Miracle-dz/UniFAR-FTUs huggingface dataset:
Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins

Human serum paraoxonase is located on an HDL. It has the capacity to retard the accumulation of lipid peroxides in LDL under oxidizing conditions in vitro. Paraoxonase has a genetic polymorphism that results in a single amino acid substitution. Evidence indicates that both the serum concentration of paraoxonase and an individual's genotype are related to plasma lipid and lipoprotein concentrations, and possibly also to coronary heart disease, implicating paraoxonase in the development of atherosclerosis.
Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer

ABSTRACT Purpose: Drugs that blockade interaction between programmed cell-death protein 1 (PD-1) and its ligand (PD-L1) are promising. Immune-related adverse events (irAEs) might be associated with favorable clinical outcomes, and thyroid dysfunction is one of the most common irAE. We evaluated the association of thyroid dysfunction during PD-1 blockade with the treatment efficacy in patients with non-small cell lung cancer (NSCLC). Experimental Design: A total 58 patients with stage IV NSCLC treated with PD-1 blockade were enrolled. Patients were categorized into thyroid dysfunction and euthyroid groups. Overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Patients, tumor, and medication factors were adjusted using Cox proportional hazard modeling. Objective response rate (RR) and durable control rate were assessed according to the severity of thyroid dysfunction. Results: OS [median 118.0 (73.0-267.0) vs. 71.0 (28.0-160.0) days, log-rank P = 0.025] and PFS [118.0 (73.0-267.0) vs. 61.0 (28.0-130.0), log-rank P = 0.014] were longer in the thyroid dysfunction group. After adjustment, thyroid dysfunction was an independent predictive factor for favorable outcome [adjusted HR = 0.11 (95% CI) 0.01-0.92 for overall death; 0.38 (0.17-0.85) for disease progression]. The severity of thyroid dysfunction was associated with durable control rate (P for trend = 0.008). Conclusions: Thyroid dysfunction during PD-1 blockade is associated with treatment response and could provide supplementary information for immune monitoring in patients with advanced NSCLC.
Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders.
CANSE: A Churn Adaptive Approach to Network Size Estimation

Network size is one of the fundamental information of distributed applications. The approach to estimate network size must feature both high accuracy and robustness in order to adapt to the dynamic environment in different topologies. However, existing approaches fail to guarantee accuracy and robustness simultaneously in dynamic topologies due to the randomness of nodes sampled. In this paper, we propose a churn adaptive approach to network size estimation – CANSE, which collects closest nodes in identification to each node’s identification by sampling nodes periodically. Each node collects closest identifications by two schemes. One scheme is sampling random nodes from random walks along the topology. The other one is exchanging the closest identifications with other nodes. Finally, each node calculates the average spacing of the closest identifications collected to estimate network size. Compared with existing approaches, extensive experiments show that CANSE provides accurate estimation values quickly in various dynamic topologies.
Spanish EuroWordNet and LCS-based interlingual MT

We present a machine translation framework in which the interlingua— Lexical Conceptual Structure (LCS)—is coupled with a definitional component that includes bilingual (EuroWordNet) links between words in the source and target languages. While the links between individual words are language-specific, the LCS is designed to be a language-independent, compositional representation. We take the view that the two types of information—shallower, transfer-like knowledge as well as deeper, compositional knowledge—can be reconciled in interlingual machine translation, the former for overcoming the intractability of LCS-based lexical selec- tion, and the latter for relating the underlying semantics of two words cross-linguistically. We describe the acquisition process for these two information types and present results of hand-verification of the acquired lexicon. Finally, we demonstrate the utility of the two information types in interlingual MT.
The human Müller cell line MIO-M1 expresses opsins

Purpose To determine whether the human Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1) expresses opsins. Methods The gene expression of opsins was determined by reverse-transcription PCR (RT–PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. Results MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red-green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. Conclusions The human Müller cell line MIO-M1 expresses opsins. This suggests immortalized Müller cells could be used as a cellular source to produce human opsins for their potential application as therapeutic agents in patients with retinitis pigmentosa.
AS CONNECTORS IN COMPONENT-BASED DEVELOPMENT

Several proposals for component-based development methods have started to appear. However, the emphasis is still very much on the development of components as opposed to the development with components. The main focus is on how to generate ideal reusable components not on how to plug existing components and specify their interactions and connections. The concept of a coordination contract (Andrade and Fiadeiro 1999; Andrade and Fiadeiro 2001; Andrade, Fiadeiro et al. 2001) has been proposed to specify a mechanism of interaction between objects based on the separation between structure, what is stable, and interaction, what is changeable. This separation supports better any change of requirements, as contracts can be replaced, added or removed dynamically, i.e. in run-time, without having to interfere with the components that they coordinate. A coordination contract corresponds to an expressive architectural connector that can be used to plug existing components. In this paper we integrate the concept of a coordination contract with component-based development and show how coordination contracts can be used to specify the connectors between components.
Continuous Detour Queries in Spatial Networks

We study the problem of finding the shortest route between two locations that includes a stopover of a given type. An example scenario of this problem is given as follows: “On the way to Bob's place, Alice searches for a nearby take-away Italian restaurant to buy a pizza. ” Assuming that Alice is interested in minimizing the total trip distance, this scenario can be modeled as a query where the current Alice's location (start) and Bob's place (destination) function as query points. Based on these two query points, we find the minimum detour object (MDO), i.e., a stopover that minimizes the sum of the distances: 1) from the start to the stopover, and 2) from the stopover to the destination. In a realistic location-based application environment, a user can be indecisive about committing to a particular detour option. The user may wish to browse multiple (k) MDOs before making a decision. Furthermore, when a user moves, the kMDO results at one location may become obsolete. We propose a method for continuous detour query (CDQ) processing based on incremental construction of a shortest path tree. We conducted experimental studies to compare the performance of our proposed method against two methods derived from existing k-nearest neighbor querying techniques using real road-network data sets. Experimental results show that our proposed method significantly outperforms the two competitive techniques.
Moyamoya disease

Moyamoya disease is a disorder of blood vessels in the brain, specifically the internal carotid arteries and the arteries that branch from them. These vessels, which provide oxygen-rich blood to the brain, narrow over time. Narrowing of these vessels reduces blood flow in the brain. In an attempt to compensate, new networks of small, fragile blood vessels form. These networks, visualized by a particular test called an angiogram, resemble puffs of smoke, which is how the condition got its name: "moyamoya" is an expression meaning "something hazy like a puff of smoke" in Japanese.
Real-World Lessons From the Implementation of a Depression Screening Protocol in Acute Myocardial Infarction Patients: Implications for the American Heart Association Depression Screening Advisory

Background— The American Heart Association (AHA) statement has recommended routine screening for depression in coronary artery disease with a 2-stage implementation of the Patient Health Questionnaire (PHQ). Because there is little evidence on feasibility, accuracy, and impact of such a program on depression recognition in coronary patients, the AHA recommendation has met substantial debate and criticism. Methods and Results— Before the AHA statement was released, the Mid America Heart and Vascular Institute (MAHVI) had implemented a depression screening protocol for patients with acute myocardial infarction that was virtually identical to the AHA recommendations. To (1) evaluate this MAHVI quality improvement initiative, (2) compare MAHVI depression recognition rates with those of other hospitals, and (3) examine health care providers' implementation feedback, we compared the results of the MAHVI screening program with data from a parallel prospective acute myocardial infarction registry and interviewed MAHVI providers. Depressive symptoms (PHQ-2, PHQ-9) were assessed among 503 MAHVI acute myocardial infarction patients and compared with concurrent depression assessments among 3533 patients at 23 US centers without a screening protocol. A qualitative summary of providers' suggestions for improvement was also generated. A total of 135 (26.8%) eligible MAHVI patients did not get screened. Among screened patients, 90.9% depressed (PHQ-9 ≥10) patients were recognized. The agreement between the screening and registry data using the full PHQ-9 was 61.5% for positive cases (PHQ-9 ≥10) but only 35.6% for the PHQ-2 alone. Although MAHVI had a slightly higher overall depression recognition rate (38.3%) than other centers not using a depression screening protocol (31.5%), the difference was not statistically significant (P=0.31). Staff feedback suggested that a single-stage screening protocol with continuous feedback could improve compliance. Conclusions— In this early effort to implement a depression screening protocol, a large proportion of patients did not get screened, and only a modest impact on depression recognition rates was realized. Simplifying the protocol by using the PHQ-9 alone and providing more support and feedback may improve the rates of depression detection and treatment.
Investigation of back-off based interpolation between recurrent neural network and n-gram language models

Recurrent neural network language models (RNNLMs) have become an increasingly popular choice for speech and language processing tasks including automatic speech recognition (ASR). As the generalization patterns of RNNLMs and n-gram LMs are inherently different, RNNLMs are usually combined with n-gram LMs via a fixed weighting based linear interpolation in state-of-the-art ASR systems. However, previous work doesn't fully exploit the difference of modelling power of the RNNLMs and n-gram LMs as n-gram level changes. In order to fully exploit the detailed n-gram level complementary attributes between the two LMs, a back-off based compact representation of n-gram dependent interpolation weights is proposed in this paper. This approach allows weight parameters to be robustly estimated on limited data. Experimental results are reported on the three tasks with varying amounts of training data. Small and consistent improvements in both perplexity and WER were obtained using the proposed interpolation approach over the baseline fixed weighting based linear interpolation.
A Comparison of Continuous and Distributed Reduced Sleep Schedules

After a night of normal sleep, 36 subjects were divided into three groups of 12. One group was allowed to continue sleeping normally, one group had four hours continuous sleep and the third group had three 80-min periods of sleep distributed throughout the 24-h period, for the next four days. Subjects were given a visual vigilance test on each day. Overall performance was rather better following distributed than following continuous reduced sleep, but rather worse than following 8 h of sleep. The main difference between the reduced sleep groups was in their decision criterion. It was suggested that this difference mainly reflected the difference in time since the two groups had last slept.
Membrane self‐assembly processes: Steps toward the first cellular life

This review addresses the question of the origin of life, with emphasis on plausible boundary structures that may have initially provided cellular compartmentation. Some form of compartmentation is a necessary prerequisite for maintaining the integrity of interdependent molecular systems that are associated with metabolism, and for permitting variations required for speciation. The fact that lipid‐bilayer membranes define boundaries of all contemporary living cells suggests that protocellular compartments were likely to have required similar, self‐assembled boundaries. Amphiphiles such as short‐chain fatty acids, which were presumably available on the early Earth, can self‐assemble into stable vesicles that encapsulate hydrophilic solutes with catalytic activity. Their suspensions in aqueous media have therefore been used to investigate nutrient uptake across simple membranes and encapsulated catalyzed reactions, both of which would be essential processes in protocellular life forms. Anat Rec 268:196–207, 2002. © 2002 Wiley‐Liss, Inc.
Highly compact 3.1 -10.6 GHz UWB LNA in SiGe HBT technology

We present the design, implementation and measurement of a low noise amplifier (LNA) in a low cost 0.8 mum SiGe heterojunction bipolar technology (HBT). The measured noise figure is between 2.1 dB and 2.6 dB in the FCC-allocated bandwidth for ultra-wideband (UWB) systems. The circuit delivers 19.6 dB peak gain with gain variations of 1.3 dB within the entire band from 3.1 to 10.6 GHz. Broadband noise and power matching has been achieved with a cascode topology using resistive shunt feedback in combination with a diode DC level shifter. The measured input IP3 is -14.1 dBm with 10.3 mA total current from a 3.5 V supply. AH performance characteristics are comparable to the best reported UWB LNAs but come at a drastically smaller occupied die area of 0.13 mm2.
Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play essential roles in the maintenance of energy balance and glucose metabolism. The data discussed indicate that dietary PUFA function as fuel partitioners in that they direct glucose toward glycogen storage, and direct fatty acids away from triglyceride synthesis and assimilation and toward fatty acid oxidation. In addition, the n-3 family of PUFA appear to have the unique ability to enhance thermogenesis and thereby reduce the efficiency of body fat deposition. PUFA exert their effects on lipid metabolism and thermogenesis by up-regulating the transcription of the mitochondrial uncoupling protein-3, and inducing genes encoding proteins involved in fatty acid oxidation (e.g. carnitine palmitoyltransferase and acyl-CoA oxidase) while simultaneously down-regulating the transcription of genes encoding proteins involved in lipid synthesis (e.g. fatty acid synthase). The potential transcriptional mechanism and the transcription factors affected by PUFA are discussed. Moreover, the data are interpreted in the context of the role that PUFA may play as dietary factors in the development of obesity and insulin resistance. Collectively the results of these studies suggest that the metabolic functions governed by PUFA should be considered as part of the criteria utilized in defining the dietary needs for n-6 and n-3 PUFA, and in establishing the optimum dietary ratio for n-6 : n-3 fatty acids.
Collective Goods, Common Agency, and Third-Party Intervention

Voluntary contributions to multiple public goods may involve many contributors (principals) who condition their payments to a single provider (agent) based on realized provision. If the agent's efforts on these goods are unobservable, then a common agency problem results with a third-best outcome owing to agency costs, free riding, and competitive interests. The latter manifests itself in the principals punishing the agent for providing an alternative public good (for which they have no interest) to a different set of principals. Remedies may require multiple policy instruments unlike the standard prescription for the public good or common agency problem in isolation. Moreover, the sequence of actions is essential for addressing the combined problems.
China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses

Purpose of review China has experienced an increase in the incidence and prevalence of syphilis that is especially remarkable since this infection was virtually eradicated in the country 50 years ago. The purpose of this analysis is to provide an overview of recent literature on syphilis proximate determinants and potential public health responses. Recent findings Per capita syphilis burden is greatest in coastal urban China. There are a number of biological, demographic, geographic, and behavioral/social proximate determinants of syphilis spread that distinguish the Chinese syphilis epidemic. These determinants portend the need for intensified syphilis control efforts, including: comprehensive testing and treatment; integration with HIV, sexually transmitted infection, and antenatal services; scale-up of novel rapid syphilis test technology, and multisectorial support. Summary The Chinese central government recently announced a 10-year syphilis plan to provide clear expectations for evaluating the success of local syphilis control programs and integration with HIV testing programs. Further research is needed to understand the social and behavioral determinants driving the spread of syphilis.
Phosphodiesterase Type 3A Regulates Basal Myocardial Contractility Through Interacting With Sarcoplasmic Reticulum Calcium ATPase Type 2a Signaling Complexes in Mouse Heart

Rationale: cAMP is an important regulator of myocardial function, and regulation of cAMP hydrolysis by cyclic nucleotide phosphodiesterases (PDEs) is a critical determinant of the amplitude, duration, and compartmentation of cAMP-mediated signaling. The role of different PDE isozymes, particularly PDE3A vs PDE3B, in the regulation of heart function remains unclear. Objective: To determine the relative contribution of PDE3A vs PDE3B isozymes in the regulation of heart function and to dissect the molecular basis for this regulation. Methods and Results: Compared with wild-type littermates, cardiac contractility and relaxation were enhanced in isolated hearts from PDE3A−/−, but not PDE3B−/−, mice. Furthermore, PDE3 inhibition had no effect on PDE3A−/− hearts but increased contractility in wild-type (as expected) and PDE3B−/− hearts to levels indistinguishable from PDE3A−/−. The enhanced contractility in PDE3A−/− hearts was associated with cAMP-dependent elevations in Ca2+ transient amplitudes and increased sarcoplasmic reticulum (SR) Ca2+ content, without changes in L-type Ca2+ currents of cardiomyocytes, as well as with increased SR Ca2+-ATPase type 2a activity, SR Ca2+ uptake rates, and phospholamban phosphorylation in SR fractions. Consistent with these observations, PDE3 activity was reduced ≈8-fold in SR fractions from PDE3A−/− hearts. Coimmunoprecipitation experiments further revealed that PDE3A associates with both SR calcium ATPase type 2a and phospholamban in a complex that also contains A-kinase anchoring protein-18, protein kinase type A-RII, and protein phosphatase type 2A. Conclusions: Our data support the conclusion that PDE3A is the primary PDE3 isozyme modulating basal contractility and SR Ca2+ content by regulating cAMP in microdomains containing macromolecular complexes of SR calcium ATPase type 2a–phospholamban–PDE3A.