Miracle-dz/UniFAR-FTUs huggingface dataset:
Low level of microsatellite instability in paediatric malignant astrocytomas

Aim: Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas. Methods: We screened a cohort of 126 high‐grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins. Results: We identified low level of MSI (MSI‐L) in four of 126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular profile associated with MSI‐L positive tumours, we performed immunohistochemistry for protein expression of hMSH6 and p53 as well as mutational analysis of the K‐ras gene. In MSI‐L paediatric malignant astrocytic tumours we detected retained nuclear expression of hMSH6 protein and strong nuclear accumulation of p53 protein indicating possible mutations of TP53. There was no correlation between K‐ras mutational status and frequency of MSI in this patient population. Conclusion: Our results suggest that the MSI‐L phenotype is associated with p53 accumulation and/or mutations. However, this represents only a small subgroup of paediatric gliomas with possible distinct biological features, and the deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of the majority of paediatric malignant astrocytomas.
Outbreak of tuberculosis caused by Mycobacterium bovis in golden Guernsey goats in Great Britain

An outbreak of caprine tuberculosis caused by Mycobacterium bovis was disclosed in June 2008, affecting goats of the golden Guernsey breed kept on 10 separate smallholdings in south-west Wales and the west of England. Following the initial diagnosis at postmortem examination, 30 goats that reacted positively to the single intradermal comparative cervical tuberculin (SICCT) test, together with five in-contact animals, were euthanased and subjected to postmortem examination and mycobacterial culture. Spoligotyping and variable number tandem repeat analysis of isolates showed that they were all of the same genotype, endemic to south-west Wales. Retrospective movement tracings identified a goat herd in south-west Wales, by then completely dispersed, as the probable common source of infection. There was a perfect correlation between the SICCT test and culture results in all slaughtered goats. Grossly visible tubercular lesions were observed at postmortem examination in all but one reactor.
Low-stage ovarian clear cell carcinoma: population-based outcomes in British Columbia, Canada, with evidence for a survival benefit as a result of irradiation.

PURPOSE To evaluate the population-based outcomes of stage I and II ovarian clear cell carcinoma (OCCC) in a North American population treated with carboplatin/paclitaxel and abdominopelvic irradiation. PATIENTS AND METHODS Retrospective analysis was performed of 241 patients referred in the carboplatin/paclitaxel era. Irradiation was to be used with a few defined exceptions. However, because of differing beliefs as to its effectiveness, its use was consistently avoided by specific oncologists, allowing the opportunity to study its possible effect on disease-free survival (DFS) in these concurrent cohorts. RESULTS Five- and 10-year DFS rates were 84% and 70% for stage IA/B; 67% and 57% for stage IC; and 49% and 44% for stage II, respectively. Five- and 10-year DFS rates for those with stage IC disease based purely on rupture were similar to rates for patients with stage IA/B, at 92% and 71%, respectively. The remaining patients with stage IC had 48% 5- and 10-year DFS. Multivariate analysis using a decision tree identified positive cytology as the most important factor (72% relapse rate if positive and 27% if negative or unknown). If, in addition, the capsule surface was involved, then the relapse rate was 93%. Irradiation had no discernible survival benefit for patients with stage IA and IC (rupture alone), whereas for the remainder of patients with stage IC and stage II, it improved DFS by 20% at 5 years (relative risk, 0.5); the benefit was most evident in the cytologically negative/unknown group. CONCLUSION DFS is similar in this North American population with early OCCC to the DFS reported in Asia. A potential benefit from irradiation was evident in a subset.
Analysis on Third-Degree Price Discrimination in Oligopoly Market Based on Dynamic Game Theory

Equilibrium output,equilibrium price and equilibrium total revenue in the case of implementing third-degree price discrimination and unified pricing were analyzed under the condition of two oligopoly enterprises with 2 sub markets by complete information dynamic game method,and the relationship between the three indexes of the two cases were studied.The results showed that,under the condition of linear demand functions of the two sub markets,the equilibrium output of unified pricing was equal to the equilibrium output of discriminative pricing;the equilibrium price of unified pricing was the weighted average of the equilibrium prices of two sub markets with discriminative pricing;the equilibrium total revenue of unified pricing was less than the equilibrium total revenue of discriminative pricing.
Involvement of medial prefrontal cortex in emotion during feedback presentation

It has been suggested that the posterior medial prefrontal cortex (pMPFC) implements cognitive functions involved during negative feedback processing. It has also been suggested that the presentation of the feedback elicits emotional processes. This functional MRI study examined whether pMPFC was associated with the emotional component in feedback processing. Participants were exposed to feedback while performing a version of a motion prediction task. The pMPFC was activated during negative feedback presentation and emotion-related activity was extracted from the pMPFC activation through parametric imaging analysis. It was found that the emotional pMPFC activity was greater in participants who scored higher on depressive mood scales. The results suggest that pMPFC also implements feedback-related emotional functions, which individually vary depending on depressive moods.
Earnings Inequality in Germany and Its Implications

Abstract The current paper discusses the evolution of earnings inequality in Germany with an eye to its potential lessons for China. Inequality is assessed from two different perspectives: the distribution of annual earnings, and the distributionof lifetime earnings. This paper proposes to implement closer monitoring of lifetime earnings and take a proactive stance in the formation of the wage-bargaining regime.
Spinocerebellar Ataxia Type 6 Protein Aggregates Cause Deficits in Motor Learning and Cerebellar Plasticity

Spinocerebellar ataxia type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming subunits of P/Q-type Ca2+ channels (Cav2.1) and is characterized by CT protein aggregates found in cerebellar Purkinje cells (PCs). One hypothesis regarding SCA6 disease is that a CT fragment of the Cav2.1 channel, which is detected specifically in cytosolic and nuclear fractions in SCA6 patients, is associated with the SCA6 pathogenesis. To test this hypothesis, we expressed P/Q-type channel protein fragments from two different human CT splice variants, as predicted from SCA6 patients, in PCs of mice using viral and transgenic approaches. These splice variants represent a short (CT-short without polyQs) and a long (CT-long with 27 polyQs) CT fragment. Our results show that the different splice variants of the CTs differentially distribute within PCs, i.e., the short CTs reveal predominantly nuclear inclusions, whereas the long CTs prominently reveal both nuclear and cytoplasmic aggregates. Postnatal expression of CTs in PCs in mice reveals that only CT-long causes SCA6-like symptoms, i.e., deficits in eyeblink conditioning (EBC), ataxia, and PC degeneration. The physiological phenotypes associated specifically with the long CT fragment can be explained by an impairment of LTD and LTP at the parallel fiber-to-PC synapse and alteration in spontaneous PC activity. Thus, our results suggest that the polyQ carrying the CT fragment of the P/Q-type channel is sufficient to cause SCA6 pathogenesis in mice and identifies EBC as a new diagnostic strategy to evaluate Ca2+ channel-mediated human diseases.
Maternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta

Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth.
Organization and coordinated assembly of the type III secretion export apparatus

Type III protein secretion systems are unique bacterial nanomachines with the capacity to deliver bacterial effector proteins into eukaryotic cells. These systems are critical to the biology of many pathogenic or symbiotic bacteria for insects, plants, animals, and humans. Essential components of these systems are multiprotein envelope-associated organelles known as the needle complex and a group of membrane proteins that compose the so-called export apparatus. Here, we show that components of the export apparatus associate intimately with the needle complex, forming a structure that can be visualized by cryo-electron microscopy. We also show that formation of the needle complex base is initiated at the export apparatus and that, in the absence of export apparatus components, there is a significant reduction in the levels of needle complex base assembly. Our results show a substantial coordination in the assembly of the two central elements of type III secretion machines.
A General Proof for Overlapped Multiple-Bit Scanning Multiplications

Because of recent advances in technology, multibit scanning implementations can be considered that exceed three-bit and four-bit groupings. The generalized proof for the multibit overlapped scanning multiplication is introduced, and the multiplication process is discussed. The proofs are intended to establish the correctness of the decode and the actions taken to produce the multiplication of any valid scheme proposed in the past, and to dictate the correct decode and actions taken for any overlapped s-bit scanning algorithm such that s is a natural number greater than or equal to two. The multiplication is considered to be between two fractional numbers, which are represented in two's-complement form. >
Optical center estimation for lenslet-based plenoptic cameras

Plenoptic cameras enable a variety of novel post-processing applications, including refocusing and single-shot 3D imaging. To achieve high accuracy, such applications typically require knowledge of intrinsic camera parameters. One such parameter is the location of the main lens' optical center relative to the sensor, which is required for modeling radially symmetric optical effects. We show that estimating this parameter can be achieved to an accuracy of less than half a pixel by utilising the symmetry inherent in each micro-image. Further, we show that estimating this parameter separately allows all other intrinsic camera parameters to be estimated with higher accuracy than can be achieved using a single optimization scheme, and leads to better vignetting correction than with an inaccurate optical center.
Phagocytosis of bacterial pathogens: implications in the host response.

Phagocytosis of bacterial pathogens is at the heart of the pathogenesis of infections. Pathogens have evolved a large array of strategies to escape the deleterious effect of phagocytosis by professional phagocytes among which avoiding phagocytosis, killing the phagocytes or surviving inside them are the most 'popular' solutions. Bacterial pathogens are also using induction of phagocytic entry into non-professional phagocytic cells, such as epithelial cells, as a strategy of survival and multiplication. We have taken enteroinvasive micro-organisms such as Yersinia, Shigella and Salmonella as a paradigm of the significance of phagocytosis/antiphagocytosis in the development of an infection and on the elicitation of the host response.
Development of a prescribing indicator for objective quantification of antibiotic usage in secondary care.

OBJECTIVES To compare the recognized defined daily dose per 100 bed-days (DDD/100 bed-days) measure with the defined daily dose per finished consultant episode (DDD/FCE) in a group of hospitals with a variety of medicines management strategies. To compare antibiotic usage using the above indicators in hospitals with and without electronic prescribing systems. METHODS Twelve hospitals were used in the study. Nine hospitals were selected and split into three cohorts (three high-scoring, three medium-scoring and three low-scoring) by their 2001 medicines management self-assessment scores (MMAS). An additional cohort of three electronic prescribing hospitals was included for comparison. MMAS were compared to antibiotic management scores (AMS) developed from a questionnaire relating specifically to control of antibiotics. FCEs and occupied bed-days were obtained from published statistics and statistical analyses of the DDD/100 bed-days and DDD/FCE were carried out using SPSS. RESULTS The DDD/100 bed-days varied from 81.33 to 189.37 whilst the DDD/FCE varied from 2.88 to 7.43. The two indicators showed a high degree of correlation with r=0.74. MMAS were from 9 to 22 (possible range 0-23) and the AMS from 2 to 13 (possible range 0-22). The two scores showed a high degree of correlation with r=0.74. No correlation was established between either indicator and either score. CONCLUSIONS The WHO indicator for medicines utilization, DDD/100 bed-days, exhibited the same level of conformity as that exhibited from the use of the DDD/FCE indicating that the DDD/FCE is a useful additional indicator for identifying hospitals which require further study. The MMAS can be assumed to be an accurate guide to antibiotic medicines management controls. No relationship has been found between a high degree of medicines management control and the quantity of antibiotic prescribed.
Hypoxia-Inducible Factor-1 Mediates Activation of Cultured Vascular Endothelial Cells by Inducing Multiple Angiogenic Factors

Abstract— Hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of vascular endothelial growth factor (VEGF) and other hypoxia-responsive genes. Transgenic expression of a constitutively stable HIF-1&agr; mutant increases the number of vascular vessels without vascular leakage, tissue edema, or inflammation. This study aimed to investigate the molecular basis by which HIF-1 mediates the angiogenic response to hypoxia. In primary human endothelial cells, hypoxia, desferrioxamine, or infection with Ad2/HIF-1&agr;/VP16, an adenoviral vector encoding a constitutively stable hybrid form of HIF-1&agr;, increased the mRNA and protein levels of VEGF, angiopoietin-2 (Ang-2), and angiopoietin-4 (Ang-4). Infection with Ad2/CMVEV (a control vector expressing no transgene) had no effect. Angiopoietin-1 (Ang-1) expression was not detected in human endothelial cells. Ang-4 was also induced by hypoxia or Ad2/HIF-1&agr;/VP16 in human cardiac cells, whereas Ang-1 expression remained unchanged. Recombinant Ang-4 protein protected endothelial cells against serum starvation-induced apoptosis and increased cultured endothelial cell migration and tube formation. Ad2/HIF-1&agr;/VP16 stimulated endothelial cell proliferation and tube formation. Hypoxia- or Ad2/HIF-1&agr;/VP16-induced tube formation was significantly reduced by a Tie-2 inhibitor. These results suggest that HIF-1 mediates the angiogenic response to hypoxia by upregulating the expression of multiple angiogenic factors. Ang-4 can function similarly as Ang-1 and substitute for Ang-1 to participate in hypoxia-induced angiogenesis. Activation of the angiopoietin/Tie-2 system may play a role in the ability of HIF-1 to induce hypervascularity without excessive permeability.
Direct Activation of AMP-activated Protein Kinase Stimulates Nitric-oxide Synthesis in Human Aortic Endothelial Cells*

Recent studies have indicated that endothelial nitric-oxide synthase (eNOS) is regulated by reversible phosphorylation in intact endothelial cells. AMP-activated protein kinase (AMPK) has previously been demonstrated to phosphorylate and activate eNOS at Ser-1177 in vitro, yet the function of AMPK in endothelium is poorly characterized. We therefore determined whether activation of AMPK with 5′-aminoimidazole-4-carboxamide ribonucleoside (AICAR) stimulated NO production in human aortic endothelial cells. AICAR caused the time- and dose-dependent stimulation of AMPK activity, with a concomitant increase in eNOS Ser-1177 phosphorylation and NO production. AMPK was associated with immunoprecipitates of eNOS, yet this was unaffected by increasing concentrations of AICAR. AICAR also caused the time- and dose-dependent stimulation of protein kinase B phosphorylation. To confirm that the effects of AICAR were indeed mediated by AMPK, we utilized adenovirus-mediated expression of a dominant negative AMPK mutant. Expression of dominant negative AMPK attenuated AICAR-stimulated AMPK activity, eNOS Ser-1177 phosphorylation and NO production and was without effect on AICAR-stimulated protein kinase B Ser-473 phosphorylation or NO production stimulated by insulin or A23187. These data suggest that AICAR-stimulated NO production is mediated by AMPK as a consequence of increased Ser-1177 phosphorylation of eNOS. We propose that stimuli that result in the acute activation of AMPK activity in endothelial cells stimulate NO production, at least in part due to phosphorylation and activation of eNOS. Regulation of endothelial AMPK therefore provides an additional mechanism by which local vascular tone may be controlled.
Protein tyrosine phosphorylation under capacitating conditions in porcine fresh spermatozoa and sperm cryopreserved with and without alpha tocopherol

The aim of this study was to evaluate the capacitation behaviour of fresh and α‐tocopherol frozen spermatozoa. Spermatozoa frozen with or without α‐tocopherol and fresh semen were incubated under capacitating conditions. Aliquots were collected at 0, 15, 30, 45, 60, 90, 120 and 180 min of incubation time. Parameters of semen quality were evaluated by optical microscopy and capacitation was determined by the epifluorescence chlortetracycline technique. Protein tyrosine phosphorylation was examined by Western immunoblotting. Motility, viability and intact spermatozoa were higher (P < 0.05) in fresh semen compared with frozen samples. These parameters significantly decreased, in every treatment, throughout the incubation time. Fresh semen showed a progressive increase in capacitated spermatozoa, reaching 25 ± 3% at 180 min. Cryopreserved semen had a fast increase at the beginning of incubation time (28 ± 5% at 45 min and 28 ± 3% at 30 min for samples with or without α‐tocopherol, respectively). The amount of an MW 32 kDa tyrosine‐phosphorilated protein, associated with capacitation, increased throughout incubation for fresh semen and spermatozoa cryopreserved with α‐tocopherol. The supplementation with α‐tocopherol preserved sperm plasma membrane, reflected not only in the acrosome integrity but also in a greater efficiency of energy production.
BioMatrix® Biolimus A9®-eluting coronary stent: a next-generation drug-eluting stent for coronary artery disease

Drug-eluting stent technology consisting of a bare metal stent, carrier coating, bioactive drug and delivery system, offers an almost infinite range of possible device configurations. A growing understanding of the mechanisms of restenosis allows for the design of synergistic functions within these components, thus providing a basis for new and improved products. The BioMatrix® stent (Biosensors Interventional Technologies Pte Ltd., Singapore) elutes the new sirolimus derivative Biolimus A9® from a biodegradable polylactic acid polymer. Biolimus A9 possesses enhanced anti-inflammatory and antiproliferative activity with an improved pharmacokinetic profile. Permanent polymer-carrier-based platforms may be associated with inflammation, late thrombosis and restenosis. The BioMatrix, with its asymmetric and abluminal coating, releases Biolimus A9 into the vessel wall while the polylactic acid polymer is resorbed by surrounding tissues. Clinical studies have demonstrated the BioMatrix to be well tolerated and effective, and it has now become the subject of an aggressive clinical program.
Distribution of Diazepam and Nordiazepam Between Plasma and Whole Blood and the Influence of Hematocrit

The binding of drugs to plasma proteins is important to consider when concentrations in whole blood (eg, in forensic toxicology) are compared with therapeutic and toxic concentrations based on the analysis of plasma or serum. The plasma to whole blood distribution of diazepam (D) and its major metabolite nordiazepam (ND) was investigated under in vitro and ex vivo conditions. Studies in vitro were done by spiking whole blood with D and ND to give concentrations ranging from 0.1 to 1.0 μg/g. Venous blood was also obtained from hospital blood donors (n = 66) after informed consent. The hematocrit, hemoglobin, and water content of blood specimens were determined by routine procedures before D and ND were added to produce target concentrations of ~0.5 μg/g for each substance. The ex vivo work was done with blood specimens from hospital outpatients who were being medicated with D. Concentrations of D and ND were determined in body fluids by capillary column gas chromatography after adding prazepam as internal standard and solvent extraction with butyl acetate. The method limit of quantitation was 0.03 μg/g for both D and ND. The concentrations of D and ND were highest in plasma and lowest in erythrocytes. The plasma/blood (P/B) distribution ratios did not depend on drug concentration between 0.1 and 1.0 μg/g. The mean P/B ratios were 1.79:1 for D and 1.69:1 for ND when hematocrit was 45%. Furthermore, the P/B ratio for D (y) was positively correlated with blood hematocrit (x) and the regression equation was y = 0.636 + 0.025 x (r = 0.86, P < 0.001). A similar strong association was found between the P/B ratio and hematocrit for ND (r = 0.79). P/B ratios of D and ND, blood hematocrit, hemoglobin, and the water content differed between sexes (P < 0.001). The overall mean P/B ratios for D and ND were 1.69 ± 0.097 (± SD) and 1.62 ± 0.08 (P < 0.001, n = 66) respectively when the mean hematocrit was 42.9 ± 3.4 (± SD). For forensic purposes, it would be better to forgo making any conversion of a drug concentration measured in whole blood to that expected in plasma or serum; instead, therapeutic and toxic concentrations should be established for the actual specimens received.