Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct roles of Wnt/β-catenin and Bmp signaling during early cardiogenesis

Heart formation requires the coordinated recruitment of multiple cardiac progenitor cell populations derived from both the first and second heart fields. In this study, we have ablated the Bmp receptor 1a and the Wnt effector β-catenin in the developing heart of mice by using MesP1-cre, which acts in early mesoderm progenitors that contribute to both first and second heart fields. Remarkably, the entire cardiac crescent and later the primitive ventricle were absent in MesP1-cre; BmpR1alox/lox mutants. Although myocardial progenitor markers such as Nkx2-5 and Isl1 and the differentiation marker MLC2a were detected in the small, remaining cardiac field in these mutants, the first heart field markers, eHand and Tbx-5, were not expressed. We conclude from these results that Bmp receptor signaling is crucial for the specification of the first heart field. In MesP1-cre; β-cateninlox/lox mutants, cardiac crescent formation, as well as first heart field markers, were not affected, although cardiac looping and right ventricle formation were blocked. Expression of Isl1 and Bmp4 in second heart field progenitors was strongly reduced. In contrast, in a gain-of-function mutation of β-catenin using MesP1-cre, we revealed an expansion of Isl1 and Bmp4 expressing cells, although the heart tube was not formed. We conclude from these results that Wnt/β-catenin signaling regulates second heart-field development, and that a precise amount and/or timing of Wnt/β-catenin signaling is required for proper heart tube formation and cardiac looping.
Distributed Submodular Maximization

Many large-scale machine learning problems (such as clustering, non-parametric learning, kernel machines, etc.) require selecting, out of a massive data set, a manageable yet representative subset. Such problems can often be reduced to maximizing a submodular set function subject to cardinality constraints. Classical approaches require centralized access to the full data set; but for truly large-scale problems, rendering the data centrally is often impractical. In this paper, we consider the problem of submodular function maximization in a distributed fashion. We develop a simple, two-stage protocol GREEDI, that is easily implemented using MapReduce style computations. We theoretically analyze our approach, and show, that under certain natural conditions, performance close to the (impractical) centralized approach can be achieved. In our extensive experiments, we demonstrate the effectiveness of our approach on several applications, including sparse Gaussian process inference and exemplar-based clustering, on tens of millions of data points using Hadoop.
R&D Productivity and Intellectual Property Rights Protection Regimes

We study firms' preferences towards intellectual property rights (IPR) regimes in a North-South context, using a simple duopoly model where a 'North' and a 'South' firm compete in a third market. Unlike other contributions in this field, we explicitly introduce the South's capability to undertake cost-reducing R&D, but maintain the South's inferiority in utilizing and managing its R&D. In contrast to traditional results, we show that the North may encourage lax IPR protection provided that its South rival's R&D productivity is sufficiently high, while the South may find it in its best interest to strictly enforce IPR protection if its R&D productivity is low. In this sense, our results do not support the idea of universal or uniform IPR protection regime. In addition, we find that if firms are allowed to agree on any level of information exchange when IPR protection is strictly enforced, such an exchange can always be established as long as each firm is ensured that what it gets to utilize in return is greater than a half of what it gives to its rival.
Global Burden of HIV among Men Who Engage in Transactional Sex: A Systematic Review and Meta-Analysis

Background Men who engage in transactional sex, the exchange of sex for money, goods, or other items of value, are thought to be at increased risk of HIV, but there have been no systematic attempts to characterize HIV burden in this population. We undertook a systematic review and meta-analysis to quantify the burden in this population compared with that of men in the general population to better inform future HIV prevention efforts. Methods We searched seven electronic databases, national surveillance reports, and conference abstracts for studies of men who engage in transactional sex published between 2004–2013. Random effects meta-analysis was used to determine pooled HIV prevalence and prevalence ratios (PR) for the difference in HIV prevalence among men who engage in transactional sex as compared to general population men. Findings Of 66 studies included representing 31,924 men who had engaged in transactional sex in 28 countries, pooled biological assay-confirmed HIV prevalence was 10.5% (95% CI = 9.4 to 11.5%). The highest pooled HIV prevalence was in Sub-Saharan Africa (31.5%, 95% CI = 21.6 to 41.5%), followed by Latin America (19.3%, 95% CI = 15.5 to 23.1%), North America (16.6%, 95% CI = 3.7 to 29.5%), and Europe (12.2%, 95% CI = 6.0 to 17.2%). Men who engaged in transactional sex had an elevated burden of HIV compared to the general male population (PR = 20.7, 95% CI = 16.8 to 25.5). Conclusions The global burden of HIV is disproportionately high among men who engage in transactional sex compared with the general male population. There is an urgent need to include this population in systematic surveillance as well as to scale-up access to quality HIV prevention programs.
Facial First Impressions Across Culture: Data-Driven Modeling of Chinese and British Perceivers’ Unconstrained Facial Impressions

People form first impressions from facial appearance rapidly, and these impressions can have considerable social and economic consequences. Three dimensions can explain Western perceivers’ impressions of Caucasian faces: approachability, youthful-attractiveness, and dominance. Impressions along these dimensions are theorized to be based on adaptive cues to threat detection or sexual selection, making it likely that they are universal. We tested whether the same dimensions of facial impressions emerge across culture by building data-driven models of first impressions of Asian and Caucasian faces derived from Chinese and British perceivers’ unconstrained judgments. We then cross-validated the dimensions with computer-generated average images. We found strong evidence for common approachability and youthful-attractiveness dimensions across perceiver and face race, with some evidence of a third dimension akin to capability. The models explained ~75% of the variance in facial impressions. In general, the findings demonstrate substantial cross-cultural agreement in facial impressions, especially on the most salient dimensions.
Estimating injury severity using the Barell matrix

Objective: To determine whether the Barell matrix (Inj Prev 2002;8:91–6) could effectively categorize injuries by severity. Methods: Injury diagnoses of cases in the 2002 US Nationwide Inpatient Sample were classified according to the Barell matrix. For each cell of the matrix, the authors used ICDMAP-90 to determine the predominant Abbreviated Injury Score (AIS) and body region, and calculated the weighted proportion surviving (bPScell) among patients with any diagnosis in that cell. These findings were used to estimate maximum AIS (bAISmax), ISS (bISS), and the minimum or product of bPScell (bPSmin, bPSprod) for injured patients in the 1996–2000 US National Hospital Discharge Surveys. Case survival was determined for different scores, and outcome models using age, sex, comorbidity, mechanism, and bISS or bPSmin were compared to models using ISS calculated from ICDMAP-90 (mISS) or using ICISS. Results: Case survival decreased with increasing bAISmax or bISS; survival was closely approximated by bPSmin, and also increased monotonically with bPSprod. Outcome models using bISS or bPSmin were similar to those using mISS or ICISS. An Abbreviated Barell Categorization, with only four groups, was also effective. Conclusion: Barell matrix categorization of administrative data allows severity scoring similar to that obtainable with ICDMAP-90 or ICISS.
Exploring Student Viewing Behaviors in Online Educational Videos

Online video use in education is an expanding trend and research that focuses on how students view educational videos becomes of particular interest. In our previous work, we argued that in order to conduct a detailed analysis of the learner viewing behavior we have to deploy tools that log the learner activity and assist statistical analysis and data mining. Working towards this direction, a framework for recording and analyzing learner behavior was presented. This paper presents findings of applying this framework into educational settings.
Diffusion Tensor Imaging of the Normal Foot at 3 T

Objective The objective of this study was to establish normative diffusion tensor imaging (DTI) eigenvalues (&lgr;1,&lgr;2,&lgr;3), apparent diffusion coefficient, and fractional anisotropy in asymptomatic foot muscles. Methods Ten healthy adults (mean [SD], 25.9 [4.3] years) were examined using a 3-T magnetic resonance imaging scanner. Diffusion tensor imaging indices were evaluated in 5 muscles in the foot: quadratus plantae, abductor hallucis, flexor hallucis brevis, flexor digitorum brevis, and abductor digiti minimi. Signal-to-noise ratio was also measured for each muscle. Results In the various foot muscles, &lgr;1 ranged from 1.88 × 10−3to 2.14 × 10−3 mm2/s, &lgr;2 ranged from 1.39 × 10−3 to 1.48 × 10−3 mm2/s, and &lgr;3 ranged from 0.91 × 10−3 to 1.27 × 10−3 mm2/s; apparent diffusion coefficient ranged from 1.48 × 10−3 to 1.55 × 10−3 mm2/s; and fractional anisotropy ranged from 0.21 to 0.40. Statistical differences were seen in some eigenvalues between muscle pairs. Mean signal-to-noise ranged from 47.5 to 69.1 in the various muscles examined. Conclusions Assessment of anisotropy of water diffusion in foot muscles was feasible using DTI. The measured DTI metrics in the foot were similar to those in calf and thigh skeletal muscles.
Polymer-embedded colloidal lead-sulfide nanocrystals integrated to vertically slotted silicon-based ring resonators for telecom applications

Abstract. The main drawback of the rapidly evolving field of silicon photonics lies in the absence of efficient monolithically integrated radiation sources as a consequence of the indirect bandgap of Si and Ge. Relevant alternatives based on the hybrid combination of Si with optically active materials have to be technologically simple, temporally stable, and provide efficient coupling to the Si waveguides. Lead-sulfide nanocrystals (NCs) were blended into a polymer resist suitable for deep-UV- and electron-beam lithography and integrated into Si-based vertically slotted waveguides and ring resonators. The polymer both stabilizes the NC’s photoluminescence emission against degradation under ambient conditions and allows lithographic patterning of this compound material. After integration into the optoelectronic structures and upon optical pumping, intense photoluminescence emission from ring resonators was recorded at the output of bus-waveguides. The resonator quality factors were investigated for polymer-NC compounds with NC concentrations in the range between 0.1 and 8 vol%. The spontaneous emission rate enhancement for vertically slotted resonators was estimated to be a factor of two higher as compared to unslotted ones. The stable integration of colloidal NCs as well as the improved light coupling to silicon circuits is an important step in the development of silicon-based hybrid photonics.
Angiotensin converting enzyme inhibition unmasks the sympathofacilitatory effect of bradykinin in human right atrium

Objective To investigate the role of angiotensin converting enzyme (ACE) inhibition in bradykinin-mediated modulation of noradrenaline release in human and rat atrium. Methods Human and rat atrial slices were incubated with [3H]-noradrenaline, superfused with Krebs–Henseleit solution and stimulated electrically at 5 Hz. The stimulation-induced outflow of radioactivity was taken as an index of endogenous noradrenaline release. Results In the absence of ACE inhibition 0.01–1 μmol/l bradykinin failed to alter the release of noradrenaline in human atrium. In contrast, 0.001–0.1 μmol/l bradykinin enhanced the release of noradrenaline in rat atrium. In the presence of 3 μmol/l of the ACE inhibitor captopril, however, bradykinin significantly enhanced the release of noradrenaline in human atrium. The bradykinin B1-receptor agonist (Des-Arg9)-bradykinin (0.01–1 μmol/l) had no effect on the release of noradrenaline in human atrium both in the absence and in the presence of 3 μmol/l captopril. Captopril (3 μmol/l) potentiated the facilitatory effect of bradykinin in rat atrium. The selective bradykinin B2-receptor antagonist D-Arg[Hyp3, Thi5, D-Tic7,Oic8]-bradykinin (Hoe 140, 0.3 μmol/l) and the cyclo-oxygenase inhibitor indomethacin (10 μmol/l) reduced the facilitatory effect of bradykinin significantly in the presence of captopril in rat and human atrium. Prostaglandin F2α (0.1 μmol/l), prostaglandin E2 (0.3 μmol/l) and the thromboxane A2 receptor agonist U-46 619 (0.1 μmol/l) enhanced the release of noradrenaline in human atria, whereas 0.1 μmol/l prostaglandin I2 had no effect. Conclusion These data suggest that bradykinin facilitates the release of noradrenaline in human and rat atrium by activation of bradykinin receptors of the B2-subtype and subsequent release of facilitatory prostaglandins. The facilitatory effect of bradykinin in human atrium can only be demonstrated when its enzymatic degradation is prevented by ACE inhibition.
The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study

R-Bendamustine is an effective treatment for follicular lymphoma (FL). Previous large trials demonstrated the prognostic role of the molecular minimal residual disease (MRD) during the most frequently adopted chemotherapeutic regimens, but there are not yet conclusive data about the effect of combination of rituximab (R) and bendamustine in terms of MRD clearance. Thus, the aim of this retrospective study was to assess if and in what extent the combination of rituximab and bendamustine would exert a significant reduction of the molecular disease in 48 previously untreated FL patients. The molecular marker at baseline was found in the 62.5% of cases; no significant differences were observed between patients with or without the molecular marker in respect of the main clinical features. Moreover, the quantization of the baseline molecular tumor burden showed a great variability: the median value was 1.4 × 10−2 copies, ranging from 3 × 10−5 to 4 × 104. The initial molecular tumor burden did not correlate with clinical features and did not impact on the subsequent quality of response. After treatment, 93% of cases became MRD-negative; the median reduction of the BCL2/JH load was 4 logs. The 2-years PFS was 85%; it was significantly longer for patients in complete than for those in partial response (91 vs. 57%; p = 0.002), and for cases with lower FLIPI-2 score (88 vs. 60%; p = 0.004). On the contrary, PFS did not differ between patients with or without the molecular marker at baseline; a molecular tumor burden 15 times higher was observed in the relapsed subgroup in comparison to the relapse-free one, but this difference did not change the PFS length. The 2-years OS was 93.6%; the only variable that significantly impacted on it was the FLIPI-2 score; the presence of the molecular marker at baseline or its behavior after treatment did not impact on survival. This study, even if retrospective and conducted on a small series of patients, would represent a proof of concept that R-bendamustine is able to so efficaciously eradicate MRD that it could be able to by-pass the prognostic significance of MRD already demonstrated for other chemotherapeutic regimens in FL.
Impact of Different Analytic Approaches on the Analysis of the Breast Fibroglandular Tissue Using Diffusion Weighted Imaging

Purpose. This study investigated the impact of the different region of interest (ROI) approaches on measurement of apparent diffusion coefficient (ADC) values in the breast firbroglandular tissue (FT). Methods. Breast MR images of 38 women diagnosed with unilateral breast cancer were studied. Percent density (PD) and ADC were measured from the contralateral normal breast. Four different ROIs were used for ADC measurement. The measured PD and ADC were correlated. Results. Among the four ROIs, the manually placed small ROI on FT gave the highest mean ADC (ADC = 1839 ± 343 [×10−6 mm2/s]), while measurement from the whole breast gave the lowest mean ADC (ADC = 933 ± 383 [×10−6 mm2/s]). The ADC measured from the whole breast was highly correlated with PD with r = 0.95. In slice-to-slice comparison, the central slices with more FT had higher ADC values than the peripheral slices did, presumably due to less partial volume effect from fat. Conclusions. Our results indicated that the measured ADC heavily depends on the composition of breast tissue contained in the ROI used for the ADC measurements. Women with low breast density showing lower ADC values were most likely due to the partial volume effect of fatty tissues.
p 53 promotes inflammation-associated hepatocarcinogenesis by inducing HMGB 1 release

Background & Aims: Hepatocellular carcinoma (HCC) develops in response to chronic hepatic injury. Although induced cell death is regarded as the major component of p53 tumor-suppressive activity, we recently found that sustained p53 activation subsequent to DNA damage promotes inflammation-associated hepatocarcinogenesis. Here we aim at exploring the mechanism linking p53 activation and hepatic inflammation during hepatocarcinogenesis. Methods: p53 / hepatocytes expressing inducible p53 and primary wild type hepatocytes were treated to induce p53 expression. The supernatants were collected and analyzed for the presence of released inflammatory cytokines. Ethyl pyruvate was used in a rat model of carcinogen-induced hepatocarcinogenesis to examine its effect on p53-dependent chronic hepatic injury, inflammation, and tumorigenesis. Results: Here we show that cytoplasmic translocation and circulating levels of potent inflammatory molecule high-mobility group protein 1 (HMGB1) were greater in wild type rats than in p53 rats following carcinogen administration. Restoration of p53 expression in p53-null hepatocytes or induction of endogenous p53 in wild type hepatocytes gives rise to the release of HMGB1. Administration of the HMGB1 release inhibitor ethyl pyruvate, which does not affect p53-mediated hepatic apoptosis, substantially prevented carcinogen-induced cirrhosis and tumorigenesis in rat livers. Conclusions: These results suggest that although p53 is usually regarded as a tumor suppressor, its constant activation can promote pro-tumorigenic inflammation, at least in part, via inducing HMGB1 release. Application of HMGB1 inhibitors when restoring p53 in cancer therapy might protect against pro-tumorigenic effects while leaving p53-mediated clearance of malignant cells intact.
Enhancing bone healing and regeneration: present and future perspectives in veterinary orthopaedics

Summary Methods currently used to restore bone defects in human and veterinary orthopaedics are often not satisfactory. This is especially the case in the healing of large, irregular defects which result in the formation of tissues with inferior qualities compared to the original structures. For these reasons, several new approaches are currently being explored to improve bone healing capacities in different situations. This review will examine the different techniques used to enhance bone regeneration, highlighting both experimental and clinically applicable methods with regard to veterinary orthopaedics.
Global Asymptotic Behavior of a Chemostat Model with Two Perfectly Complementary Resources and Distributed Delay

A model of the chemostat involving two species of microorganisms competing for two perfectly complementary, growth-limiting nutrients is considered. The model incorporates distributed time delay in the form of integral differential equations in order to describe the time involved in converting nutrient to biomass. The delays are included in the nutrient and species concentrations simultaneously. A general class of monotone increasing functions is used to describe nutrient uptake. Sufficient conditions based on biologically meaningful parameters in the model are given that predict competitive exclusion for certain parameter ranges and coexistence for others. We prove that the global asymptotic attractivity of steady states of the model is similar to that of the corresponding model without time delays. However, our results indicate that when the inherent delays are in fact large, ignoring them may result in incorrect predictions.
Does dementia increase risk of thrombolysis?

Background: Dementia represents a potential challenge when thrombolysis is a treatment option. In this study, we assess the impact of dementia on the rate of intracerebral hemorrhage (ICH) and hospital mortality associated with acute ischemic stroke (AIS) in patients treated with thrombolysis. Methods: A cohort of patients with AIS was identified from the National Inpatient Sample database for the years 2000 to 2007. Vascular and degenerative types of dementia were identified by the International Classification of Diseases–9-CM codes. A matched random sample without dementia was selected from a pool of those with AIS and treated with thrombolysis. Results: In this analysis, 35,557 patients with diagnosis of dementia were included; 207 (0.56%) received thrombolysis. In-hospital mortality (17.48% vs 8.63%) and ICH (5.80% vs 0.38%) were higher in the thrombolysis group (p < 0.0001) compared to those who did not receive thrombolysis. Multivariate analysis showed that thrombolysis was associated with increased hospital mortality (odds ratio [OR] 16.15; 95% confidence interval [CI] 8.54–30.53) and ICH (OR 2.80; 95% CI 1.82–4.32). Compared to a matched population of patients without dementia treated with thrombolysis (n = 621), those who had dementia and were treated with thrombolysis had similar risks of ICH (5.80% vs 4.51%, p = 0.45) and mortality (17.39% vs 14.49%, p = 0.31) rates. With thrombolysis, ICH remained a predictor of mortality for both dementia and control groups (OR 2.25; 95% CI 1.02–4.99). Conclusion: The administration of thrombolysis for AIS in patients with dementia was not associated with increased risk of ICH or death compared to the counterparts without dementia. ICH remained as predictor of mortality.
Stability analysis for interconnected systems with “mixed” passivity, negative-imaginary and small-gain properties

An analytical framework to examine the finite-gain stability for a positive feedback interconnection between two stable, linear time-invariant systems where one system has “mixed” passivity, negative-imaginary and small-gain properties and the other system has “mixed” negative-imaginary, negative-passivity, and small-gain properties is proposed. A classical Nyquist argument is used to examine the stability of the interconnected systems and the usefulness of the proposed framework is illustrated by a numerical example.