Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular basis for the electrocardiographic J wave.

BACKGROUND The J wave is a deflection that appears in the ECG as a late delta wave following the QRS or as a small secondary R wave (R'). Also referred to as an Osborn wave, the J wave has been observed in the ECG of animals and humans for more than four decades, yet the mechanism underlying its manifestation is poorly understood. The present study investigates the cellular basis for the J wave using an isolated arterially perfused preparation consisting of a wedge of canine right or left ventricle. METHODS AND RESULTS A 12-lead ECG was initially recorded in vivo. After isolation and arterial perfusion of the right or left ventricular wedge, transmembrane action potentials were simultaneously recorded from epicardial, M region, and endocardial transmural sites with three floating microelectrodes. A transmural ECG was recorded concurrently. A J wave was observed at the R-ST junction of the ECG in 17 of 20 adult dogs, usually in leads II, III, aVR, and aVF and the mid to lateral precordial leads. The J wave in the transmural ECG recorded across the wedge was closely associated with the presence of a prominent action potential notch in epicardium but not endocardium. The shape and amplitude of the J wave were found to depend on (1) the transmural distribution of the action potential notch amplitude, (2) the relative time course of the early phases of the action potential (width of notch) at different sites within the wall, (3) sequence of activation, and (4) conduction time across the wall. A highly significant correlation was demonstrated between the amplitude of the epicardial action potential notch and the amplitude of the J wave recorded during interventions that alter the appearance of the electrocardiographic J wave, including hypothermia, premature stimulation, and block of the transient outward current by 4-aminopyridine. Ventricular activation from endocardium to epicardium, with epicardium activated last, was also an important prerequisite for the appearance of the J wave. This sequence permits the establishment of a voltage gradient of the early phases of the action potential after activation (ie, the QRS) is complete. CONCLUSIONS Our results provide the first direct evidence in support of the hypothesis that heterogeneous distribution of a transient outward current-mediated spike-and-dome morphology of the action potential across the ventricular wall underlies the manifestation of the electrocardiographic J wave. The presence of a prominent action potential notch in epicardium but not endocardium is shown to provide a voltage gradient that manifests as a J (Osborn) wave or elevated J-point in the ECG.
Copper Differentially Regulates the Activity and Degradation of Yeast Mac1 Transcription Factor*

Copper is an essential metal ion that is toxic when accumulated to high intracellular concentrations. The yeast Mac1 protein is a copper-sensing transcription factor that is essential for both the activation and inactivation of genes required for high affinity copper ion transport. Here we demonstrate that in response to low copper ion concentrations Mac1 protein is rendered inactive for copper transporter gene transcription. Under high copper ion concentrations Mac1 is degraded in a rapid, copper-specific manner. This degradation is critical to prevent copper toxicity that would otherwise result from sustained expression of the copper transport genes. These results demonstrate that nutritional and toxic copper concentrations elicit distinct fates for the Mac1 copper-sensing transcription factor and establish a new mechanism by which trace metals regulate gene expression.
Transcriptional Restriction of Human Immunodeficiency Virus Type 1 Gene Expression in Undifferentiated Primary Monocytes

ABSTRACT Monocytes are critical precursors of dendritic cells and macrophages, which play an important role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1). HIV-1 postentry infection is blocked in undifferentiated monocytes in vitro, while the underlying mechanisms are not fully understood. HIV-1 Tat-mediated transactivation of the viral long terminal repeat (LTR) promoter is essential for HIV-1 transcription. Two critical cellular cofactors of HIV-1 Tat, cyclin T1 (CycT1) and cyclin-dependent kinase 9 (CDK9), are required for LTR-directed HIV-1 transcription. In addition to the previously identified restrictions in early viral life cycle, we find that HIV-1 gene expression is impaired in undifferentiated primary monocytes. Transfection of monocytes by nucleofection with HIV-1 proviral DNA could not produce infectious HIV-1. The lack of Tat transactivation of the LTR promoter correlated with the impaired HIV-1 gene expression in monocytes. Interestingly, heterokaryons between primary monocytes and a human embryonic kidney cell line restored Tat transactivation of LTR, suggesting that monocytes lack cellular factors required for Tat transactivation. CycT1 protein was undetectable in freshly isolated monocytes and induced in monocyte-differentiated macrophages, while the expression of CDK9 remained constant. Transient expression of CycT1 in undifferentiated monocytes could not rescue Tat transactivation, suggesting that CycT1 is not the only limiting factor of HIV-1 infection in monocytes. Furthermore, monocyte differentiation into macrophages appeared to enhance the phosphorylation of CDK9, which correlated with significantly increased HIV-1 infection in macrophages. Our results provide new insights into HIV-1 infection and regulation in primary monocytes and viral pathogenesis.
Genomic imprinting and cancer.

Although we inherit two copies of all genes, except those that reside on the sex chromosomes, there is a subset of these genes in which only the paternal or maternal copy is functional. This phenomenon of monoallelic, parent-of-origin expression of genes is termed genomic imprinting. Imprinted genes are normally involved in embryonic growth and behavioral development, but occasionally they also function inappropriately as oncogenes and tumor suppressor genes. The evidence that imprinted genes play a role in carcinogenesis will be discussed in this review. Additional information about imprinted genes can be found on the Genomic Imprinting Website at: (http://www.geneimprint.com).
Does increased standardisation in health care mean less responsiveness towards individual patients’ expectations? A register-based study in Swedish primary care

Objective: We explore whether standardisation in health care based on evidence on group level and a public health perspective is in conflict with responsiveness towards individual patient’s expectations in Swedish primary care. Methods: Using regression analysis, we study the association between patient views about providers’ responsiveness and indicators reflecting provider’s adherence to evidence-based guidelines, controlled for characteristics related to providers, including patient mix and degree of competition facing providers. Data were taken from two Swedish regions in years 2012 and 2013. Results: Patients’ views about responsiveness are positively correlated with variables reflecting provider’s adherence to evidence-based guidelines regarding treatment of elderly and risk groups, drug reviews and prescription of antibiotics. A high overall illness, private ownership and a high proportion of all visits being with a doctor are positively associated with patient views about responsiveness. The opposite relation was found for a high social deprivation among enrolled individuals and size of practice. There was no systematic variation with respect to the degree of competition facing providers. Conclusion: Results suggest that responsiveness towards individual patient expectations is compatible with increased standardisation in health care. This is encouraging for health care providers as they are challenged to balance increased demands from both patients and payers.
Right ventricular regional function using MR tagging: Normals versus chronic pulmonary hypertension

Right ventricular (RV) regional function, in both normal and diseased states, is not well characterized. Using 1D MR myocardial tagging, RV and septal intramyocardial segmental shortening was noninvasively measured in ten healthy subjects and in seven patients with chronic pulmonary hypertension. The normal RV free wall regional shortening was not uniform. A pattern of increasing RV free wall short‐axis shortening was found from the RV outflow tract to the RV apex, and a more complex pattern of RV free wall long‐axis shortening was observed. Both regional short‐ and long‐axis shortening were globally reduced in pulmonary hypertension patients, with the greatest decreases in the RV outflow tract and in the basal septal wall region. Regional RV function can be quantitatively evaluated using MR tagging to determine the impact of chronic pulmonary hypertension on RV performance.
As Good as it Gets? The UK Labour Market in Recession and Recovery

Labour markets, both in the UK and internationally, have surprised both in recession and recovery. Contrary to the prior literature summarised in OECD (1994) that argued that unemployment was caused by the levels of unemployment benefits, job protection and other labour market factors including high levels of union density, unemployment grew most in countries a) with large financial sectors (the UK and the USA); b) that had house price bubbles (e.g. Ireland, Latvia, Spain, the UK and the USA); c) that had low levels of job protection and unions (the UK and the USA). By contrast, countries with high levels of job protection and high levels of union bargaining coverage have had relatively small rises in unemployment (e.g. Germany and Austria). 1 The prior literature on the causes of unemployment essentially has nothing to say about this crisis.
Do Dental Composites Always Shrink Toward the Light?

Many of the current light-curing composite restorative techniques are rationalized in compliance with the theory that composite shrinks toward the light. Shrinkage directed toward the margins is believed to be responsible for the observed improved marginal properties. However, the dental literature does not consistently support this theory. Experimental determination of contraction patterns is very difficult. In this study, a finite element technique is used to analyze the direction of composite shrinkage as it cures. The process of polymerization can be characterized by pre- and post-gel phases. The stress developed in a restoration can be relieved quickly by the flow of material still in the pre-gel phase. Residual stresses arise after gelation. Both auto- as well as photo-curing composites were analyzed. In photo-curing composites, the gel-point varies throughout the material with the intensity of the light. Experimentally determined light transmittance data for different materials were used in the simulation. Degree of cure and time-dependent shrinkage properties were also included from experimental measurements. The analysis showed that the shrinkage direction was not significantly affected by the orientation of the incoming curing light, but instead was mostly determined by the bonding of the restoration to the tooth and by the free surfaces. Consequently, differences between the contraction patterns of auto- and photo-cure were minimal. It was concluded that composite does not shrink toward the light, but that the direction is predominantly determined by cavity shape and bond quality. Improved marginal properties should be pursued by the optimization of other factors, such as the polymerization process, the curing procedure, and the bond quality. The direction of shrinkage vectors in response to light position does not seem to be an appropriate criterion for the optimization of marginal quality.
Path planning in polygonal domains for robots with limited turning abilities

Path planning among polygonal obstacles is a well-known problem in robotics. In this paper, we consider the problem of planning a collision-free path for a robot in a polygonal domain from a given source point to a given target point. The robot has two basic limitations: an upper bound on the angle of rotation and a lower bound on the distance between two consecutive turns. We describe an algorithm that runs in O(n4) time and finds a path in accordance with the above limitations. As shown by experiments, the output of the algorithm is much close to the shortest path with the requirements. We further demonstrate how to decompose the algorithm into two phases, preprocessing time and query time. In this way, given a fixed start point and a set of obstacles, we can preprocess a data-structure of size O(n4) in O(n4) time, such that for any query target point we can find the above-mentioned path in O(n2) time.
Transmission Dynamics of Tuberculosis in a High-Incidence Country: Prospective Analysis by PCR DNA Fingerprinting

ABSTRACT We have prospectively analyzed the DNA fingerprints ofMycobacterium tuberculosis strains from a random sample of patients with newly diagnosed tuberculosis in Windhoek, Namibia. Strains from 263 smear-positive patients in whom tuberculosis was diagnosed during 1 year were evaluated, and the results were correlated with selected epidemiological and clinical data. A total of 163 different IS6110 fingerprint patterns were observed among the 263 isolates. Isolates from a high percentage of patients (47%) were found in 29 separate clusters, with a cluster defined as isolates with 100% matching patterns. The largest cluster included isolates from 39 patients. One predominant strain of M. tuberculosiscaused 15% of cases of smear-positive pulmonary tuberculosis in Windhoek. That strain was also prevalent in the north of the country, suggesting that in contrast to other African countries with isolates with high levels of diversity in their DNA fingerprint patterns, only a restricted number of different strains significantly contribute to the tuberculosis problem in Namibia.
Failure of Canine Islet Allotransplantation After Kidney Transplantation

Eight dogs with previously established kidney allografts, immunosuppressed with cyclosporin A, received islet allografts from their respective original kidney donors. The median islet-graft functional survival was only 10.5 days, significantly less than for six similarly immunosuppressed dogs receiving only islet allografts (48.5 days, P < .05). Three of the eight dogs that received sequential kidney and islet allografts had experienced no kidney-graft rejection episodes before islet transplantation, but their islet grafts were all rejected within 19 days. In the pancreatectomized dog, prior donor-specific kidney transplantation has an adverse effect on subsequent islet-graft survival.
Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness.

BACKGROUND Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome. METHODS Ten women diagnosed with PCOS were consecutively included (aged 21-39 years, average 30.2 +/- 1.9 years; body mass index 28.4-42.5 kg/m2, average 37.5 +/- 1.7 kg/m2 (mean +/- s.e.)). Adipocytes were isolated from the subcutaneous fat and, after overnight incubation to recover from insulin resistance due to the surgical cell isolation procedures, they were analyzed for insulin sensitivity. RESULTS The patients with PCOS exhibited marked clinical hyperinsulinemia with 3.6-fold higher blood levels of C-peptide than a healthy lean control group (1.7 +/- 0.2 and 0.5 +/- 0.02 nmol/l respectively, P < 0.0001). The patients with PCOS also exhibited 2.4-fold higher concentrations of serum triacylglycerol (2.1 +/- 0.3 and 0.9 +/- 0.06 mmol/l respectively, P < 0.0001), but only slightly elevated blood pressure (118 +/- 12/76 +/- 6 and 113 +/- 7/72 +/- 6 mmHg respectively, P = 0.055/0.046). However, insulin sensitivity for stimulation of glucose transport in the isolated adipocytes was indistinguishable from a non-PCOS, non-diabetic control group, while the maximal insulin effect on glucose uptake was significantly lower (2.2 +/- 0.2- and 3.8 +/- 0.8-fold respectively, P = 0.02). CONCLUSIONS Subcutaneous adipocytes from patients with PCOS do not display reduced insulin sensitivity. The findings show that the insulin resistance of PCOS is qualitatively different from that of type 2 diabetes.
East and West: Testing the Five Theories in Times of Crisis

Fifteen years after Matthew Gabel's seminal work on support for European integration (1998a), this paper empirically tests again the 'five theories' to explain attitudes towards the EU. In Gabel's article, results show that citizen's support could be explained by both cognitive mobilization and political values (affective dimension), in particular across original member states, while policy effects on welfare, political parties and government support (utilitarian dimension) were determinant in later member states. This paper replicates Matthew Gabel's test on five theories, using the Eurobarometer data. First, it briefly presents the five theories and the most recent findings in the literature; second, it tests the five theories in two case studies: Italy, as one of the founding member states that has undergone economic recession for four years in a row; and Poland, as one of the recent new member states that represented half of the 2004 enlargement and is the eight biggest economy in the EU. Finally, the theories will be tested in comparative perspective. This analysis expects that elites have greater opportunity to influence public opinion in Central and Eastern Europe. However, high levels of distrust for political elites and very low levels of turnout can indicate that the egocentric and sociotropic utilitarian indicators and the affective dimension can be determinant also in post-Communist countries; and recent analyses on the current financial crisis show that national identity and political institutions are increasingly significant in explaining support for the EU. While it is worth noting that party-based euroscepticism does not necessarily translate into public euroscepticism, and there may not be a relationship between eurosceptic or euroenthusiast voting into eurosceptic and euroenthusiast political parties at national and European Parliament elections, this paper stresses the differences and possible convergences across Western and Eastern member states.
Diversification of pre-IPO ownership and foreign IPO performance

We examine the diversification of pre-IPO ownership of foreign-listed firms and how the presence of pre-IPO shareholders from the host country affects foreign issuer’s subsequent IPO and post-IPO activities. Using a sample of foreign-listed Chinese firms, we find that the presence of pre-IPO shareholders from the host country is associated with a significant reduction in direct and indirect IPO costs, especially for issuers without international sales and for firms operating at a loss. Benefits of such pre-IPO affiliation persist into the post-IPO period as manifested in greater analyst coverage and better acquisition performance in the host country. Our paper provides new insight on the value of pre-IPO ownership diversification and identifies one strategy that firms can use to overcome the liability of foreignness.
Evidence for substantial genetic risk for psychopathy in 7-year-olds.

BACKGROUND Individuals with early warning signs of life-long psychopathy, callous-unemotional traits (CU) and high levels of antisocial behaviour (AB) can be identified in childhood. We report here the first twin study of high levels of psychopathic tendencies in young children. METHODS At the end of the first school year, teachers provided ratings of CU and AB for 3687 twin pairs from the Twins Early Development Study (TEDS). For the analyses of extreme CU, we selected same-sex twin pairs where at least one twin scored 1.3 or more standard deviations above the mean on the CU scale (612 probands, 459 twin pairs). For the analysis of extreme AB, we selected same-sex twin pairs where at least one twin scored 1.3 or more standard deviations above the mean on AB scale (444 probands, 364 twin pairs). Furthermore, the extreme AB sample was divided into those who were also extreme on CU (children with psychopathic tendencies; 234 probands, 187 twin pairs) and those who did not score in the extreme for CU (children without psychopathic tendencies; 210 probands, 177 twin pairs). RESULTS DeFries-Fulker extremes analysis indicated that exhibiting high levels of CU is under strong genetic influence. Furthermore, separating children with AB into those with high and low levels of CU showed striking results: AB in children with high levels of CU is under extremely strong genetic influence and no influence of shared environment, whereas AB in children with low levels of CU shows moderate genetic and shared environmental influence. CONCLUSIONS The remarkably high heritability for CU, and for AB children with CU, suggests that molecular genetic research on antisocial behaviour should focus on the CU core of psychopathy. Our findings also raise questions for public policy on interventions for antisocial behaviour.
Characterization of Rapid Membrane Internalization and Recycling*

Lipids and other membrane constituents recycle between the plasma membrane and intracellular endocytic compartments. In CHO cells, approximately half of the internalized C6-NBD-SM, a fluorescent lipid analogue widely used as a membrane maker, recycles via the endocytic recycling compartment with a t 1 2 of ∼12 min (Mayor, S., Presley, J. F., and Maxfield, F. R. (1993) J. Cell Biol. 121, 1257–1269). Surprisingly, the rest returns to the plasma membrane very quickly. A detailed kinetic study presented in this paper indicates that after a brief internalization pulse, 42–62% of the internalized C6-NBD-SM returns to the plasma membrane with a t 1 2 of 1–2 min. Similar results are obtained using HEp2 and nonpolarized Madin-Darby canine kidney cells. Using FM dyes of different hydrophobicity, we show that rapid recycling involves passage through an endocytic organelle that was subsequently identified as the sorting endosome by co-localization with internalized transferrin and low density lipoprotein. These results imply that the membrane internalization rate is much higher than previously estimated, with a t 1 2 as short as 5–10 min. Rapid internalization and recycling would facilitate processes such as nutrient uptake and cholesterol efflux.
Fifteen to Twenty Percent of HIV Substitution Mutations Are Associated with Recombination

ABSTRACT HIV undergoes high rates of mutation and recombination during reverse transcription, but it is not known whether these events occur independently or are linked mechanistically. Here we used a system of silent marker mutations in HIV and a single round of infection in primary T lymphocytes combined with a high-throughput sequencing and mathematical modeling approach to directly estimate the viral recombination and mutation rates. From >7 million nucleotides (nt) of sequences from HIV infection, we observed 4,801 recombination events and 859 substitution mutations (≈1.51 and 0.12 events per 1,000 nt, respectively). We used experimental controls to account for PCR-induced and transfection-induced recombination and sequencing error. We found that the single-cycle virus-induced mutation rate is 4.6 × 10−5 mutations per nt after correction. By sorting of our data into recombined and nonrecombined sequences, we found a significantly higher mutation rate in recombined regions (P = 0.003 by Fisher's exact test). We used a permutation approach to eliminate a number of potential confounding factors and confirm that mutation occurs around the site of recombination and is not simply colocated in the genome. By comparing mutation rates in recombined and nonrecombined regions, we found that recombination-associated mutations account for 15 to 20% of all mutations occurring during reverse transcription.