Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum Amyloid A3 Secreted by Preosteoclasts Inhibits Parathyroid Hormone-stimulated cAMP Signaling in Murine Osteoblasts*

Background: Continuous parathyroid hormone (PTH) is anabolic in cyclooxygenase-2 (Cox2) knock-out, but not WT, mice. Results: Preosteoclasts secreted serum amyloid A3 (Saa3) in response to RANKL only in the presence of Cox2. Saa3 blocked PTH-stimulated cAMP production and osteoblast differentiation. Conclusion: Saa3 is a novel means by which osteoclasts inhibit osteoblasts. Significance: Induction of Saa3 may explain why continuous PTH causes bone loss. Continuous parathyroid hormone (PTH) blocks its own osteogenic actions in marrow stromal cell cultures by inducing Cox2 and receptor activator of nuclear factor κB ligand (RANKL) in the osteoblastic lineage cells, which then cause the hematopoietic lineage cells to secrete an inhibitor of PTH-stimulated osteoblast differentiation. To identify this inhibitor, we used bone marrow macrophages (BMMs) and primary osteoblasts (POBs) from WT and Cox2 knock-out (KO) mice. Conditioned medium (CM) from RANKL-treated WT, but not KO, BMMs blocked PTH-stimulated cAMP production in POBs. Inhibition was reversed by pertussis toxin (PTX), which blocks Gαi/o activation. Saa3 was the most highly differentially expressed gene in a microarray comparison of RANKL-treated WT versus Cox2 KO BMMs, and RANKL induced Saa3 protein secretion only from WT BMMs. CM from RANKL-stimulated BMMs with Saa3 knockdown did not inhibit PTH-stimulated responses in POBs. SAA added to POBs inhibited PTH-stimulated cAMP responses, which was reversed by PTX. Selective agonists and antagonists of formyl peptide receptor 2 (Fpr2) suggested that Fpr2 mediated the inhibitory actions of Saa3 on osteoblasts. In BMMs committed to become osteoclasts by RANKL treatment, Saa3 expression peaked prior to appearance of multinucleated cells. Flow sorting of WT marrow revealed that Saa3 was secreted only from the RANKL-stimulated B220− CD3−CD11b−/low CD115+ preosteoclast population. We conclude that Saa3 secretion from preosteoclasts, induced by RANKL in a Cox2-dependent manner, inhibits PTH-stimulated cAMP signaling and osteoblast differentiation via Gαi/o signaling. The induction of Saa3 by PTH may explain the suppression of bone formation when PTH is applied continuously and may be a new therapeutic target for osteoporosis.
Superimposed Training Based Channel Estimation for OFDM Modulated Amplify-and-Forward Relay Networks

In this paper, we consider the channel estimation for the classical three-node relay networks that employ the amplify-and-forward (AF) transmission scheme and the orthogonal frequency division multiplexing (OFDM) modulation. We propose a superimposed training strategy that allows the destination node to separately obtain the channel information of the source→relay link and the relay→destination link. Specifically, the relay superimposes its own training signal over the received one before forwarding it to the destination. The proposed training strategy can be implemented within two transmission phases and is thus compatible with the two-phase data transmission scheme, i.e., the training can be embedded into data transmission. We also derive the Cramér-Rao bound for the random channel parameters, from which we compute the optimal training sequence as well as the optimal power allocation. Since the optimal minimum mean square error (MMSE) estimator and the maximum a posteriori (MAP) estimator cannot be expressed in closed-form, we propose to first obtain the initial channel estimates from the low complexity linear estimators, e.g., linear minimum mean-square error (LMMSE) and least square (LS) estimators, and then resort to the iterative method to improve the estimation accuracy. Simulation results are provided to corroborate the proposed studies.
KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese Type 2 diabetic patients

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with Type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA‐IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA‐IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.
Melt‐compounded butadiene rubber nanocomposites with improved mechanical properties and abrasion resistance

Hydrophobic polymers such as polyethylene and polypropylene are very difficult to use for preparing nanocomposites without a compatibilizer. However, in this study, polybutadiene rubber (BR; a hydrophobic polymer) nanocomposites were produced successfully without a compatibilizer with a melt-compounding method. Transmission electron microscopy showed an intercalated and exfoliated clay morphology in the polymer matrix, which led to increased mechanical properties. The tensile and tear strengths of the BR/Cloisite 20A hybrids were 4.4 times and 2 times larger than that of BR, respectively. The rebound resilience, compression set, and abrasion resistance were also improved by the addition of organoclay. The abrasion resistance of BR/Cloisite 20A was approximately 2 times larger than that of BR. The cure time (t90), scorch time (t2), and their difference (t90 − t2) of the BR/organoclay hybrids were much reduced than those of BR. Thus, organoclays behaved as good fillers and effective accelerant agents for BR vulcanization. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 2062–2066, 2006
Robust welding seam tracking using image seam extraction

Extracting single pixel wide paths is the core image processing problem in many vision based welding seam tracking applications. Traditional techniques such as edge detection and image thinning may not be effective for solving this problem on low quality welding images polluted by process noises. Based on the understanding of the prior knowledge about the welding images, we present in this paper a welding seam tracking method using the image seam extraction technique. Owing to its optimisation nature, the proposed method is robust to strong image noises caused by environmental factors such as uneven illumination, light interferences and welding spatters. In addition, the proposed method is of low time complexity and is highly adaptive to different types of welding images. Experimental results on a variety of welding images validate the effectiveness and efficiency of the proposed method.
Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for a Rat Organic Anion Transporting Polypeptide 1B2–Mediated Interaction in Hepatic Transport

Cytochrome P450 enzymes and human organic anion transporting polypeptide (OATP) 1B1 are reported to be involved in the pharmacokinetics of lobeglitazone (LB), a new peroxisome proliferator–activated receptor γ agonist. Atorvastatin (ATV), a substrate for CYP3A and human OATP1B1, is likely to be coadministered with LB in patients with the metabolic syndrome. We report herein on a study of potential interactions between LB and ATV in rats. When LB was administered intravenously with ATV, the systemic clearance and volume of distribution at steady state for LB remained unchanged (2.67 ± 0.63 ml/min per kg and 289 ± 20 ml/kg, respectively), compared with that of LB without ATV (2.34 ± 0.37 ml/min per kg and 271 ± 20 ml/kg, respectively). Although the tissue-to-plasma partition coefficient (Kp) of LB was not affected by ATV in most major tissues, the liver Kp for LB was decreased by ATV coadministration. Steady-state liver Kp values for three levels of LB were significantly decreased as a result of ATV coadministration. LB uptake was inhibited by ATV in rat OATP1B2-overexpressing Madin–Darby canine kidney cells and in isolated rat hepatocytes in vitro. After incorporating the kinetic parameters for the in vitro studies into a physiologically based pharmacokinetics model, the characteristics of LB distribution to the liver were consistent with the findings of the in vivo study. It thus appears that the distribution of LB to the liver is mediated by the hepatic uptake of transporters such as rat OATP1B2, and carrier-mediated transport is involved in the liver-specific drug–drug interaction between LB and ATV in vivo.
Air-writing recognition using reverse time ordered stroke context

A novel real-time recognition system is proposed to recognize finger air-writing characters without using any pen-starting-lift information. It presents a novel reverse time ordered stroke context to represent an air-writing trajectory in a backward way so that redundant starting-lift data can be effectively filtered out. Another two challenging problems often happen in the air-writing recognition system, i.e., the multiplicity problem of writing and the confusion problem. The first one means a character is always written differently and the second one means different various characters own similar writing trajectory. To tackle them, a three-layer hierarchical structure to represent an air-writing character with different sampling rates is proposed. All the alphabets (including lowercase, capital, and digital letters) are recognized in this system. Performance evaluation shows that the proposed solution achieves quite higher recognition accuracy (more than 94.7%) even though no starting gesture is required.
A Memory-Based Lemmatizer for Ancient Greek

In this paper we present the lemmatizer that we developed for Ancient Greek: GLEM. As far as we know, GLEM is the first publicly available lemmatizer for Ancient Greek that uses POS information to disambiguate and that also assigns output to unseen words, words that are not yet in the lexicon. As the basis for the lemmatizer we used an existing memory-based learning tool, Frog, that was originally developed for Dutch and that we converted to work for Ancient Greek. As the results of Frog on Ancient Greek were rather modest, we used Frog to create a smarter lemmatizer, GLEM, that uses a lexicon look up in addition to the memory-based tool Frog. We evaluate and compare the performance of GLEM against the Frog lemmatizer and the already existing CLTK lemmatizer and observe that GLEM achieves the highest accuracy of 93% on an unseen test corpus sample. GLEM's look up component overcomes the difficulty of a relative small training set in combination with a morphologically rich language, while the memory-based learning component enables GLEM to handle unknown words.
The LysR-Type Transcriptional Regulator QseD Alters Type Three Secretion in Enterohemorrhagic Escherichia coli and Motility in K-12 Escherichia coli

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 responds to the host-produced epinephrine and norepinephrine, and bacterially produced autoinducer 3 (AI-3), through two-component systems. Further integration of multiple regulatory signaling networks, involving regulators such as the LysR-type transcriptional regulator (LTTR) QseA, promotes effective regulation of virulence factors. These include the production of flagella, a phage-encoded Shiga toxin, and genes within the locus of enterocyte effacement (LEE) responsible for attaching and effacing (AE) lesion formation. Here, we describe a new member of this signaling cascade, an LTTR heretofore renamed QseD (quorum-sensing E. coli regulator D). QseD is present in all enterobacteria but exists almost exclusively in O157:H7 isolates as a helix-turn-helix (HTH) truncated isoform. This “short” isoform (sQseD) is still able to regulate gene expression through a different mechanism than the full-length K-12 E. coli “long” QseD isoform (lQseD). The EHEC ΔqseD mutant exhibits increased expression of all LEE operons and deregulation of AE lesion formation. The loss of qseD in EHEC does not affect motility, but the K-12 ΔqseD mutant is hypermotile. While the lQseD directly binds to the ler promoter, encoding the LEE master regulator, to repress LEE transcription, the sQseD isoform does not. LTTRs bind to DNA as tetramers, and these data suggest that sQseD regulates ler by forming heterotetramers with another LTTR. The LTTRs known to regulate LEE transcription, QseA and LrhA, do not interact with sQseD, suggesting that sQseD acts as a dominant-negative partner with a yet-unidentified LTTR.
Short-time traffic flow prediction with ARIMA-GARCH model

Short-time traffic flow prediction is a significant interest in transportation study, and it is essential in congestion control and traffic network management. In this paper, we propose an Autoregressive Integrated Moving Average with Generalized Autoregressive Conditional Heteroscedasticity (ARIMA-GARCH) model for traffic flow prediction. The model combines linear ARIMA model with nonlinear GARCH model, so it can capture both the conditional mean and conditional heteroscedasticity of traffic flow series. The model is calibrated, validated and used for prediction based on PeMS single loop detector data. The performance of the hybrid model is compared with that of standard ARIMA model. The results show that the introduction of conditional heteroscedasticity cannot bring satisfactory improvement to prediction accuracy, in some cases the general GARCH(1,1) model may even deteriorate the performance. Thus for ordinary traffic flow prediction, the standard ARIMA model is sufficient.
In-bed patient motion and pose analysis using depth videos for pressure ulcer prevention

We present a real-time depth based computer vision system for pressure ulcer prevention, in-bed patient care and monitoring. Our system can effectively determine whether or not a mobility-compromised patient has been correctly repo-sitioned at the required frequency. A depth sensor is used to detect and recognize patient movements, motion patterns, and pose positions. If the patient has stayed in an unchanged pose for too long and needs pressure releasing movements, our system can notify caregivers for repositioning or assistance. Privacy concerns are mitigated by removing the RGB components of the video stream from the camera capturing, and only processing depth measurements. We collaborated with clinical practitioners at the Charlie Norwood VA Medical Center for in-field data collection and experimental evaluation. A web portal front-end is developed such that all historical patient movements, pose positions, and repositioning data can be organized to support telehealth applications.
Late Ca2+ Sparks and Ripples During the Systolic Ca2+ Transient in Heart Muscle Cells

Rationale: The development of a refractory period for Ca2+ spark initiation after Ca2+ release in cardiac myocytes should inhibit further Ca2+ release during the action potential plateau. However, Ca2+ release sites that did not initially activate or which have prematurely recovered from refractoriness might release Ca2+ later during the action potential and alter the cell-wide Ca2+ transient. Objective: To investigate the possibility of late Ca2+ spark (LCS) activity in intact isolated cardiac myocytes using fast confocal line scanning with improved confocality and signal to noise. Methods and Results: We recorded Ca2+ transients from cardiac ventricular myocytes isolated from rabbit hearts. Action potentials were produced by electric stimulation, and rapid solution changes were used to modify the L-type Ca2+ current. After the upstroke of the Ca2+ transient, LCSs were detected which had increased amplitude compared with diastolic Ca2+ sparks. LCS are triggered by both L-type Ca2+ channel activity during the action potential plateau, as well as by the increase of cytosolic Ca2+ associated with the Ca2+ transient itself. Importantly, a mismatch between sarcoplasmic reticulum load and L-type Ca2+ trigger can increase the number of LCS. The likelihood of triggering an LCS also depends on recovery from refractoriness that appears after prior activation. Consequences of LCS include a reduced rate of decline of the Ca2+ transient and, if frequent, formation of microscopic propagating Ca2+ release events (Ca2+ ripples). Ca2+ ripples resemble Ca2+ waves in terms of local propagation velocity but spread for only a short distance because of limited regeneration. Conclusions: These new types of Ca2+ signaling behavior extend our understanding of Ca2+-mediated signaling. LCS may provide an arrhythmogenic substrate by slowing the Ca2+ transient decline, as well as by amplifying maintained Ca2+ current effects on intracellular Ca2+ and consequently Na+/Ca2+ exchange current.
Effect of apoptosis‐associated speck‐like protein containing a caspase recruitment domain on vaccine efficacy: Overcoming the effects of its deficiency with aluminum hydroxide adjuvant

Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine‐induced humoral and cell‐mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC) is one of the main components of inflammasomes, but it is not clear whether ASC affects the vaccine‐induced immune response. Herein, we used two types of vaccines: inactivated influenza vaccine not formulated with alum, and HPV vaccine formulated with alum. We gave the vaccines to ASC knockout (ASC−/−) mice to investigate the role of ASC in vaccine efficacy. Influenza vaccine‐immunized ASC−/− mice did not show antibody titers in week 2 after the first vaccination. After boosting, the antibody titer in ASC−/− mice was about half that in wild type (WT) mice. Furthermore, a cytotoxic T‐lymphocyte response against influenza vaccine was not induced in ASC−/− mice. Therefore, vaccinated ASC−/− mice did not show effective protection against viral challenge. ASC−/− mice immunized with alum‐formulated HPV vaccine showed similar antibody titers and T‐cell proliferation compared with immunized WT mice. However, the HPV vaccine without alum induced up to threefold lower titers of HPV‐specific antibody titers in ASC−/− mice compared with those in WT mice. These findings suggest that alum in vaccine can overcome the ASC‐deficient condition.
Nutrition to Support Recovery from Endurance Exercise: Optimal Carbohydrate and Protein Replacement

Proper nutrition is vital to optimize recovery after endurance exercise. Dietary carbohydrate and protein provide the requisite substrates to enhance glycogen resynthesis and remodel skeletal muscle proteins, respectively, both of which would be important to rapidly restore muscle function and performance. With short recovery windows (<8 h), coingestion of these macronutrients immediately after exercise can synergistically enhance glycogen resynthesis and rapidly stimulate muscle protein synthesis (MPS), the latter of which is augmented by protein ingestion alone. Consuming frequent meals throughout the day containing adequate carbohydrate (according to training intensity) and protein (approximately 0.25 g·kg−1) will help fully restore muscle glycogen and sustain maximal daily rates of MPS over prolonged (8 to 24 h) recovery periods. Given the complementarity of these macronutrients, endurance athletes aiming to maximize postexercise recovery to maintain or enhance subsequent exercise performance should target a nutrition strategy that features optimal ingestion of both carbohydrate and protein.
Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B Cell Maturation and Mitogen-Stimulated Proliferation

Apoptosis is critical to B cell maturation, but studies of apoptotic regulation in primary human B cells is lacking. In this study, we sought to better understand the mechanisms of apoptotic regulation in normal and activated B cells. Using intracellular BH3 profiling, we defined the Bcl2 dependency of B cell subsets from human peripheral blood and tonsillar lymphoid tissue as well as mitogen-activated B cells. We found that naive and memory B cells were BCL-2–dependent, whereas germinal center B cells were MCL-1–dependent and plasma cells were BCL-XL–dependent. B cells stimulated to proliferate ex vivo by CpG or CD40L/IL-4 became more dependent on MCL-1 and BCL-XL. As B cell lymphomas often rely on survival mechanisms derived from normal and activated B cells, these findings offer new insight into potential therapeutic strategies for lymphomas.
Image‐based models of cardiac structure in health and disease

Computational approaches to investigating the electromechanics of healthy and diseased hearts are becoming essential for the comprehensive understanding of cardiac function. In this article, we first present a brief review of existing image‐based computational models of cardiac structure. We then provide a detailed explanation of a processing pipeline which we have recently developed for constructing realistic computational models of the heart from high resolution structural and diffusion tensor (DT) magnetic resonance (MR) images acquired ex vivo. The presentation of the pipeline incorporates a review of the methodologies that can be used to reconstruct models of cardiac structure. In this pipeline, the structural image is segmented to reconstruct the ventricles, normal myocardium, and infarct. A finite element mesh is generated from the segmented structural image, and fiber orientations are assigned to the elements based on DTMR data. The methods were applied to construct seven different models of healthy and diseased hearts. These models contain millions of elements, with spatial resolutions in the order of hundreds of microns, providing unprecedented detail in the representation of cardiac structure for simulation studies. Copyright © 2010 John Wiley & Sons, Inc.