Miracle-dz/UniFAR-FTUs huggingface dataset:
Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by &agr;-Ketoglutarate and TET-TDG Functional Reactivation

Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of &agr;-ketoglutarate (&agr;KG) in the epimetabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing, and gene-specific GC methylation detection revealed an accumulation of 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine in the genomic DNA of human CMSCs isolated from diabetic donors. Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high-fat diet (HFD), injected with streptozotocin, or both in combination (streptozotocin/HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of &agr;KG synthesis in diabetic CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised TDG (thymine DNA glycosylase) and TET1 (ten–eleven translocation protein 1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that &agr;KG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatches or 5-formylcytosine. Accordingly, an exogenous source of &agr;KG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization, and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5-formylcytosine accumulation, thus partially mimicking the diabetic epigenetic landscape in cells of nondiabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of &agr;KG dehydrogenase, increased the &agr;KG level in diabetic CMSCs and in the heart of HFD and streptozotocin mice eliciting, in HFD, DNA demethylation, glucose uptake, and insulin response. Conclusions: Restoring the epimetabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes.
One's fault is another's lesson: What motivates the employees to Participate in the learning activity?

Many companies seem poor at learning from failure even though managers in which know the importance of it to improve their business performance. There is, however, a unique company in Japan, which has succeeded in establishing their learning system from failure and has never repeated same failure (according to the executives in the company). Authors explored the key success factors of their learning-from-failure through interviews and questionnaire to employees. We find that there is mutual benefit between fault-disclosing employee and disclosed employee, and it can be one of the keys to succeed in learning from failure.
Heterogeneous Firms, Urban Costs and Agglomeration

This paper explores how the interaction between firm heterogeneity, urban costs and transport costs determines spatial configuration across regions within a simple general equilibrium model. We shed light on how firm heterogeneity affects the centrifugal and centripetal forces and reshapes the spatial configuration of an urban space economy. We show analytically that an increase in firm heterogeneity increases the range in which a symmetric equilibrium is stable. In addition, full agglomeration is shown to be always sustainable, which complements existing results in literature.
CORE: An accurate congestion detection method in IEEE 802.11 wireless mesh networks

Although IEEE 802.11 wireless mesh networks (WMNs) provide low-cost extension of wireless Internet access coverage, the wide adoption of WMNs is limited due to the bandwidth scarcity. One of the important mechanisms to fully utilize the scarce bandwidth is congestion control. Especially, congestion detection, a module of congestion control, plays an essential role since the source rates should be adapted according to the detected network congestion. Due to the various dynamics of IEEE 802.11 WMNs, wireless congestion control mechanisms usually use complicated combination of various metrics, such as channel-idle time, interface queue length and average link-layer retransmission in intermediate nodes. However, this metric combination requires the sophisticated design of congestion control mechanism and eventually leads to the optimization difficulty. Thus, we propose a simple-yet-effective congestion detection metric, CORE (COngestion Residual timE). CORE measures the expected time of congestion-loss occurrence on the interface queue between IP and MAC layers. We obtain CORE by measuring the residual queue length and the slope of the queue length and then refining them with signal processing schemes (e.g., triangular moving average and linear regression). Moreover CORE provides over-generated rate information that is essential to the congestion control mechanisms. By taking a series of experiments, we verify that CORE accurately predicts the time of congestion-loss occurrence as well as the over-generated rate.
PROBABLE MALINGERING AND PERFORMANCE ON THE TEST OF VARIABLES OF ATTENTION

Fifty subjects with mild head injury involved in personal injury litigation and 2 subjects referred for evaluation of their disability status underwent comprehensive neuropsychological examination including the Test of Variables of Attention (TOVA). Group status was determined by performance on symptom validity testing. Twenty-six subjects who failed symptom validity testing formed the probable malingering (PM) group, while 26 subjects who passed symptom validity testing comprised the not malingering (NM) group. Subjects in the PM group performed significantly worse on all TOVA variables relative to subjects in the NM group. Discriminant function analyses revealed that TOVA omission errors ≥3 errors was the best predictor of group status. Malingering research employing a group of probable clinical malingerers has direct generalizability to real-world settings.
Late Stroke: Comparison of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Multivessel Disease and Unprotected Left Main Disease A Meta-Analysis and Review of Literature

Background and Purpose— Studies have suggested that the early excess risk of stroke in coronary artery bypass grafting (CABG) may be compensated for by a slow but progressive catch-up phenomenon in patients undergoing percutaneous coronary intervention (PCI). We therefore undertook this analysis to compare the temporal stroke risk between PCI and CABG in patients with unprotected left main stenosis and multivessel coronary artery disease. Methods— Studies of PCI versus CABG for unprotected left main stenosis and multivessel disease published between January 1994 (stent era) and July 2013 were identified using an electronic search and reviewed using meta-analytic techniques. Results— We selected 57 reports for the meta-analysis by applying the inclusion and exclusion criteria. The analysis was performed on 80 314 patient records. There was a significantly lower risk of cumulative stroke in patients undergoing PCI with stenting at 1 year (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.42–0.71), 2 years (OR, 0.78; 95% CI, 0.66–0.92), 3 years (OR, 0.79; 95% CI, 0.67–0.92), 4 years (OR, 0.74; 95% CI, 0.56–0.97), and 5 years (OR, 0.79; 95% CI, 0.69–0.91). There was no significant difference in the incidence of stroke because of the small sample size (OR, 0.71; 95% CI, 0.46–1.08) at >5 years between PCI and CABG. Similar results were observed on subgroup analysis (multi-vessel coronary artery disease, unprotected left main, diabetics, and randomized trials) and for stroke within 30 days. Late stroke (stroke >30 days) was similar between the 2 groups. Conclusions— There is a significantly lower risk of stroke within 30 days and cumulative stroke with PCI as compared with CABG up to year 5. There is no late catch up of stroke in the PCI arm. The risk of stroke should be weighed in deciding between revascularization strategies.
Auctioned IPOs: The U.S. Evidence

Between 1999 and 2007, WR Hambrecht has completed 19 IPOs in the U.S. using an auction mechanism. We analyze investor behavior and mechanism performance in these auctioned IPOs using detailed bidding data. The existence of some bids posted at high prices suggests that some investors (mostly retail) try to free-ride on the mechanism. But institutional demand in these auctions is very elastic, suggesting that institutional investors reveal information in the bidding process. Investor participation is largely predictable based on deal size, and demand is dominated by institutions. Flipping is equally prevalent in auctions as in bookbuilt deals – but unlike in bookbuilding, investors in auctions tend to flip their shares more in cold deals. Finally, we find that institutional investors, who provide more information, are rewarded by obtaining a larger share of the deals that have higher initial returns. Our results therefore suggest that auctioned IPOs could be an effective alternative to traditional bookbuilding.
The effects of spatial movement components precues on the execution of rapid aiming in children aged 7, 9, and 11.

The aim of the present study was twofold: first, to investigate the effects of spatial precues on the execution of rapid aiming in children aged 7, 9, and 11 and second, to provide a kinematic support to the investigation of the role of precues in aiming tasks performed under temporal constraints. Four precuing conditions were used, where participants received: (a) no precue of any type, (b) advance information on direction, (c) advance information on amplitude, and (d) complete information on the forthcoming movement. Our results showed that precuing the spatial dimensions of movement shortens reaction times, that such shortening is a function of the number of precued parameters, and that spatial precues modify the kinematics of the children's rapid aiming movements. Peak velocity increased with direction and/or amplitude, suggesting that precues play a significant role in motor preparation. Moreover, the accuracy results indicate that direction precuing induces a proactive directional regulation. Finally, direction and amplitude appear to be independently specified in children.
A dynamic model for the redesign of a product and its upstream supply chain integrating PLM (Product Lifecycle Management) approach

This paper deals with a recent approach that tackles the product and the supply chain design issues at the same time. The simultaneous design of a product and its supply chain is relevant. In fact, supply chain decisions incorporated during the early phases of the product design enhance its performance. Therefore, collaboration among all supply chain partners is very important, especially at the product design phase. In this paper, we investigate the role of the PLM (Product Life Cycle Management) as a key to integrating product and supply chain optimization. We study the case of an existing product's redesign. The design change affects either the components or the process of the product or both of them at once. First, we present an UML model for designing the product and its supply chain integrating PLM. Then, we propose a mixed integer linear programming (MILP) formulation to determine simultaneously the optimal redesign alternative accompanied with its optimal upstream supply chain configuration. Being at a strategic design, time periods in the mathematical model are considered to be product life cycle phases. This consideration gave a dynamic aspect to the model. Finally a numerical example is given to illustrate the application of the model.
Cognitive dysfunction mediates the effects of poor physical fitness on decreased functional independence in heart failure

Heart failure (HF) patients require assistance with activities of daily living (ADL). Poor physical fitness has recently been identified as a contributor to the high rates of disability in HF, though the mechanisms for such effects are unclear. Although not previously examined, decreased fitness might adversely impact ADL in HF through its known association with cognitive impairment, a key correlate of self‐care abilities in this population. We sought to test this possibility using a model‐based approach.
Neonatal mechanical ventilation: Indications and outcome

Background and Aims: Decreasing mortality in sick and ventilated neonates is an endeavor of all neonatologists. To reduce the high mortality in this group of neonates, identification of risk factors is important. This study was undertaken to find out the indications of ventilation and complications in ventilated neonates and also study possible predictors of outcome. Subjects: Age <1-month; mechanically ventilated; not having suspected metabolic disorders or congenital anomalies; excluding postoperative patients. Methods: Neonates consecutively put on mechanical ventilation during the study period (October 2011 to November 2013) enrolled. Primary disease of the neonates along with complications present listed. Clinical and laboratory parameters analyzed to find the predictors of mortality. Results: Total 300 neonates were ventilated. 52% were male. Mean age, weight, and gestational age were 21 ± 62 h, 2320 ± 846.2 g, and 35.2 ± 4.9 weeks, respectively. 130 (43%) neonates died. Respiratory distress syndrome (RDS) (31.1%), sepsis (22.7%), and birth asphyxia (18%) were the most common indications for ventilation. Mortality in ventilated patients with sepsis, pneumonia, RDS or birth asphyxia was 64.7%, 60%, 44.6%, and 33.3%, respectively. Weight <2500 g, gestation <34 weeks, initial pH <7.1, presence of sepsis, apnea, shock, pulmonary hemorrhage, hypoglycemia, neutropenia, and thrombocytopenia were significantly associated with mortality (P < 0.05). Resuscitation at birth, seizures, intra ventricular hemorrhage, pneumothorax, ventilator-associated pneumonia, PO2, or PCO2 did not have a significant association with mortality. On logistic regression, gestation <34 weeks, initial pH <7.1, pulmonary hemorrhage, or shock were independently significant predictors of mortality. Conclusions: Weight <2500 g, gestation <34 weeks, initial arterial pH <7.1, shock, pulmonary hemorrhage, apnea, hypoglycemia, neutropenia, and thrombocytopenia were significant predictors of mortality in ventilated neonates.
Control of mixed pattern AID S-tuberculosis co-infection a sub-optimal approach of the resource allocation

This work concerns a problem of decision in the field of epidemiological control. The main objective is the optimal allocation of a limited amount of resources in such a way that the direct and social costs are minimized in terms of co-infection: acquired immune deficiency syndrome (AIDS) and tuberculosis. A mathematical model for the dynamics of the co-infection found in the literature is used together with a cost functional of quadratic type to yield an optimal control problem. The class of admissible controls was then restricted to be piecewise constant functions, characterized by the heights and the breakpoints, to reflect the form that the financial resources from health authorities are made available. The sub-optimal control problem is to choose a piecewise constant function that minimizes the cost functional, now written in as a mathematical programming problem which is solved using a numerical method that searches for global solutions. In this work the method of flexible polyhedra with simulated annealing and multiple random initializations is used. Numerical simulations in a digital computer show that the increase in the fraction of the population affected by AIDS tends to be significantly slowed, although not reduced as no cure is yet known.
Cyclophosphamide causes osteoporosis in C57BL/6 male mice: suppressive effects of cyclophosphamide on osteoblastogenesis and osteoclastogenesis

The clinical evidence indicated that cyclophosphamide (CPD), one of the chemotherapy drugs, caused severe deteriorations in bones of cancer patients. However, the exact mechanisms by which CPD exerts effects on bone remodeling is not yet fully elucidated. Therefore, this study was performed to investigate the role and potential mechanism of CPD in osteoblastogenesis and osteoclastogenesis. Here it was found that CPD treatment (100mg/kg/day) for 7 days led to osteoporosis phenotype in male mice. CPD inhibited osteoblastogenesis as shown by decreasing the number and differentiation of bone mesenchymal stem cells (MSCs) and reducing the formation and activity of osteoblasts. Moreover, CPD suppressed the osteoclastogenesis mediated by receptor activator for nuclear factor-κ B ligand (RANKL) as shown by reducing the maturation and activity of osteoclasts. At the molecular level, CPD exerted inhibitory effect on the expression of components (Cyclin D1, β-catenin, Wnt 1, Wnt10b) of Wnt/β-catenin signaling pathway in MSCs and osteoblasts-specific factors (alkaline phosphatase, Runx2, and osteocalcin). CPD also down-regulated the expression of the components (tumor necrosis factor receptor-associated factor 6, nuclear factor of activated T-cells cytoplasm 1, c-Fos and NF-κB) of RANKL signaling pathway and the factors (matrix metalloproteinase 9, cathepsin K, tartrate-resistant acid phosphates and carbonic anhydrase II) for osteoclastic activity. Taken together, this study demonstrated that the short-term treatment of CPD induced osteoporosis in mice and the underlying mechanism might be attributed to its marked suppression on osteoblastogenesis and osteoclastogenesis, especially the effect of CPD on bone formation might play a dominant role in its detrimental effects on bone remodeling.
Y-sukupolvi luonnossa:

Urbanization and modernization have led to changes in the ways people use nature. While the public use ofnature is changing from subsistence to recreation, the amount of direct contact with nature has appearedto decrease in Western societies. Younger generations’ alienation from nature has been recently discussedin Finland, too. This article explores young people’s outdoor recreation and relationship with nature. Theresearch questions are: 1) how do young people born in the 1990s, the so called Generation Y, recreateoutdoors, 2) what values and meanings do they attach to natural areas and outdoor recreation, and 3) howdoes their relationship with nature develop? This study is based on thematic writings and surveys completedby 15–21 year old people living in the Lahti region (N=184). Results indicate the polarization in relationto nature: for some young people nature is an integral part of their lives while some are not interested innature. The number of people not connected to nature may increase as urbanization continues. Nevertheless,it is challenging to forecast the future as outdoor recreation seems to be connected to people’s ageand life phase. Outdoor recreation may thus increase among these young people in later phases of life.
Gas Cascade Amplification in Ultra-High-Resolution Environmental Scanning Electron Microcopy

Abstract We describe a feedback mechanism in the gas cascade amplification process used in magnetic immersion lens environmental scanning electron microcopy (ESEM). Feedback dominates gas gain under the conditions typically used for ultra-high-resolution ESEM and gives rise to novel dependencies of the imaging signal and noise on microscope operating parameters. It is ascribed tentatively to the generation of free electrons upon de-excitation of metastable species in the gas cascade. The results have implications for optimization of ESEM systems for applications such as critical dimension metrology and real-time imaging of nanostructure growth by gas mediated electron beam induced deposition.
Improved current control strategy for power conditioners using sinusoidal signal integrators in synchronous reference frame

In this paper, an improved current control scheme for shunt type power conditioners is proposed, with the aim of simplifying current harmonic compensation for industrial implementations where strict limitations on the harmonic distortion of the mains currents are required. To compensate current harmonics, the proposed scheme is based on proportional-integral regulators using sinusoidal signal integrators, implemented to operate both on positive and negative sequence signals. One regulator, for the fundamental current component, is implemented in the stationary reference frame. The other regulators, for the current harmonics, are implemented in a synchronous reference frame rotating at the fundamental frequency. This allows to compensate simultaneously two current harmonics with just one regulator. The whole control algorithm has been implemented on a 16-bit, Fixed-point digital signal processor (DSP) platform controlling a 20 kVA prototype. Experimental results are presented to show the validity of the proposed solutions.
Sequence variations of NKX2-5 and HAND1 genes in patients with atrial isomerism.

OBJECTIVE Atrial isomerism is a congenital disorder, which is characterized by lateralization defects in normally asymmetrical developing organs like the heart. Atrial isomerism is supposed to be caused by molecular defects during early development. The NKX2-5 is a cardiac specific transcription factor, which initiates and regulates downstream transcriptional cascades of cardiogenesis. The HAND1 is another transcription factor expressed in the heart, and it is characterized by an asymmetrical pattern of expression. In this study, we aimed to test whether mutations in NKX2-5 and HAND1 genes play a role in the etiology of atrial isomerism. METHODS This case-control study consisted of 70 patients who underwent surgical treatment for congenital heart defects including atrial isomerism, 80 healthy subjects (HAND1 gene) and 40 healthy subjects (NKX2-5 gene). All exons and exon-intron boundaries of NKX2-5 and HAND1 genes were analyzed by SSCP, and suspected samples were sequenced for mutation analysis. Digestion with appropriate restriction enzymes was performed for analysis of known mutations and polymorphisms. The frequencies of the alleles and the genotypes were compared among patient and control groups using the Chi-square and the Fisher tests when appropriate. RESULTS In intronic region of HAND1 gene, we identified a C>G substitution both in patients and controls. Frequency of mutant allele (11, 42%) was found higher (p=0.046) in patient group than that of the control group (2.5%). Association between atrial isomerism and genotypes with mutant allele was found borderline significant (p=0.054). In NKX2-5 gene, we identified heterozygous Q170X (Gln170ter) mutation in one patient. We did not found any correlation between defined sequence variations and clinical properties of the patients. CONCLUSION Our results suggest that mutations or sequence variations in HAND1 or NKX2-5 genes may play role in etiology or pathogenesis of atrial isomerism.
The Structure of the Yeast Plasma Membrane SNARE Complex Reveals Destabilizing Water-filled Cavities*

SNARE proteins form a complex that leads to membrane fusion between vesicles, organelles, and plasma membrane in all eukaryotic cells. We report the 1.7Å resolution structure of the SNARE complex that mediates exocytosis at the plasma membrane in the yeast Saccharomyces cerevisiae. Similar to its neuronal and endosomal homologues, the S. cerevisiae SNARE complex forms a parallel four-helix bundle in the center of which is an ionic layer. The S. cerevisiae SNARE complex exhibits increased helix bending near the ionic layer, contains water-filled cavities in the complex core, and exhibits reduced thermal stability relative to mammalian SNARE complexes. Mutagenesis experiments suggest that the water-filled cavities contribute to the lower stability of the S. cerevisiae complex.