Miracle-dz/UniFAR-FTUs huggingface dataset:
Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes

Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.
Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to Risk Alleles for Coronary Artery Disease in the General Population

Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single‐nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD.
International Journal of Nanomedicine Dovepress Functionalization of Carboxylated Multiwall Nanotubes with Imidazole Derivatives and Their Toxicity Investigations

Imidazoles and their derivatives are compounds with chemotherapeutic applications. In this study, we investigated the chemical functionalization of carboxylated multiwalled carbon nanotubes (MWNT–COOH) by 1,2-phenylendiamine. Multiwalled nanotube (MWNT)–benzimidazole was obtained by an MWNT–amide reaction with POCl 3 after 72 hours, which was confirmed by Fourier transform infrared, scanning electron microscopy, thermal gravimetric analysis, and elemental analysis. These functionalizations were chosen due to-NH 2 and NHCO active sites in MWNT–amide for future application. Toxicity assays with fibroblast cells and MTT test for measurement of viable cell numbers were also performed. Cellular results did not show any toxicity change in modified samples from that of the reference samples.
Towards Cooperation in Sequential Prisoner's Dilemmas: a Deep Multiagent Reinforcement Learning Approach

The Iterated Prisoner's Dilemma has guided research on social dilemmas for decades. However, it distinguishes between only two atomic actions: cooperate and defect. In real-world prisoner's dilemmas, these choices are temporally extended and different strategies may correspond to sequences of actions, reflecting grades of cooperation. We introduce a Sequential Prisoner's Dilemma (SPD) game to better capture the aforementioned characteristics. In this work, we propose a deep multiagent reinforcement learning approach that investigates the evolution of mutual cooperation in SPD games. Our approach consists of two phases. The first phase is offline: it synthesizes policies with different cooperation degrees and then trains a cooperation degree detection network. The second phase is online: an agent adaptively selects its policy based on the detected degree of opponent cooperation. The effectiveness of our approach is demonstrated in two representative SPD 2D games: the Apple-Pear game and the Fruit Gathering game. Experimental results show that our strategy can avoid being exploited by exploitative opponents and achieve cooperation with cooperative opponents.
Doppler Spread Estimation in MIMO Frequency-Selective Fading Channels

One of the main challenges in high-speed mobile communications is the presence of large Doppler spreads. Thus, accurate estimation of maximum Doppler spread (MDS) plays an important role in improving the performance of the communication link. In this paper, we derive the data-aided (DA) and non-data-aided (NDA) Cramér–Rao lower bounds (CRLBs) and maximum likelihood estimators (MLEs) for the MDS in multiple-input multiple-output (MIMO) frequency-selective fading channel. Moreover, a low-complexity NDA-moment-based estimator (MBE) is proposed. The proposed NDA-MBE relies on the second- and fourth-order moments of the received signal, which are employed to estimate the normalized squared autocorrelation function of the fading channel. Then, the problem of MDS estimation is formulated as a non-linear regression problem, and the least-squares curve-fitting optimization technique is applied to determine the estimate of the MDS. This is the first time in the literature, when DA- and NDA-MDS estimation is investigated for MIMO frequency-selective fading channel. Simulation results show that there is no significant performance gap between the derived NDA-MLE and NDA-CRLB, even when the observation window is relatively small. Furthermore, the significant reduced-complexity in the NDA-MBE leads to low root-mean-square error over a wide range of MDSs, when the observation window is selected large enough.
Attachment and emotional understanding in preschool children.

This study was designed to elucidate the association between attachment and emotional understanding in preschool children. Forty children between the ages of 2.5 and 6 years and their mothers participated in the study. Mothers completed the Attachment Q-set, and children took part at their preschools in both an affective perspective-taking task and a series of interviews concerning naturally occurring incidents of emotions. Overall, age and attachment security predicted a child's aggregate score on the emotional understanding tasks. However, when the score was separated by the valence of the emotion, attachment security and age predicted a child's score for only those emotions with a negative valence (e.g., sadness) and not for those emotions with a positive valence (e.g., happiness). Thus, a secure attachment relationship seems to be important in fostering a child's understanding of emotion, primarily negative emotions.
Postoperative Inflammation After Endoscopic Cyclophotocoagulation: Racial Distribution and Effect on Outcomes

Purpose: To assess the prevalence of postoperative anterior chamber reaction or persistent anterior uveitis (PAU) by race and its effect on intraocular pressure (IOP) and visual acuity (VA) after combined phacoemulsification and endoscopic cyclophotocoagulation (ECP) in primary open-angle glaucoma. Patients and Methods: A retrospective analysis of all patients with primary open-angle glaucoma who underwent combined phacoemulsification cataract extraction with ECP from January 1, 2007 to October 31, 2015. VA, IOP, presence of anterior chamber cells, steroid treatment, and number of IOP lowering drops were analyzed preoperatively and up to 3 months postoperatively. Patients were categorized according to self-reported race. PAU was treated according to severity and presence of symptoms. Results: Two hundred twenty-three eyes met the inclusion criteria. PAU was present in 22.4% of eyes. PAU was significantly correlated with race, particularly African American race. PAU was also associated with a lack of improvement in inflammation at week 1 compared with day 1 postoperatively. However, there was no significant difference in VA, IOP, or reduction of IOP lowering drops in those with or without PAU. When comparing African Americans to whites, PAU and its treatment were not associated with a difference in IOP reduction at 3 months. Conclusions: PAU is common after combined phacoemulsification and ECP and is significantly correlated with race. Although PAU may require prolonged postoperative treatment, our data does not support poorer VA or IOP outcomes.
Intravoxel incoherent motion: application in differentiation of hepatocellular carcinoma and focal nodular hyperplasia.

PURPOSE We aimed to explore whether intravoxel incoherent motion (IVIM)-related parameters of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) demonstrate differences that could be used to differentiate and improve diagnostic efficiency. METHODS A total of 27 patients, including 22 with HCC and 5 with FNH, underwent liver 3.0 T magnetic resonance imaging for routine sequences. They were concurrently examined by IVIM diffusion-weighted imaging (DWI) scanning with 11 different b values (0-800 s/mm2). IVIM-derived parameters, such as pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADCtotal), were quantified automatically by post-processing software and compared between HCC and FNH groups. A receiver operating characteristic (ROC) curve was then created to predict their diagnostic value. RESULTS D* was weak in terms of reproducibility among the other parameters. ADCtotal, D, and D* were significantly lower in the HCC group than in the FNH group, while f did not show a significant difference. ADCtotal and D had the largest area under the curve values (AUC; 0.915 and 0.897, respectively) and similarly high efficacy to differentiate the two conditions. CONCLUSION IVIM provides a new modality to differentiate the HCC and FNH. ADCtotal and D demonstrated outstanding and comparable diagnosing utility.
Changes in pulmonary arterial and femoral arterial blood pressure upon acute exposure to hypobaric hypoxia in broiler chickens.

An experiment was conducted to investigate the pulmonary arterial and femoral arterial pressure responses to acute hypobaric hypoxia. Twenty-four, 7-wk-old Hubbard x Hubbard male chickens were lightly anesthetized and catheters were introduced into the right femoral artery and the pulmonary artery. The birds were then placed in a hypobaric chamber, and blood pressure responses were monitored during acute (15 min) exposures to simulated altitudes of 2,000 and 4,000 m. The pulmonary artery pressure increased . 7 and 4% during the first and second exposures to a simulated altitude of 2,000 m, whereas the femoral artery pressure decreased 6 and 8% during exposures to this altitude. The pulmonary artery pressure increased 7% on the first exposure and 23% (P < .05) on the second exposure to a simulated altitude of 4,000 m. The femoral arterial pressure decreased (P < .05) on both exposures to this altitude (29 and 24%, respectively). The initial femoral and pulmonary artery pressures and changes in these pressures upon exposure to hypobaric hypoxia were not consistently correlated with the characteristics of the electrocardiogram, packed cell volume, body weight, or the right:total ventricular weight ratio. These results indicate that acute hypobaric hypoxia elicits a hypotensive response in the systemic arterial circulation and a hypertensive response in the pulmonary arterial circulation of broiler chickens. (ABSTRACT TRUNCATED AT 250 WORDS)
Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload

Induction of the cell cycle is emerging as an intervention to treat heart failure. Here, we tested the hypothesis that enhanced cardiomyocyte renewal in transgenic mice expressing cyclin D2 would be beneficial during hemodynamic overload. We induced pressure overload by transthoracic aortic constriction (TAC) or volume overload by aortocaval shunt in cyclin D2–expressing and WT mice. Although cyclin D2 expression dramatically improved survival following TAC, it did not confer a survival advantage to mice following aortocaval shunt. Cardiac function decreased following TAC in WT mice, but was preserved in cyclin D2–expressing mice. On the other hand, cardiac structure and function were compromised in response to aortocaval shunt in both WT and cyclin D2–expressing mice. The preserved function and improved survival in cyclin D2–expressing mice after TAC was associated with an approximately 50% increase in cardiomyocyte number and exaggerated cardiac hypertrophy, as indicated by increased septum thickness. Aortocaval shunt did not further impact cardiomyocyte number in mice expressing cyclin D2. Following TAC, cyclin D2 expression attenuated cardiomyocyte hypertrophy, reduced cardiomyocyte apoptosis, fibrosis, calcium/calmodulin–dependent protein kinase II&dgr; phosphorylation, brain natriuretic peptide expression, and sustained capillarization. Thus, we show that cyclin D2–induced cardiomyocyte renewal reduced myocardial remodeling and dysfunction after pressure overload but not after volume overload.
Thyroid metabolism in the recessive sex-linked dwarf female chicken. 2. Binding of thyroid hormones by serum proteins.

Serum protein profiles were studied together with serum binding sites and capacity for L-thyroxine in dwarf and non-dwarf White Leghorn and White Rock breeds at ages 1 wk. , 4 wks. and in laying hens. Serum protein profiles varied with breed, strain and age. The percent gamma-globulin fraction was greater (P less than .05) in dwarf 1 wk. old and laying hens of the White Leghorn breed when compared with the normals. The only difference found in the White Rock breed was a decreased level of albumin in dwarf laying hens. There were no significant differences in the capacity or sites of binding of L-thyroxine to serum proteins although greater amounts of L-thyroxine were bound to globulin fractions in the dwarf. The data were interpreted to suggest that changes in serum protein profiles may have been the result of hypothyroidism at the cellular level but there was no reason to suspect abnormal binding of thyroid hormones to be the cause of that hypothyroidism.
Molecular orientation gradients in thermotropic liquid crystalline fiber

The degree of molecular alignment averaged over meso-length scale areas within thermotropic liquid crystalline polymer (LCP) fibers has been intensely studied over recent years. In this work, the degree of molecular orientation is found from spatially-resolved electron diffraction of areas as small as 100 nm in diameter to relieve structural averaging of lower resolution techniques. This investigation reveals that the maximum degree of molecular alignment across a fiber 18 μm in diameter is approximately 1 μm from the fiber surface. Dark-field imaging shows region with little crystallinity adjacent to the fiber surface. The banded structure, typical of TLCP fibers, is also less apparent in the surface region. Copyright © 2003 John Wiley & Sons, Ltd.
Dengue Therapeutics, Chemoprophylaxis, and Allied Tools: State of the Art and Future Directions

Dengue is the most common arboviral disease of humans. There is an unmet need for a therapeutic intervention that reduces the duration and severity of dengue symptoms and diminishes the likelihood of severe complications. To this end, there are active discovery efforts in industry and academia to develop interventions, with a focus on small molecule inhibitors of dengue virus replication that are suitable for therapy or chemoprophylaxis. Advancements in animal models of dengue virus infection together with the possibility of a dengue human infection model have further enhanced the platform for dengue drug discovery. Whilst drug discovery efforts gestate, there are ongoing clinical research designed to benefit today's patients, including trials of supportive care interventions, and descriptive studies that should improve the ability of clinicians to make an accurate diagnosis early in the illness course and to identify patients most at risk of progression to severe disease. This review provides a state of the art summary of dengue drug discovery, clinical trials, and supportive allied research and reflects discussions at the 2nd International Dengue Therapeutics Workshop held in Ho Chi Minh City, Vietnam, in December 2013.
Design of Two Alternative Routes for the Synthesis of Naftifine and Analogues as Potential Antifungal Agents

Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the γ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5–7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans.
Monitoring with Parametrized Extended Life Sequence Charts

Runtime verification is a lightweight verification technique that checks whether an execution of a system satisfies a given property. A problem in monitoring specification languages is to express parametric properties, where the correctness of a property depends on both the temporal relations of events, and the data carried by events. In this paper, we introduce parametrized extended live sequence charts (PeLSCs) for monitoring sequences of data-carrying events. The language of PeLSCs is extended from life sequence charts by introducing condition and assignment structures. We develop a translation from PeLSCs into the hybrid logic HL, and prove that the word problem of the PeLSCs is linear with respect to the size of a parametrized event trace. Therefore, the formalism is feasible for on-line monitoring.
The impact of ambrisentan and tadalafil upfront combination therapy on cardiac function in scleroderma associated pulmonary arterial hypertension patients: cardiac magnetic resonance feature tracking study

The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial-diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS-O trial (ambrisentan and tadalafil upfront combination therapy in SSc-PAH). Twenty-one patients completed the study protocol. Measures of RV systolic function (RV free wall [RVFW] peak longitudinal strain [pLS], RVFW peak longitudinal SRs [pLSRs]) and RV diastolic function (RVFW peak longitudinal SRa [pLSRa], RVFW peak circumferential SRe) were improved after treatment. LV systolic function (LV peak global longitudinal strain [pGLS]) and diastolic function (LV peak global longitudinal SRe [pGLSRe]) were also significantly improved at follow-up. Increased 6-min walk distance was significantly correlated with RVFW pLS and pLSRs, while the decrease in N-terminal pro-brain natriuretic peptide was correlated with LV pGLS. Increased cardiac index was associated with improved LV pGLSRe, and reduction in mean right atrial pressure was correlated with improved RVFW pLS and pLSRa. Combination therapy was associated with a significant improvement in both RV and LV function as assessed by CMR-derived strain and SR. Importantly, the improvement in RV and LV strain and SR correlated with improvements in known prognostic markers of PAH. (Approved by clinicaltrials.gov [NCT01042158] before patient recruitment.)
Fetal alcohol spectrum disorder and youth justice: a prevalence study among young people sentenced to detention in Western Australia

Objectives To estimate the prevalence of fetal alcohol spectrum disorder (FASD) among young people in youth detention in Australia. Neurodevelopmental impairments due to FASD can predispose young people to engagement with the law. Canadian studies identified FASD in 11%–23% of young people in corrective services, but there are no data for Australia. Design Multidisciplinary assessment of all young people aged 10–17 years 11 months and sentenced to detention in the only youth detention centre in Western Australia, from May 2015 to December 2016. FASD was diagnosed according to the Australian Guide to the Diagnosis of FASD. Participants 99 young people completed a full assessment (88% of those consented; 60% of the 166 approached to participate); 93% were male and 74% were Aboriginal. Findings 88 young people (89%) had at least one domain of severe neurodevelopmental impairment, and 36 were diagnosed with FASD, a prevalence of 36% (95% CI 27% to 46%). Conclusions This study, in a representative sample of young people in detention in Western Australia, has documented a high prevalence of FASD and severe neurodevelopmental impairment, the majority of which had not been previously identified. These findings highlight the vulnerability of young people, particularly Aboriginal youth, within the justice system and their significant need for improved diagnosis to identify their strengths and difficulties, and to guide and improve their rehabilitation.
Impact of bridging with perioperative low-molecular-weight heparin on cardiac and bleeding outcomes of stented patients undergoing non-cardiac surgery

Summary When patients with coronary stents undergo non-cardiac surgery, bridging therapy with low-molecular-weight heparin (LMWH) is not infrequent in clinical practice. However, the efficacy and safety of this approach is poorly understood. This was a retrospective analysis of patients with coronary stent(s) on any antiplatelet therapy undergoing non-cardiac surgery between March 2003 and February 2012. The primary efficacy endpoint was the 30-day incidence of major adverse cardiac or cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction, acute coronary syndrome leading to hospitalisation, or stroke. The primary safety endpoint was the 30-day composite of Bleeding Academic Research Consortium (BARC) bleedings ≥ 2. Among 515 patients qualifying for the analysis, LMWH bridging was used in 251 (49 %). At 30 days, MACCE occurred more frequently in patients who received LMWH (7.2 % vs 1.1 %, p=0.001), driven by a higher rate of myocardial infarction (4.8 % vs 0 %, p< 0.001). This finding was consistent across several instances of statistical adjustment and after the propensity matching of 179 pairs. Patients bridged with LMWH also experienced a significantly higher risk of BARC bleedings ≥ 2 (21.9 % vs 11.7 %, p=0.002) compared to those who were not, which remained significant across different methods of statistical adjustment and propensity matching. In conclusion, LMWH bridging in patients with coronary stents undergoing surgery is a common and possibly harmful practice, resulting in worse ischaemic outcomes at 30 days, and a significant risk of bleeding.