Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving procedural and one-year outcome after contact force-guided pulmonary vein isolation: the role of interlesion distance, ablation index, and contact force variability in the 'CLOSE'-protocol.

Aims We have recently shown that a contact force (CF)-guided ablation protocol respecting region-specific criteria of lesion contiguity and lesion depth ('CLOSE' protocol) is associated with high incidence of acute durable pulmonary vein (PV) isolation (PVI) and a high single-procedure arrhythmia-free survival at 1 year. In the present study, we compared efficiency, safety, and efficacy of 'CLOSE'-guided PVI to conventional CF-guided PVI (CONV-CF). Methods and results Fifty consecutive paroxysmal atrial fibrillation (AF) patients underwent PV encircling using a CF-sensing catheter targeting an interlesion distance (ILD) ≤6 mm and ablation index (AI) ≥400 and ≥550 at posterior and anterior wall ('CLOSE' group). Results were compared to the last 50 patients undergoing 'CONV-CF'. All patients underwent adenosine testing after PVI. Arrhythmia recurrence was defined as any atrial tachyarrhythmia (ATA) >30 s on Holter at 3, 6, and 12 months. Clinical characteristics did not differ. Contact force variability was comparable in between both groups (proportion of applications with intermittent contact 2% in 'CLOSE' vs. 1% in CONV-CF, P = 0.67). In the 'CLOSE' group, procedure time and radiofrequency (RF) time per circle were shorter (respectively 149 ± 33 min vs. 192 ± 42 min, P < 0.0001 and 18 ± 4 min vs 28 ± 7.5 min, P < 0.0001) and incidence of adenosine-proof isolation was higher (97% vs. 82%, P < 0.001). No complications were observed in the 'CLOSE' group, one tamponade in the 'CONV-CF' group. At 12 months, single-procedure freedom from ATA was 94% in 'CLOSE' vs. 80% in 'CONV-CF' group (P < 0.05). In both groups, the majority of reconnections at repeat were associated with either ILD > 6 mm and/or AI < 400/550 (100% vs. 83%, P = 0.99). Conclusion 'CLOSE'-guided PVI improves procedural and 1 year outcome in CF-guided PVI while shortening procedure time. Improvement cannot be explained by differences in CF variability and is most likely due to the strict application of criteria for contiguity and ablation index. A randomized controlled trial is needed to exclude the possible contribution of a learning curve.
Graphite–graphene hybrid filler system for high thermal conductivity of epoxy composites

The thermal conductivities of epoxy composites of mixtures of graphite and graphene in varying ratios were measured. Thermal characterization results showed unexpectedly high conductivities at a certain ratio filler ratio. This phenomenon was exhibited by samples with three different overall filler concentrations (graphene + graphite) of 7, 14, and 35 wt%. The highest thermal conductivity of 42.4 ± 4.8 W/m K (nearly 250 times the thermal conductivity of pristine epoxy) was seen for a sample with 30 wt% graphite and 5 wt% graphene when characterized using the dual-mode heat flow meter technique. This significant improvement in thermal conductivity can be attributed to the lowering of overall thermal interface resistance due to small amounts of nanofillers (graphene) improving the thermal contact between the primary microfillers (graphite). The synergistic effect of this hybrid filler system is lost at higher loadings of the graphene relative to graphite. Graphite and graphene mixed in the ratio of 6:1 yielded the highest thermal conductivities at three different filler loadings.
Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients

VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined. We found that rs9582036 and rs9554320 showed a significant association with sunitinib PFS in the CCF cohort (HR: 0.254, 95%CI: 0.092-0.703; P=0.008 and HR: 0.430, 95%CI: 0.200-0.927; P=0.031, respectively). Patients with the variant genotype of rs9582036 and rs9554320 had a shorter median PFS. No significant association of both SNPs with sunitinib PFS or OS was detected in either the SUTOX or SOGUG cohort. After the combination of all available data into a meta-analysis, the association of both SNPs with sunitinib PFS or OS did not achieve the threshold for statistical significance. Our findings suggest that, although VEGFR1 rs9582036 and rs9554320 are involved in sunitinib therapy outcome, its clinical use as biomarkers for prediction of sunitinib outcome in mRCC patients is limited, due to inconsistent findings when analyzing all existing studies together.
Credit‐Constrained in Risky Activities? The Determinants of the Capital Stocks of Micro and Small Firms in Western Africa

Micro and Small Enterprises (MSEs) in developing countries are typically considered to be severely credit constrained. Additionally, high business risks may partly explain why capital stocks of MSEs remain low. This article analyzes the determinants of capital stocks of MSEs in poor economies focusing on credit constraints and risk. The analysis is based on a unique, albeit cross sectional but backward looking, micro data set on MSEs covering the economic capitals of seven West-African countries. The main result is that capital market imperfections indeed seem to explain an important part of the variation in capital stocks in the early lifetime of MSEs. Furthermore, the analyses show that risk plays a key role for capital accumulation. Risk-averse individuals seem to adjust their initially low capital stocks upwards when enterprises grow older. MSEs in risky activities owned by wealthy individuals even seem to over-invest when they start their business and adjust capital stocks downwards subsequently. As other firms simultaneously suffer from capital shortages, such behavior may imply large inefficiencies.
Floral morphology and anatomy of Ophiocaryon, a paedomorphic genus of Sabiaceae

Background and Aims Ophiocaryon is a lesser known genus in Sabiaceae. This study examines flowers of six Ophiocaryon species in comparison with Meliosmaalba, to identify taxonomically informative characters for understanding relationships within the family Sabiaceae, to imply previously unknown pollination mechanisms of Ophiocaryon, and to contribute to the placement of Sabiaceae within the early-diverging eudicots. Methods Floral morphology and anatomy of six Ophiocaryon species and M. alba were studied and described using scanning electron microscopy, clearing techniques and resin sectioning. Key Results Novel characters of Ophiocaryon were identified, e.g. conical cells on petals, different kinds of orbicules in anthers, stomata on nectary appendage tips and ovary, two distinct surface patterns on stamens and ovary, tanniferous cell layers in the ovary wall, and acorn-shaped unitegmic ovules with very short integuments. Comparison of floral characters between Ophiocaryon and Meliosma found that the calyx, corolla, androecium and gynoecium of Ophiocaryon resemble an undeveloped state of the latter taxon, reflecting a paedomorphic regression of the flower of Ophiocaryon. The flower morphology and anatomy of Ophiocaryon was compared with its putative sister species M. alba, but no clear shared derived characters could be detected. Moreover, the findings of scent, presence of conical cells on petals and a nectary suggest flowers are pollinated by small insects with a secondary pollen presentation on the cupula of fertile stamens. Conclusions We found that Ophiocaryon may be derived from ancestors that were similar to extant Meliosma in their flower structure and pollination mechanism. However, the lack of shared derived characters between Ophiocaryon and its phylogenetic sister group M. alba is puzzling and requires further investigations on the diversity of the latter species.
Energy-efficient redundant execution for chip multiprocessors

Relentless CMOS scaling coupled with lower design tolerances is making ICs increasingly susceptible to wear-out related permanent faults and transient faults, necessitating on-chip fault tolerance in future chip microprocessors (CMPs). In this paper, we describe a power-efficient architecture for redundant execution on chip multiprocessors (CMPs) which when coupled with our per-core dynamic voltage and frequency scaling (DVFS) algorithm significantly reduces the energy overhead of redundant execution without sacrificing performance. Our evaluation shows that this architecture has a performance overhead of only 0.3% and consumes only 1.48 times the energy of a non-fault-tolerant baseline.
Concurrent and Longitudinal Associations Among Temperament, Parental Feeding Styles, and Selective Eating in a Preschool Sample

Objective To examine the associations among negative/reactive temperament, feeding styles, and selective eating in a sample of preschoolers because preschool eating behaviors likely have lasting implications for children's health. Methods A community sample of preschoolers aged 3-5 years (M = 4.49 years, 49.5% female, 75.7% European American) in the Midwest of the United States was recruited to participate in the study (N = 297). Parents completed measures of temperament and feeding styles at two time points 6 months apart. Results A series of regressions indicated that children who had temperaments high in negative affectivity were significantly more likely to experience instrumental and emotional feeding styles. They were also significantly more likely to be selective eaters. These associations were present when examined both concurrently and after 6 months. Conclusions This study provides a novel investigation of child temperament and eating behaviors, allowing for a better understanding of how negative affectivity is associated with instrumental feeding, emotional feeding, and selective eating. These results inform interventions to improve child health.
Blockholders and Corporate Governance

This paper reviews the theoretical and empirical literature on the channels through which blockholders (large shareholders) engage in corporate governance. In classical models, blockholders exert governance through direct intervention in a firm’s operations, otherwise known as “voice. ” These theories have motivated empirical research on the determinants and consequences of activism. More recent models show that blockholders can govern through an alternative mechanism known as “exit”—selling their shares if the manager underperforms. These theories give rise to new empirical studies on the two-way relationship between blockholders and financial markets, linking corporate finance with asset pricing. Blockholders may also worsen governance by extracting private benefits of control or pursuing objectives other than firm value maximization. I highlight the empirical challenges in identifying causal effects of and on blockholders as well as the typical strategies attempted to achieve identification. I close with directions for future research.
Xylogenesis reveals the genesis and ecological signal of IADFs in Pinus pinea L. and Arbutus unedo L.

Background and Aims Mediterranean trees have patterns of cambial activity with one or more pauses per year, leading to intra-annual density fluctuations (IADFs) in tree rings. We analysed xylogenesis (January 2015-January 2016) in Pinus pinea L. and Arbutus unedo L. , co-occurring at a site on Mt. Vesuvius (southern Italy), to identify the cambial productivity and timing of IADF formation. Methods Dendrochronological methods and quantitative wood anatomy were applied and enabled IADF identification and classification. Key Results We showed that cambium in P. pinea was productive throughout the calendar year. From January to March 2015, post-cambial (enlarging) earlywood-like tracheids were observed, which were similar to transition tracheids. The beginning of the tree ring was therefore not marked by a sharp boundary between latewood of the previous year and the new xylem produced. True earlywood tracheids were formed in April. L-IADFs were formed in autumn, with earlywood-like cells in latewood. In A. unedo, a double pause in cell production was observed, in summer and winter, leading to L-IADFs in autumn as well. Moreover, the formation of more than one IADF was observed in A. unedo. Conclusions Despite having completely different wood formation models and different life strategies, the production of earlywood, latewood and IADF cells was strongly controlled by climatic factors in the two species. Such cambial production patterns need to be taken into account in dendroecological studies to interpret climatic signals in wood from Mediterranean trees.
Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer

Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors. In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies. In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05). The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%). Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.
Utility of Model‐Based Approaches for Informing Dosing Recommendations in Specific Populations: Report From the Public AAPS Workshop

This report summarizes the discussions and recommendations of the workshop titled “Specific Population Drug Dosing Recommendations: Shifting from Clinical Studies to Predict and Confirm,” which preceded the 2015 American Association of Pharmaceutical Scientists annual meeting. Participants from the pharmaceutical industry, regulatory agencies (FDA and EMA), and academia discussed the current state, challenges, opportunities, and future direction of utilizing model‐based approaches to inform dosing recommendations in specific populations.
An Empirical Survey of Individual Consumer, Business Firm and Financial Institution Attitudes towards Islamic Methods of Finance

Purpose - The purpose of this paper is to review the attitudes, perceptions and knowledge of Islamic financial products and services. Design/methodology/approach - A synoptic survey of empirical analyses about Islamic financial products and services and comparison with the literature on conventional financial services and products. Findings - It was found that while religious conviction is a key factor in the use of Islamic finance, consumers also identify bank reputation, service quality and pricing as being of relevance. When selecting a financial institution's products and services, business firms usually employ criteria that are more conventional, such as the cost of finance, in their decision making. There is also interest among financial institutions in supplying Islamic financial products and services, but this is mitigated by complications with firm management and a lack of familiarity with business conditions. The concept of risk sharing with borrowers serves as a substantial barrier to most financial institutions engaging in Islamic methods of finance. Practical implications - Need for further theoretical and empirical research on how religious convictions affect consumers in their financial decision making. In addition, most work on Islamic finance is in a single national context, international comparisons are required. Originality/value - This paper is the only known empirical survey of attitudes, perceptions and knowledge of Islamic financial products and services. It provides guidance for future research in Islamic finance and serves as an aid for decision making by policymakers, consumer interest groups, business firms and financial institutions.
Incorporating problem based learning into medical curriculum: An experience from a medical college in Mangalore

BACKGROUND: The Medical Council of India (MCI) has envisioned a change in the undergraduate medical curriculum by encouraging integrated teaching and Problem Based Learning (PBL). METHODS: In this cross-sectional study 110 medical teachers of Kasturba Medical College, Mangalore were assessed regarding their perception on PBL. Independent t-test was applied to find out the difference in the mean perception scores regarding PBL among the teachers in pre/para-clinical and clinical departments and P < 0.05 was considered statistically significant. RESULTS: PBL as a teaching method was preferred by 65.2% medical teachers. The teachers from clinical departments (Mean 4.1, SD 0.8) perceived PBL sessions to be more effective than the traditional methods than those from the pre-clinical and para clinical departments (Mean 3.7, SD 3.7) and this difference was found to be statistically significant. (P =0.028). CONCLUSION: PBL can complement integrated teaching and motivates students towards self-learning, and apply the learnt concepts of basic specialties to clinical problem solving.
Nuclear Import of JAK1 Is Mediated by a Classical NLS and Is Required for Survival of Diffuse Large B-cell Lymphoma

JAKs are non-receptor tyrosine kinases that are generally found in association with cytokine receptors. In the canonical pathway, roles of JAKs have well been established in activating STATs in response to cytokine stimulation to modulate gene transcription. In contrast, a noncanonical role of JAK2 has recently been discovered, in which JAK2 in the nucleus imparts the epigenetic regulation of gene transcription through phosphorylation of tyrosine 41 on the histone protein H3. Recent work further demonstrated that this noncanonical mechanism is conserved with JAK1, which is activated by the autocrine cytokines IL6 and IL10 in activated B-cell–like diffuse large B-cell lymphoma (ABC DLBCL), a cancer type that is particularly difficult to treat and has poor prognosis. However, how JAK1 gains access to the nucleus to enable epigenetic regulation remains undefined. Here, we investigated this question and revealed that JAK1 has a classical nuclear localization signal toward the N-terminal region, which can be recognized by multiple importin α isoforms. Moreover, the nuclear import of JAK1 is independent of its kinase activity but is required for the optimal expansion of ABC DLBCL cells in vitro. Implications: This study demonstrates that the nuclear import of JAK1 is essential for the optimal fitness of ABC DLBCL cells, and targeting JAK1 nuclear localization is a potential therapeutic strategy for ABC DLBCL. Mol Cancer Res; 15(3); 348–57. ©2016 AACR.
Influence of the Barotropic Mean Flow on the Width and the Structure of the Atlantic Equatorial Deep Jets

A representation of an equatorial basin mode excited in a shallow water model for a single high order baroclinic vertical normal mode is used as a simple model for the equatorial deep jets. The model is linearized about both a state of rest and a barotropic mean flow corresponding to the observed Atlantic Equatorial Intermediate Current System. We found that the eastward mean flow associated with the North and South Intermediate Counter Currents (NICC and SICC, respectively) effectively shields the Equator from off-equatorial Rossby waves. The westward propagation of these waves is blocked and focusing on the Equator due to beta dispersion is prevented. This leads to less energetic jets along the Equator. On the other hand, the westward barotropic mean flow along the Equator reduces the gradient of absolute vorticity and hence widens the cross-equatorial structure of the basin mode. Increasing lateral viscosity predominantly affects the width of the basin modes’ Kelvin wave component in the presence of the mean flow while the Rossby wave is confined by the flanking NICC and SICC. Independent of the presence of the mean flow, the application of sufficient lateral mixing also hinders the focusing of off-equatorial Rossby waves, which is hence an unlikely feature of a low-frequency basin mode in the real ocean.
Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells

Interleukin 33 (IL-33), an inflammatory and mechanically responsive cytokine, is an important component of a TLR4-dependent innate immune process in mucosal epithelium. Although TLR4 also plays a role in sensing biomechanical stretch, a pathway of stretch-induced TLR4-dependent IL-33 biosynthesis has not been revealed. In the current study, we show that short term (6 h) cyclic stretch (CS) of cultured murine respiratory epithelial cells (MLE-12) increased intracellular IL-33 expression in a TLR4 dependent fashion. There was no detectable IL-33 in conditioned media in this interval. CS, however, increased release of the notable alarmin, HMGB1, and a neutralizing antibody (2G7) to HMGB1 completely abolished the CS mediated increase in IL-33. rHMGB1 increased IL-33 synthesis and this was partially abrogated by silencing TLR4 suggesting additional receptors for HMGB1 are involved in its regulation of IL-33. Collectively, these data reveal a HMGB1/TLR4/IL-33 pathway in the response of respiratory epithelium to mechanical stretch.
Comparative Proteomic Analysis of Plant Acclimation to Six Different Long-Term Environmental Changes

Plants are constantly challenged in their natural environment by a range of changing conditions. We investigated the acclimation processes and adaptive plant responses to various long-term mild changes and compared them directly within one experimental set-up. Arabidopsis thaliana plants were grown in hydroponic culture for 10 d under controlled abiotic stress (15°C, 25°C, salt and osmotic) and in nutrient deficiency (nitrate and phosphate). Plant growth was monitored and proteomic experiments were performed. Resource allocation between tissues altered during the plants' response. The growth patterns and induced changes of the proteomes indicated that the underlying mechanisms of the adaptation processes are highly specific to the respective environmental condition. Our results indicated differential regulation of response to salt and osmotic treatment, while the proteins in the changed temperature regime showed an inverse, temperature-sensitive control. There was a high correlation of protein level between the nutrient-deficient treatments, but the enriched pathways varied greatly. The proteomic analysis also revealed new insights into the regulation of proteins specific to the shoot and the root. Our investigation revealed unique strategies of plant acclimation to the different applied treatments on a physiological and proteome level, and these strategies are quite distinct in tissues below and above ground.