Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR‐137 inhibited inflammatory response and apoptosis after spinal cord injury via targeting of MK2

Spinal cord injuries are common and troublesome disorder, which is mediated by various signal pathways and mechanisms. MK2 is also involved in numerous inflammatory diseases including spinal cord injury. The role of microRNA‐137 (miR‐137) and its detailed working mechanism in spinal cord injuries remain unclear. In the present study, we found that an elevated MK2 but a decreased miR‐137 was expressed in serum specimens of patients with spinal cord injury and in hydrogen peroxide‐treated C8‐D1A and C8‐B4 cells. Meanwhile, we suggested that upregulation of miR‐137 could inhibit the expression of TNF‐α and IL‐6, two markers of inflammatory response after SCI, and apoptosis in hydrogen peroxide‐treated C8‐D1A and C8‐B4 cells. Furthermore, we verified that MK2 was a direct target of miR‐137 thorough a constructed luciferase assay. Even further, we elucidated that miR‐137 could suppress the inflammatory response and apoptosis via negative regulation of MK2. Finally, through an animal model trial performed using mice, we demonstrated the protective effect of how miR‐137 works on inflammatory response and apoptosis after spinal cord injury. Considering all the forementioned, our findings revealed that miR‐137 inhibited inflammatory response and apoptosis after spinal cord injury via the targeting of MK2. The outcomes of the present study might indicate a new target in molecular treatment of SCI.
DJ-1 promotes development of DEN-induced hepatocellular carcinoma and proliferation of liver cancer cells

Chronic liver inflammation and injuries play a critical role in development of hepatocellular carcinoma (HCC). Parkinson disease (autosomal recessive, early onset) 7, encoding PARK7 protein (also called DJ-1), plays important roles in many carcinogenesis processes and is essential in modulating inflammation. However, whether DJ-1 is involved in HCC development remains largely unknown. To determine the effect of DJ-1 on HCC development, we accessed the correlation of hepatic DJ-1 expression with overall survival (OS) and TNM stage in 96 HCC patients and found a significant inverse correlation between DJ-1 expression and OS. By adopting a classic diethylnitrosamine (DEN)-induced murine HCC model, DJ-1 knockout (KO) mice displayed reduced tumorigenesis and cell proliferation, accompanied by decreased hepatic inflammation and IL-6/STAT3 activation. Furthermore, after an acute DEN challenge, DJ-1 KO mice showed significant decreases in liver injury, hepatocyte proliferation and DNA damage. In a human HCC cell line (MHCC-97L), cancer cell proliferation was induced by overexpression of DJ-1 and is related to oncogenic signaling of MAPKs and AKT. Induction of DJ-1 may serve as a novel regulator for HCC cell proliferation and HCC development possibly through enhanced MAPK signaling and inflammation.
The Effects of Immigration on NHS Waiting Times

This paper analyzes the effects of immigration on waiting times for the National Health Service (NHS) in England. Linking administrative records from Hospital Episode Statistics (2003-2012) with immigration data drawn from the UK Labour Force Survey, we find that immigration reduced waiting times for outpatient referrals and did not have significant effects on waiting times in accident and emergency departments (A&E) and elective care. The reduction in outpatient waiting times can be explained by the fact that immigration increases natives' internal mobility and that immigrants tend to be healthier than natives who move to different areas. Finally, we find evidence that immigration increased waiting times for outpatient referrals in more deprived areas outside of London. The increase in average waiting times in more deprived areas is concentrated in the years immediately following the 2004 EU enlargement and disappears in the medium term (e.g., 3-4 years).
Rifabutin Is Active against Mycobacterium abscessus Complex

ABSTRACT Lung infections caused by Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation. M. abscessus is an intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of M. abscessus lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an M. abscessus clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three M. abscessus subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii CCUG 50184-T, and M. abscessus subsp. massiliense CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the Mycobacterium abscessus complex bacteria in vitro and may be considered for treatment of M. abscessus lung disease.
Soft Robotics with Compliance and Adaptation for Biomedical Applications and forthcoming Challenges

Biology has always motivated engineers to come up with efficient and reliable machines to move in complex environments. The dexterity, softness, and body compliance of natural system such as cephalopods or caterpillars have inspired robotic engineers to incorporate soft, deformable materials such as gels and elastomers into their designs. Hence, the inception of soft robots shifts the paradigm and trends in robotics, which could potentially revolutionize health care, human– robot interaction, field exploration, rehabilitation, and related applications. Throughout this review article, we have restricted our discussion to the applications of soft robots in biomedical domains exclusively and the perennial challenges faced therein.
Convergence of the Iterative Methods for Coordinate- Splitting Formulation in Multibody Dynamics.

Abstract : In a previous paper, we introduced a coordinate-splitting (CS) form of the equations of motion for multibody systems which together with a modified nonlinear iteration (CM), is particularly effective in the solution of certain nonlinear highly oscillatory systems. In this paper, we examine the convergence of the CS and CM iterations and explain the improved convergence of the CM iteration. An example is given from flexible body simulation which illustrates the convergence results and the class of problems for which the CM iteration is most effective.
High-Dimensional Vector Semantics

In this paper we explore the “vector semantics” problem from the perspective of “almost orthogonal” property of high-dimensional random vectors. We show that this intriguing property can be used to “memorize” random vectors by simply adding them, and we provide an efficient probabilistic solution to the set membership problem. Also, we discuss several applications to word context vector embeddings, document sentences similarity, and spam filtering.
Novel Semantics-based Distributed Representations for Message Polarity Classification using Deep Convolutional Neural Networks

: Unsupervised learning of distributed representations (word embeddings) obviates the need for task-speciﬁc feature engineering for various NLP applications. However, such representations learned from massive text datasets do not faithfully represent ﬁner semantic information in the feature space required by speciﬁc applications. This is owing to the fact that (a) models learning such representations ignore the linguistic structure of the sentences, (b) they fail to capture polysemous usages of the words, and (c) they ignore pre-existing semantic information from manually-created ontologies. In this paper, we propose three semantics-based distributed representations of words and phrases as features for message polarity classiﬁcation: Sentiment-Speciﬁc Multi-Word Expressions Embeddings(SSMWE) are sentiment encoded distributed representations of multi-word expressions (MWEs) ; Sense-Disambiguated Word Embeddings(SDWE) are sense-speciﬁc distributed representations of words; and WordNet embeddings(WNE) are distributed representations of hypernym and hyponym of the correct sense of a given word. We examine the effects of these features incorporated in a convolutional neural network(CNN) model for evaluation on the SemEval benchmarked dataset. Our approach of using these novel features yields 14.24% improvement in the macro-averaged F1 score on SemEval datasets over existing methods. While we have shown promising results in twitter sentiment classiﬁcation, we believe that the method is general enough to be applied to many NLP applications where ﬁner semantic analysis is required.
Managing Animal Sounds - Some Challenges and Research Directions

For decades, biologists around the world have recorded animal sounds. As the number of records grows, so does the difﬁculty to manage them, presenting challenges to save, retrieve, share and manage the sounds. This paper presents our preliminary results concerning management of large volumes of animal sound data. The paper also provides an overview from our prototype, an online environment focused on management of this data. This paper also discusses our case study, concerning more than 1 terabyte of animal recordings from Fonoteca Neotropical ”Jacques Vielliard”, at UNICAMP, Brazil.
Optimal Design and Operation of a Gas-to-liquid Process

In this study we used a commercial process simulator to model a gas to liquid (GTL) plant and evaluated different process alternatives from an economical point of view. These alternatives include different syngas unit configurations and the effect of removing CO2 from the tail gas. The criteria used to compare different syngas configurations is payout time. Results show that the most economically attractive syngas technology for GTL applications is an ATR. A case study is conducted to investigate the effect of removing CO2 from the tail gas. Results show that the carbon efficiency for an optimized ATR-based process with and without CO2 removal unit is 77.3 % and 73.5 %, respectively.
Experimental investigation of accommodation in eyes fit with multifocal contact lenses using a clinical auto‐refractor

Multifocal or multi‐zone contact lenses are increasingly being fit to young eyes in an attempt to control myopia progression. However, success in achieving this aim may depend on how much the eye accommodates. The purpose of the current work was to evaluate the ability of an open‐field clinical autorefractor to measure on‐axis refractive state and accommodation in eyes fit with multifocal contact lenses (CLs).
A New CMOS Active Transformer QPSK Modulator With Optimal Bandwidth Control

This brief presents a new quadrature phase-shift keying (QPSK) modulator for Bluetooth applications with an optimal transaction bandwidth control. The modulator reduces the bandwidth of the modulated carrier by minimizing their transition sharpness. CMOS active transformers are developed and utilized in quadrature oscillator and multiplexer of the modulator to provide comparable phase noise performance without using spiral inductors and transformers. The performance of the modulator is assessed using a 1.6-GHz QPSK base-band modulator implemented in TSMC 0.18-mum 1.8-V CMOS technology and analyzed using SpectreRF from Cadence Design Systems with BSIM3v3 device models. The total transistor area and power consumption of the modulator are 2840 mum2 and 30 mW, respectively. The phase noise of the quadrature oscillator is 110 dBc/Hz at 500-kHz frequency offset.
Ergosterol is mainly located in the cytoplasmic leaflet of the yeast plasma membrane

Transbilayer lipid asymmetry is a fundamental characteristic of the eukaryotic cell plasma membrane (PM). While PM phospholipid asymmetry is well documented, the transbilayer distribution of PM sterols such as mammalian cholesterol and yeast ergosterol is not reliably known. We now report that sterols are asymmetrically distributed across the yeast PM, with the majority (~80%) located in the cytoplasmic leaflet. By exploiting the sterol‐auxotrophic hem1Δ yeast strain we obtained cells in which endogenous ergosterol was quantitatively replaced with dehydroergosterol (DHE), a closely related fluorescent sterol that functionally and accurately substitutes for ergosterol in vivo. Using fluorescence spectrophotometry and microscopy we found that <20% of DHE fluorescence was quenched when the DHE‐containing cells were exposed to membrane‐impermeant collisional quenchers (spin‐labeled phosphatidylcholine and trinitrobenzene sulfonic acid). Efficient quenching was seen only after the cells were disrupted by glass‐bead lysis or repeated freeze‐thaw to allow quenchers access to the cell interior. The extent of quenching was unaffected by treatments that deplete cellular ATP levels, collapse the PM electrochemical gradient or affect the actin cytoskeleton. However, alterations in PM phospholipid asymmetry in cells lacking phospholipid flippases resulted in a more symmetric transbilayer distribution of sterol. Similarly, an increase in the quenchable pool of DHE was observed when PM sphingolipid levels were reduced by treating cells with myriocin. We deduce that sterols comprise up to ~45% of all inner leaflet lipids in the PM, a result that necessitates revision of current models of the architecture of the PM lipid bilayer.
Joint longitudinal hurdle and time‐to‐event models: an application related to viral load and duration of the first treatment regimen in patients with HIV initiating therapy

Shared parameter joint models provide a framework under which a longitudinal response and a time to event can be modelled simultaneously. A common assumption in shared parameter joint models has been to assume that the longitudinal response is normally distributed. In this paper, we instead propose a joint model that incorporates a two‐part ‘hurdle’ model for the longitudinal response, motivated in part by longitudinal response data that is subject to a detection limit. The first part of the hurdle model estimates the probability that the longitudinal response is observed above the detection limit, whilst the second part of the hurdle model estimates the mean of the response conditional on having exceeded the detection limit. The time‐to‐event outcome is modelled using a parametric proportional hazards model, assuming a Weibull baseline hazard. We propose a novel association structure whereby the current hazard of the event is assumed to be associated with the current combined (expected) outcome from the two parts of the hurdle model. We estimate our joint model under a Bayesian framework and provide code for fitting the model using the Bayesian software Stan. We use our model to estimate the association between HIV RNA viral load, which is subject to a lower detection limit, and the hazard of stopping or modifying treatment in patients with HIV initiating antiretroviral therapy. Copyright © 2016 John Wiley & Sons, Ltd.
Combined Dietary Anthocyanins, Flavonols, and Stilbenoids Alleviate Inflammatory Bowel Disease Symptoms in Mice

Dietary polyphenols are associated with a wide range of health benefits, protecting against chronic diseases and promoting healthy aging. Dietary polyphenols offer a complementary approach to the treatment of inflammatory bowel diseases (IBDs), a group of common chronic intestinal inflammation syndromes for which there is no cure. Tomato is widely consumed but its content of polyphenols is low. We developed a tomato variety, Bronze, enriched in three distinct classes of polyphenols: flavonols, anthocyanins, and stilbenoids. Using Bronze tomatoes as a dietary supplement as well as Indigo (high anthocyanins and flavonols), ResTom (high stilbenoids) and wild-type tomatoes, we examined the effects of the different polyphenols on the host gut microbiota, inflammatory responses, and the symptoms of chronic IBD, in a mouse model. Bronze tomatoes significantly impacted the symptoms of IBD. A similar result was observed using diets supplemented with red grape skin containing flavonols, anthocyanins, and stilbenoids, suggesting that effective protection is provided by different classes of polyphenols acting synergistically.
Human Induced Pluripotent Stem Cell–Derived Motor Neuron Transplant for Neuromuscular Atrophy in a Mouse Model of Sciatic Nerve Injury

Importance Human motor neurons may be reliably derived from induced pluripotent stem cells (iPSCs). In vivo transplant studies of human iPSCs and their cellular derivatives are essential to gauging their clinical utility. Objective To determine whether human iPSC-derived motor neurons can engraft in an immunodeficient mouse model of sciatic nerve injury. Design, Setting, and Subjects This nonblinded interventional study with negative controls was performed at a biomedical research institute using an immunodeficient, transgenic mouse model. Induced pluripotent stem cell–derived motor neurons were cultured and differentiated. Cells were transplanted into 32 immunodeficient mice with sciatic nerve injury aged 6 to 15 weeks. Tissue analysis was performed at predetermined points after the mice were killed humanely. Animal experiments were performed from February 24, 2015, to May 2, 2016, and data were analyzed from April 7, 2015, to May 27, 2016. Interventions Human iPSCs were used to derive motor neurons in vitro before transplant. Main Outcomes and Measures Evidence of engraftment based on immunohistochemical analysis (primary outcome measure); evidence of neurite outgrowth and neuromuscular junction formation (secondary outcome measure); therapeutic effect based on wet muscle mass preservation and/or electrophysiological evidence of nerve and muscle function (exploratory end point). Results In 13 of the 32 mice undergoing the experiment, human iPSC-derived motor neurons successfully engrafted and extended neurites to target denervated muscle. Human iPSC-derived motor neurons reduced denervation-induced muscular atrophy (mean [SD] muscle mass preservation, 54.2% [4.0%]) compared with negative controls (mean [SD] muscle mass preservation, 33.4% [2.3%]) (P = .04). No electrophysiological evidence of muscle recovery was found. Conclusions and Relevance Human iPSC-derived motor neurons may have future use in the treatment of peripheral motor nerve injury, including facial paralysis. Level of Evidence NA.
Obtaining copper with harmonic structure for the optimal balance of structure-performance relationship

Materials having bimodal grain structures are known for the good balance of strength and ductility. However, methods for their fabrication often lack the control of such structure characteristics. In this work, the principles of "harmonic" structure fabrication allowing to control both topology and scale of the bimodal structure heterogeneity have been concisely formulated. The feasibility to form the "harmonic structure" in pure copper has been demonstrated, and the advantages of tensile performance of the material with such a structure is analyzed.
Practice Prize Winner - Pricing Digital Content Product Lines: A Model and Application for the National Academies Press

We examine the problem of how a content provider, specifically the National Academies Press (NAP), can optimally price the different forms of its product---print and PDF---that it sells online. Whereas products in the traditional product line generally tend to be substitutes, the different content product forms could range from being substitutes to being complements across customers. Thus the content provider can possibly sell bundles of the product forms, leading to additional revenue. We first discuss NAP's decision context and describe the model we proposed for developing NAP's optimal pricing policies for its different forms. We describe the choice experiment we conducted on the publisher's website that maximally uses the online interface to collect relevant data needed to estimate our model. We show how NAP embraced the results from the model for developing a new business model and how it used the insights derived from the study to set pricing policies and monitor sales performance as a function of pricing. Finally, we perform validation of the model and the implemented policies using dynamic modeling of sales data from NAP's website. The paper illustrates how e-commerce technologies can lead to the development of optimal policies using marketing models.
Pyridostigmine Improves the Effects of Resistance Exercise Training after Myocardial Infarction in Rats

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Exercise training and pharmacological treatments are important strategies to minimize the deleterious effects of MI. However, little is known about the effects of resistance training combined with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on the inflammatory profile after MI. Thus, in the present study, male Wistar rats were randomly assigned into: control (Cont); sedentary infarcted (Inf); PYR – treated sedentary infarcted rats (Inf+P); infarcted rats undergoing resistance exercise training (Inf+RT); and infarcted rats undergoing PYR treatment plus resistance training (Inf+RT+P). After 12 weeks of resistance training (15–20 climbs per session, with a 1-min rest between each climb, at a low to moderate intensity, 5 days a week) and/or PYR treatment (0.14 mg/mL of drink water), hemodynamic function, autonomic modulation, and cytokine expressions were evaluated. We observed that 3 months of PYR treatment, either alone or in combination with exercise, can improve the deleterious effects of MI on left ventricle dimensions and function, baroreflex sensitivity, and autonomic parameters, as well as systemic and tissue inflammatory profile. Furthermore, additional benefits in a maximal load test and anti-inflammatory state of skeletal muscle were found when resistance training was combined with PYR treatment. Thus, our findings suggest that the combination of resistance training and PYR may be a good therapeutic strategy since they promote additional benefits on skeletal muscle anti-inflammatory profile after MI.