Miracle-dz/UniFAR-FTUs huggingface dataset:
Importance of mitral regurgitation in ischaemic heart disease--more than just a bystander.

This editorial refers to ‘Prognostic influence of mitral regurgitation prior to a first myocardial infarction’† by J. Zamorano et al. , on page 343 Coronary artery disease (CAD) prognosis has been known for many years to depend on many factors, including the degree of left ventricular (LV) dysfunction as well as the presence of inducible ischaemia, viable dysfunctioning myocardium, and degree of coronary artery lesions. Mitral regurgitation (MR) is often a bystander and is a frequent finding after acute myocardial infarction (AMI) (in 15–64% of patients). It is an independent predictor of cardiovascular mortality,1–4 and results from many factors, such as papillary muscle dysfunction and/or mitral annulus dilatation, and LV remodelling with papillary muscle migration causing malcoaptation of the leaflets and excess valvular tenting with loss of systolic annular contraction.2 Myocardial viability in the infarct area reduces infarct expansion and ventricular remodelling, and prevents the development of MR. In the study by Golia et al. 1 of 191 patients after uncomplicated AMI, MR was present in 58.6% of the patients and it was significant (>grade 1) in 26 patients (13.6%). It was associated with increased age, lower regional wall motion score index during dobutamine stress echocardiography, more severe CAD, and more frequent anterior/inferior infarctions. At multivariate analysis the extent of LV dysfunction and the presence of MR were significantly related to mortality. Auscultation may not detect a murmur due to decreased turbulence, and echocardiography should be performed routinely on all patients for diagnosis. A regurgitant volume ≥30 mL, or an effective regurgitant orifice ≥2 mm2 defines a high-risk group.4,5 Many papers have focused on the importance of correcting MR during coronary artery bypass grafting (CABG) for a better long-term prognosis, even when there is no definite major organic cause (such … *Tel: +351 21 8465469; fax: +351 21 8465469. E-mail address: branco.online{at}mail.telepac. pt
The Med1 Subunit of the Mediator Complex Induces Liver Cell Proliferation and Is Phosphorylated by AMP Kinase*

Background: The Med1 subunit of the Mediator complex orchestrates metabolic pathways of energy metabolism. Results: Overexpression of Med1 in liver enhances hepatocyte proliferation and the cellular energy sensor AMPK phosphorylates Med1. Conclusion: Med1 is essential for hepatocellular proliferation and energy homeostasis downstream to AMPK. Significance: Med1 and its phosphorylation by AMPK may have important implications in the pathophysiology of liver. Mediator, a large multisubunit protein complex, plays a pivotal role in gene transcription by linking gene-specific transcription factors with the preinitiation complex and RNA polymerase II. In the liver, the key subunit of the Mediator complex, Med1, interacts with several nuclear receptors and transcription factors to direct gene-specific transcription. Conditional knock-out of Med1 in the liver showed that hepatocytes lacking Med1 did not regenerate following either partial hepatectomy or treatment with certain nuclear receptor activators and failed to give rise to tumors when challenged with carcinogens. We now report that the adenovirally driven overexpression of Med1 in mouse liver stimulates hepatocyte DNA synthesis with enhanced expression of DNA replication, cell cycle control, and liver-specific genes, indicating that Med1 alone is necessary and sufficient for liver cell proliferation. Importantly, we demonstrate that AMP-activated protein kinase (AMPK), an important cellular energy sensor, interacts with, and directly phosphorylates, Med1 in vitro at serine 656, serine 756, and serine 796. AMPK also phosphorylates Med1 in vivo in mouse liver and in cultured primary hepatocytes and HEK293 and HeLa cells. In addition, we demonstrate that PPARα activators increase AMPK-mediated Med1 phosphorylation in vivo. Inhibition of AMPK by compound C decreased hepatocyte proliferation induced by Med1 and also by the PPARα activators fenofibrate and Wy-14,643. Co-treatment with compound C attenuated PPARα activator-inducible fatty acid β-oxidation in liver. Our results suggest that Med1 phosphorylation by its association with AMPK regulates liver cell proliferation and fatty acid oxidation, most likely as a downstream effector of PPARα and AMPK.
A method of progressive constraints for manipulation planning

We present a method for manipulation planning derived from a systematic approach to constrained motion planning. We call it a method of progressive constraints. It replaces an original problem by a series of progressively constrained ones, and makes a solution of the current problem converge toward a solution of the original problem. The manipulation constraints are analyzed and it is shown how they can be introduced progressively. The progressive constraints framework can thus be used for solving manipulation planning problems. The general algorithm proposed for constrained motion planning can be derived from a standard geometric path planner. We use the variational dynamic programming path planner, in which at every iteration a current path is used to generate a submanifold that is searched for a better path.
Bioactive Glass S53P4 in Mastoid Obliteration Surgery for Chronic Otitis Media and Cerebrospinal Fluid Leakage

Objectives: We evaluated the results of cases of chronic otitis media treated with mastoid obliteration surgery using bioactive glass S53P4. Methods: Twenty-five patients with chronic otitis media and 1 patient with cerebrospinal fluid leakage without chronic infection were treated with bioactive glass S53P4. Twenty patients had had previous surgery because of chronic otitis media with or without cholesteatoma. A mastoid obliteration was performed with bioactive glass S53P4 granules and a musculoperiosteal flap with or without bone paté. In 2 patients with a bony dehiscence at the middle cranial fossa, a bioactive glass plate was used to support the protruding dura. In addition, in 3 patients, occlusion of a dural fistula was needed. The median follow-up period was 34.5 months (range, 1 to 182 months). Results: Excluding the 2 patients with only 1 month of follow-up at our department, 96% of the patients had a dry, safe ear or only intermittent otorrhea. In 92% of the patients, the objective of achieving a smaller or nonexistent cavity was achieved. Conclusions: Bioactive glass S53P4 is a noteworthy material in mastoid obliteration surgery.
Beehive-an Internet integrated collaborative learning environment

We aim at describing the building of educational software for collaborative learning based on Constructivism, using multimedia resources, having adults as its target public. The final product was a CD-ROM prototype of a learning environment to be used in connection with the Internet in order to socialize the students' synthesis based on questioning in the CD-ROM, to visualize the peers' contributions, to debate and clarify doubts and to pose new questions. First, we introduce the metaphor used in the application, the beehive. Next, we describe the connection of the collaborative learning approach to the use of an integrated system made by a CD-ROM and the Web for educational purposes. We then show the development of the environment based on the metaphor. Following this, we describe the prototype pages. Finally, we briefly mention the possible applications of the beehive metaphor and the integration of a multimedia CD-ROM with the Internet.
Spinal oscillators in man under normal and pathologic conditions.

1. Single-fibre action potentials (APs) were recorded from lower sacral nerve roots of brain-dead humans (HTs) and two paraplegics with thoracical spinal cord lesions. Impulse patterns of single oscillatory firing alpha 2 and alpha 3-motoneurons were identified and analysed. An alpha 2-motoneuron fired typically with 3 AP impulse trains every 160 msec. 2. In stable spinal oscillators of HTs the oscillation period was 70 msec plus 30 msec times the number of APs per impulse train; the respective values in paraplegics were 35 msec plus 40 msec times the number of APs per impulse train. These linear relationships indicate that spinal oscillators consist of at least 2 kinds of nerve cells. 3. Successive interspike intervals (IIs) of the impulse trains increased from about 3.5 msec to over 10 msec in paraplegics similarly as was the case in HTs. 4. The distributions of the first IIs (of impulse trains) and of the oscillation period of unstable continuously oscillatory firing alpha 2-motoneuron showed similar peaks. By relating the peak values of the first II and the oscillation period, a shortest II of 3.5 msec was obtained in a HT and a paraplegic, and a shortest oscillation period of 70 msec was measured in a HT and 40 msec in a paraplegic. The derivation of the shortest II of 3.5 msec from the oscillation itself is taken as an indication for alpha 2-motoneurons being included in the spinal oscillator function, since the shortest soma-dendritic spike intervals of motoneurons is expected to be 3.5 msec. 5. The spinal oscillator of a paraplegic showed more and higher activity changes than that in a HT as if spinal oscillators in paraplegics were insufficiently damped. 6. By interpreting the peaks in oscillation period distributions of unstable oscillators as being different oscillation loop pathways, it is speculated that the oscillators consist of the motoneuron, to which different interneuron pathways are connected. A contrasting of pathways with increasing excitation of the oscillator was observed. 7. The comparison of possible loop pathways of oscillation between paraplegics and HTs (closer to normal) indicates that the loss of descending tracts in paraplegics and the adaptation to it result in an increase of the oscillation pathways for alpha 2-oscillators from 1 to 3 in HTs to up to 6 in paraplegics. 8. Different measured and theoretically predictable spinal alpha 2-oscillators can cover altogether a frequency range between 5 and 10 Hz. (ABSTRACT TRUNCATED AT 400 WORDS)
High voltage photovoltaic system implementing Si/SiC-based active neutral-point-clamped converter

This article proposes a power converter solution for 1.5 kV DC photovoltaic applications and benchmark the benefits of commercially available SiC MOSFETS for the system power efficiency. The circuit solution is based on a full power factor three-level active neutral-point-clamped converter featuring reduced numbers of high-frequency switched semiconductors. A combination of Si IGBT and SiC MOSFET is selected for the converter implementation because of the tradeoff between system cost and power efficiency. Finally, the advantages of the proposed converter is verified by the analysis of a 200 kVA power generation system employing this solution and other conventional two- and three-level voltage source converters.
C6 ceramide dramatically increases vincristine sensitivity both in vivo and in vitro , involving AMP-activated protein kinase–p53 signaling

Use of the conventional cancer chemotherapy (i.e. vincristine) is limited in tumor cells exhibiting pre-existing or acquired resistance. Here, we found that C6 ceramide (C6) dramatically sensitized vincristine’s activity. In vitro , C6 and vincristine coadministration induced substantial necrosis and apoptosis in multiple human cancer cell lines, which were accompanied by a profound AMP-activated protein kinase (AMPK) activation, subsequent p53 activation, mTORC1 inactivation and Bcl-2/HIF-1 α downregulation. Such synergistic effects were attenuated by AMPK inactivation through genetic mutation or short hairpin RNA silencing. Coadministration-activated p53 translocated to mitochondria, and formed a complex with cyclophilin-D, leading to mitochondrial permeability transition pore opening and cell necrosis. Disrupting p53–Cyp-D complexation through pharmacological or genetic means reduced costimulation-induced cytotoxicity. In vivo , a liposomal C6 was synthesized, which dramatically enhanced the antiproliferative activity of vincristine on HCT-116 or A2780 xenografts. Together, C6 sensitizes vincristine-induced anticancer activity in vivo and in vitro , involving activating AMPK–p53 signaling.
Influence of Acute Bouts of Exercise on Blood Glucose in Type 2 Diabetic Patients, as Measured by Continuous Glucose Monitoring Systems

Literature data indicate that the effect on blood glucose levels of a single bout of exercise may persist up to 48-h after cessation of exercise. Regular exercise improves insulin sensitivity and blood glucose control in subjects with type 2 diabetes and is considered a key element in the management of this condition. However, adaptive responses to exercise are altered in diabetic subjects and medications used in these patients may cause inappropriate insulin levels for the concurrent blood glucose concentrations, with a possible increase in risk for hypoglycaemia. Recently, the development and clinical availability of systems for the continuous monitoring of glucose (continuous glucose monitoring system, CGMS), have made it possible to continuously record blood glucose levels for several days in real life conditions, showing that possible differences in blood glucose levels of these individuals may occur during and after a single bout of exercise, depending on the characteristics of the physical activity. In particular, differences between aerobic vs resistance exercise and between low-intensity vs high-intensity exercise have been reported. However, there are only a few, small heterogeneous studies on this topic, and results are to some extent discordant, limiting any conclusions. Further research on this issue is needed before we can reach clear conclusions. In particular, the role of differences in frequency, duration, intensity, type and timing of exercise needs to be carefully investigated. Hopefully, this information will assist clinicians and exercise specialists in designing personalized exercise programmes and strategies aimed at optimally improving glucose control of type 2 diabetic patients, also limiting the risk for hypoglycaemia. In this article, we review the literature regarding the acute effect of different types of exercise on glucose levels, as measured by CGMS, in subjects with type 2 diabetes.
Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity

Production of a potent urease has been described as a trait common to all Helicobacter pylori so far isolated from humans with gastritis as well as peptic ulceration. The detection of urease activity from genes cloned from H. pylori was made possible by use of a shuttle cosmid vector, allowing replication and movement of cloned DNA sequences in either Escherichia coli or Campylobacter jejuni. With this approach, we cloned a 44-kb portion of H. pylori chromosomal DNA which did not lead to urease activity when introduced into E. coli but permitted, although temporarily, biosynthesis of the urease when transferred by conjugation to C. jejuni. The recombinant cosmid (pILL585) expressing the urease phenotype was mapped and used to subclone an 8.1-kb fragment (pILL590) able to confer the same property to C. jejuni recipient strains. By a series of deletions and subclonings, the urease genes were localized to a 4.2-kb region of DNA and were sequenced by the dideoxy method. Four open reading frames were found, encoding polypeptides with predicted molecular weights of 26,500 (ureA), 61,600 (ureB), 49,200 (ureC), and 15,000 (ureD). The predicted UreA and UreB polypeptides correspond to the two structural subunits of the urease enzyme; they exhibit a high degree of homology with the three structural subunits of Proteus mirabilis (56% exact matches) as well as with the unique structural subunit of jack bean urease (55.5% exact matches). Although the UreD-predicted polypeptide has domains relevant to transmembrane proteins, no precise role could be attributed to this polypeptide or to the UreC polypeptide, which both mapped to a DNA sequence shown to be required to confer urease activity to a C. jejuni recipient strain.
Estimating the Performance of DD OFDM Optical Systems Impaired by In-Band Crosstalk Using the Moment Generating Function

A theoretical method to assess the impact of in-band crosstalk on the performance of orthogonal frequency division multiplexing (OFDM) communication systems with direct-detection (DD) is presented. The proposed method relies on the moment generating function (MGF) to estimate the bit error rate (BER) of the DD OFDM communication system and takes into account in-band crosstalk, detected noise, and arbitrary electrical filtering at the receiver. By comparison with Monte Carlo simulation, we show that the MGF-based method predicts accurately the BER for different crosstalk levels, subcarriers numbers, 4-ary, 16-ary, and 64-ary quadrature amplitude modulation mappings, carrier-to-signal power ratios, ideal and nonideal electrical filtering, and different types of linearly mapped OFDM signals used in DD. The accuracy of the proposed method may be severely diminished in presence of significant signal distortion due to the nonlinearity of the optical modulator as, in this case, the assumptions of the proposed method do not hold. We also show that the DD OFDM optical systems tolerance to in-band crosstalk is lower than in single-carrier coherent detection optical systems, and it is significantly lessened when the modulation order in the OFDM subcarriers increases.
Streamlined discovery of cross-linked chromatin complexes and associated histone modifications by mass spectrometry

Significance Scientists have developed many affinity pulldown methods to characterize protein networks. Three persistent challenges with current approaches are capturing labile interactions, isolating insoluble DNA-bound complexes, and preserving modifications potentially important for binding specificity. This report presents a cross-linked affinity approach to meet these challenges and effectively capture interactions that otherwise may be intractable with native affinity techniques. We isolate several Drosophila and human protein complexes to demonstrate the technique’s scalability across a range of initial cell amounts and sources, and we develop the ability to identify the breadth of associated histone and nonhistone modifications in parallel. Our results indicate that cross-linked affinity pulldowns should be broadly useful for comprehensive analyses of chromatin networks. Posttranslational modifications (PTMs) are key contributors to chromatin function. The ability to comprehensively link specific histone PTMs with specific chromatin factors would be an important advance in understanding the functions and genomic targeting mechanisms of those factors. We recently introduced a cross-linked affinity technique, BioTAP-XL, to identify chromatin-bound protein interactions that can be difficult to capture with native affinity techniques. However, BioTAP-XL was not strictly compatible with similarly comprehensive analyses of associated histone PTMs. Here we advance BioTAP-XL by demonstrating the ability to quantify histone PTMs linked to specific chromatin factors in parallel with the ability to identify nonhistone binding partners. Furthermore we demonstrate that the initially published quantity of starting material can be scaled down orders of magnitude without loss in proteomic sensitivity. We also integrate hydrophilic interaction chromatography to mitigate detergent carryover and improve liquid chromatography-mass spectrometric performance. In summary, we greatly extend the practicality of BioTAP-XL to enable comprehensive identification of protein complexes and their local chromatin environment.
Decision tree state tying based on segmental clustering for acoustic modeling

A fast segmental clustering approach to decision tree tying based acoustic modeling is proposed for large vocabulary speech recognition. It is based on a two level clustering scheme for robust decision tree state clustering. This approach extends the conventional segmental K-means approach to phonetic decision tree state tying based acoustic modeling. It achieves high recognition performances while reducing the model training time from days to hours comparing to the approaches based on Baum-Welch training. Experimental results on standard Resource Management and Wall Street Journal tasks are presented which demonstrate the robustness and efficacy of this approach.
Enhanced immunoglobulin levels correlate with infectious complications after surgery in esophageal cancer

Severe septic complications account for the high mortality of patients with esophageal cancer. We examined the levels of immunoglobulins and complements together with infection‐related complications in a large number of patients. Enhancements of IgG, IgA, C3, C4, and CH50 were evident in patients with esophageal cancer and were more predominant compared to findings in cases of gastric cancer. Average levels of IgG and IgA immediately before surgery were significantly higher in esophageal cancer patients with postoperative septic complications than in those without such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of immunoglobulins and complements. It would thus appear that the enhancement of IgG and IgA is associated with the occurrence of infectious complications following surgery for patients with esophageal cancer.
Mapping of CO2 at high spatiotemporal resolution using satellite observations: Global distributions from OCO‐2

[1] Satellite observations of CO2 offer new opportunities to improve our understanding of the global carbon cycle. Using such observations to infer global maps of atmospheric CO2 and their associated uncertainties can provide key information about the distribution and dynamic behavior of CO2, through comparison to atmospheric CO2 distributions predicted from biospheric, oceanic, or fossil fuel flux emissions estimates coupled with atmospheric transport models. Ideally, these maps should be at temporal resolutions that are short enough to represent and capture the synoptic dynamics of atmospheric CO2. This study presents a geostatistical method that accomplishes this goal. The method can extract information about the spatial covariance structure of the CO2 field from the available CO2 retrievals, yields full coverage (Level 3) maps at high spatial resolutions, and provides estimates of the uncertainties associated with these maps. The method does not require information about CO2 fluxes or atmospheric transport, such that the Level 3 maps are informed entirely by available retrievals. The approach is assessed by investigating its performance using synthetic OCO-2 data generated from the PCTM/ GEOS-4/CASA-GFED model, for time periods ranging from 1 to 16 days and a target spatial resolution of 1 � latitude � 1.25 � longitude. Results show that global CO2 fields from OCO-2 observations can be predicted well at surprisingly high temporal resolutions. Even one-day Level 3 maps reproduce the large-scale features of the atmospheric CO2 distribution, and yield realistic uncertainty bounds. Temporal resolutions of two to four days result in the best performance for a wide range of investigated scenarios, providing maps at an order of magnitude higher temporal resolution relative to the monthly or seasonal Level 3 maps typically reported in the literature.