell survival. On the other hand, in tumoural lymphocytes, YTX has an opposite effect since decreases AKAP149 cytosolic expression and increase cAMP levels which leads to cell death. This is the first time that YTX and mitochondrial AKAPs proteins relationship is characterised. J. Cell. Biochem. 113: 3752–3761, 2012. © 2012 Wiley Periodicals, Inc.
An increase of VEGF plasma levels is associated with restenosis of drug-eluting stents.

AIMS Drug-eluting stents (DES) reduce late lumen loss compared to bare metal stents but were not able to eradicate in-stent restenosis (ISR) fully. Vascular endothelial growth factor (VEGF) may inhibit late lumen loss through accelerated reendothelialisation, but may also promote neointima formation by proinflammatory effects. The aim of this study was to evaluate whether endogenous plasma levels of VEGF are associated with development of ISR after implantation of DES. METHODS AND RESULTS We studied 85 patients who were treated with 159 DES. VEGF plasma levels were determined before and 24 hours after PCI. During the eight-month follow-up period, two patients (2.4%) died of cardiovascular causes and 12 patients (14.5% of patients, 7.6% of stents) developed angiographic ISR. Basal VEGF plasma levels were not different in patients with and without ISR at follow-up. In contrast to patients without ISR, VEGF increased significantly upon PCI in patients with ISR (p<0.005). Patients with a decrease of VEGF after PCI had a restenosis rate of 2.4% compared to a restenosis rate of 26.2% in patients with an increase of VEGF after the procedure (p<0.05). This was independent from clinical and angiographic risk factors. CONCLUSIONS Basal plasma levels of VEGF are not associated with the development of ISR. However, an increase of VEGF after PCI is associated with a dramatically increased ISR rate after implantation of DES.
Measuring the effect of influenza A(H1N1)pdm09: the epidemiological experience in the West Midlands, England during the ‘containment’ phase

SUMMARY The West Midlands was the first English region to report sustained community transmission during the ‘containment’ phase of the influenza A(H1N1)pdm09 pandemic in England. To describe the epidemiological experience in the region, West Midlands and national datasets containing laboratory-confirmed A(H1N1)pdm09 virus cases in the region during the ‘containment’ phase were analysed. The region accounts for about 10·5% of England's population, but reported about 42% of all laboratory-confirmed cases. Altogether 3063 cases were reported, with an incidence rate of 56/100 000 population. School-associated cases accounted for 25% of cases. Those aged <20 years, South Asian ethnic groups, and residents of urban and socioeconomically deprived areas were disproportionately affected. Imported cases accounted for 1% of known exposures. Regional R 0 central estimates between 1·41 and 1·43 were obtained. The West Midlands experience suggests that interpretation of transmission rates may be affected by complex interactions within and between sub-populations in the region.
Induced hypothermia as a new approach to lung rest for the acutely injured lung*

Objective:To investigate whether low-frequency ventilation during hypothermia could attenuate lung injury associated with endotoxin and mechanical ventilation. Design:Experimental animal study. Setting:University-affiliated animal laboratory. Subjects:Forty-eight Sprague–Dawley rats. Interventions:Lipopolysaccharide was administered to rats intratracheally to induce acute lung injury. After 1 hr of this treatment, animals were assigned to normothermia-only (NO, rectal temperature 37°C, ventilatory frequency 90/min), normothermia-lung rest (NR, 37°C, 45/min), hypothermia-only (HO, 27°C, 90/min), or hypothermia-lung rest (HR, 27°C, 45/min). After 1 hr of injurious ventilation, the lungs of the rats were removed for bronchoalveolar lavage and histologic examination. Measurements and Main Results:Compared with the normothermia groups (NO, NR), the neutrophil counts (per milliliter) (NO, 7708 ± 5704; NR, 10,479 ± 11,152; HO, 1638 ± 955; HR, 805 ± 591) and interleukin-1&bgr; levels (pg/mL) (1180 ± 439, 1081 ± 652, 620 ± 426, 420 ± 182, respectively) in the bronchoalveolar lavage fluid, the wet-to-dry lung weight ratios (6.0 ± 0.4, 5.7 ± 0.4, 5.6 ± 0.2, 5.2 ± 0.2, respectively), and histologic acute lung injury scores (8.3 ± 2.7, 10.4 ± 3.1, 3.5 ± 2.1, 3.1 ± 2.2, respectively) of the hypothermia groups (HO, HR) were lower (all p < .001). Compared with the HO group, the neutrophil counts and protein content (HO, 1367 ± 490 &mgr;g/mL vs. HR, 831 ± 369 &mgr;g/mL) in the bronchoalveolar lavage fluid, the serum lactate dehydrogenase levels (units/mL) (9.1 ± 3.6 vs. 5.3 ± 1.5), and the wet-to-dry lung weight ratios of the HR group were lower (all p < .05). Conclusions:Reduction of ventilatory frequency in conjunction with hypothermia attenuated many variables of acute lung injury in rats. Use of hypothermia could be exploited as a new approach to lung rest for the ventilatory management of the acutely injured lung.
[Effect of dimethyl diphenyl bicarboxylate (DDB) on 9-amino-1,2,3,4-tetrahydroacridine-induced hepatotoxicity in mice].

AIM To establish an acute model of THA-induced hepatotoxicity in mice, and observe the effects of DDB on THA-induced liver damage. METHODS After a single oral dose of THA (56 mg.kg-1), body temperatures, liver MDA content and serum ALT were measured within 12 h. The activities of mice brain acetylcholinesterase, liver microsomal 7-ethoxyresorufin deethylase, uridine-5'-diphosphoglucuronic transferase, and mitochondria potential change were also observed. RESULTS The alteration of mice body temperature, and the elevation of serum ALT, liver MDA content, and mitochondria potential induced by THA were significantly inhibited by DDB pretreatment. The microsomal 7-ethoxyresorufin deethylase activity was induced by DDB too. On the other hand, The inhibiting effects of THA on mice hippocampus and cortex acetylcholinesterase in vitro and in vivo were not influenced by DDB treatment. CONCLUSION The toxic effect of THA on mice liver was significantly reduced by DDB. These results demonstrate that the protective action of DDB may attribute to its regulation on enzymes involved in THA metabolism, and its protective effect against mitochondria injury caused by THA. Therefore, DDB may be a potential liverprotector against THA-induced hepatotoxicity during dementia therapy.
Perspectives on deciphering mechanisms underlying plant heat stress response and thermotolerance

Global warming is a major threat for agriculture and food safety and in many cases the negative effects are already apparent. The current challenge of basic and applied plant science is to decipher the molecular mechanisms of heat stress response (HSR) and thermotolerance in detail and use this information to identify genotypes that will withstand unfavorable environmental conditions. Nowadays X-omics approaches complement the findings of previous targeted studies and highlight the complexity of HSR mechanisms giving information for so far unrecognized genes, proteins and metabolites as potential key players of thermotolerance. Even more, roles of epigenetic mechanisms and the involvement of small RNAs in thermotolerance are currently emerging and thus open new directions of yet unexplored areas of plant HSR. In parallel it is emerging that although the whole plant is vulnerable to heat, specific organs are particularly sensitive to elevated temperatures. This has redirected research from the vegetative to generative tissues. The sexual reproduction phase is considered as the most sensitive to heat and specifically pollen exhibits the highest sensitivity and frequently an elevation of the temperature just a few degrees above the optimum during pollen development can have detrimental effects for crop production. Compared to our knowledge on HSR of vegetative tissues, the information on pollen is still scarce. Nowadays, several techniques for high-throughput X-omics approaches provide major tools to explore the principles of pollen HSR and thermotolerance mechanisms in specific genotypes. The collection of such information will provide an excellent support for improvement of breeding programs to facilitate the development of tolerant cultivars. The review aims at describing the current knowledge of thermotolerance mechanisms and the technical advances which will foster new insights into this process.
Impact of dabigatran on a large panel of routine or specific coagulation assays

Summary Due to low bioavailability and high inter-individual variability, monitoring of dabigatran may be required in specific situations to prevent the risk of bleedings or thrombosis. The aim of the study was to determine which coagulation assay(s) could be used to assess the impact of dabig-atran on secondary haemostasis. Dabigatran was spiked at concentrations ranging from 4.7 ng/ml to 943.0 ng/ml in pooled citrated human platelet-poor plasma. The following clotting assays were performed: prothrombin time (PT); activated partial thromboplastin time (aPTT); thrombin time (TT); ecarin clotting time (ECT); ecarin chromo-genic assay (ECA); prothrombinase-induced clotting time (PiCT); activated clotting time (ACT); Hemoclot Thrombin Inhibitor (HTI) and thrombin generation assay (TGA). A concentration-dependent prolongation of PT, dPT, and aPTT was observed with aPTT being the more sensitive test. The results varied mostly due to the clotting reagent. HTI, ECT and TGA were the most sensitive tests but are not available 24 hours a day. In addition, HTI showed a linear correlation with a good reproduci-bility. Dabigatran induced a concentration-dependent delay and inhibition of tissue factor-induced TGA. Cut-offs related with higher risk of bleedings or thrombosis were defined for each reagent of aPTT and HTI. In conclusion, aPTT could be used for the monitoring of dabigatran and as screening test for the risk of overdose. However, because of its higher sensitivity, good reproducibility, excellent linear correlation at all doses, its simplicity of use, and possibilities of automation, HTI should be considered as the gold-standard.
Prevalence of respiratory syncytial virus IgG antibodies in infants living in a rural area of Mozambique

A case control study was carried out in Manhiça (Mozambique). Serum samples were collected from infants < 1 year of age in hospital to assess the effect of serum antibodies on the incidence of respiratory syncytial virus (RSV) infection. Sera were collected from a total of 31 cases of RSV infection and paired uninfected controls matched for age and sex. Anti‐RSV antibodies were assessed by a membrane fluorescent antibody test (MFAT) for immunoglobulin G (IgG) antibodies and by a neutralizing antibody test. IgG RSV antibodies were of higher prevalence and at higher levels in the control group when compared to the infected case group (P < 0.001), indicating an important role for IgG antibodies in protection. To assess infection before recruitment, IgA RSV antibodies were also measured by MFAT. IgA RSV antibody prevalence was very low in patients and controls (0/31 and 4/31 respectively), suggesting that most of the detected IgG RSV antibody in both groups was of maternal origin. Re‐analysis of data from the subset of 27 matched, IgA RSV antibody negative infant pairs mirrored the full analysis indicating that maternal antibody has an important role in RSV protection. Similar results were obtained when neutralizing antibodies were measured and when the measurement was done against subgroup A virus strain A2, subgroup B virus strain 8/60 and a contemporary subgroup A isolate, Moz00. No significant differences in the reactivity of maternal antibodies with the three virus strains were observed. The data described below represent the first analysis of the role of maternal antibodies in reducing the risk of pediatric infection in developing countries. The results reinforce the concept of maternal vaccination for the control of RSV in very young children in whom the risk and severity of infection are the highest. J. Med. Virol. 67:616–623, 2002. © 2002 Wiley‐Liss, Inc.
How Much Information is Incorporated in Financial Asset Prices? Experimental Evidence

We propose a new estimation method and use experimental data from multiple double auction experiments in the literature to directly estimate how much information is incorporated in financial market prices. We find that public information is almost completely reflected in prices, but that surprisingly little private information—less than 50%—is incorporated in prices. Our estimates therefore suggest that while semi-strong informational efficiency is consistent with the data, financial market prices may be very far from strong-form efficiency. We compare our estimates with beliefs of economists surveyed at the Econometric Society Meetings, and find that economists and finance researchers alike expect market prices to reflect considerably more private information than what we estimated.
Clock buffer polarity assignment considering the effect of delay variations

This work addresses the problem of minimizing power/ground noise with an important design parameter, which is the delay variations on the clock tree. Without considering the effect of delay variations on the polarity assignment, the resulting statistical clock skew may lead to a high probability of skew violation, which causes a low yield of design. Given distributions on the delay of each type of buffering elements and the interconnect delay from the clock source to every flip-flop with spatial delay correlations, and the clock skew and yield constraints, we solve the problem of assigning polarity to each sink buffer (i.e., assigning a buffering type) so that the power/ground noise is minimized while satisfying the yield and clock skew constraints. Specifically, we solve the problem in two steps where in step 1, for each pair of sinks a set of feasible combination(s) of polarities to the sinks that do not violate the yield constraint as well as the clock skew constraint is extracted, and in step 2, a stepwise greedy method is applied to determine the polarities to sinks from the feasible sets obtained in step 1 to minimize the power/ground noise. Through experiments with ISCAS89 benchmark circuits, it is shown that our proposed approach is able to improve yield by 6.7% on average even with 4.3% less power and 4.4% less ground noises over the results by the conventional polarity assignment approach which does not consider the delay variations.
Stochasticity and Robustness in Bi-Stable Systems

The genetic bi-stable switch (toggle switch) consists of two genes which repress one another through their synthesised proteins. In the stochastic bi-stable case, the toggle switch exhibits noise induced flips. Using simulation based techniques, we identified three methods for reducing the random flipping probability, namely: (i) increasing the system size, (ii) increasing the synthesis rate, and (iii) increasing the Hill coefficient. Our heat-maps showed that for large parts of parameter space the toggle switch displays extremely low noise induced flipping probability, and consequently high robustness. We also analysed the noise analytically. The area of validity of the analytical approach was found to be constrained to low Hill coefficients and high synthesis rate (both conditions within biological realistic parameters). Most importantly, we observed that increasing the synthesis rate is more efficient in reducing the noise compared to the increase in system size, for systems affected by negative feedback.