Miracle-dz/UniFAR-FTUs huggingface dataset:
Mammalian Polynucleotide Phosphorylase Is an Intermembrane Space RNase That Maintains Mitochondrial Homeostasis

ABSTRACT We recently identified polynucleotide phosphorylase (PNPase) as a potential binding partner for the TCL1 oncoprotein. Mammalian PNPase exhibits exoribonuclease and poly(A) polymerase activities, and PNPase overexpression inhibits cell growth, induces apoptosis, and stimulates proinflammatory cytokine production. A physiologic connection for these anticancer effects and overexpression is difficult to reconcile with the presumed mitochondrial matrix localization for endogenous PNPase, prompting this study. Here we show that basal and interferon-β-induced PNPase was efficiently imported into energized mitochondria with coupled processing of the N-terminal targeting sequence. Once imported, PNPase localized to the intermembrane space (IMS) as a peripheral membrane protein in a multimeric complex. Apoptotic stimuli caused PNPase mobilization following cytochrome c release, which supported an IMS localization and provided a potential route for interactions with cytosolic TCL1. Consistent with its IMS localization, PNPase knockdown with RNA interference did not affect mitochondrial RNA levels. However, PNPase reduction impaired mitochondrial electrochemical membrane potential, decreased respiratory chain activity, and was correlated with altered mitochondrial morphology. This resulted in FoF1-ATP synthase instability, impaired ATP generation, lactate accumulation, and AMP kinase phosphorylation with reduced cell proliferation. Combined, the data demonstrate an unexpected IMS localization and a key role for PNPase in maintaining mitochondrial homeostasis.
Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase‐1 and phosphatase‐2A with peptides

Protein phosphatase‐1 and phosphatase‐2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past. In the last decade, new approaches have been developed to overcome these hurdles and have strongly revived the field. I will focus here on peptide‐based approaches, which contributed to showing that these phosphatases can be targeted selectively and aided in rethinking the design of selective phosphatase modulators. Finally, I will give a perspective on www.depod. org, the human dephosphorylation database, and how it can aid phosphatase modulator design. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.
Avaliação das respostas psicofisíologicas associadas à memória emocional em um teste auditivo-visual

The memory enhancement phenomenon is the process by which information related to emotional content is more easily remembered and remains available to recalling for more time than information not related to emotional content. The objective of this work was to study the relationship between arousal, subjective scores for basic emotions, sex of the participants and autonomic activity during encoding and recalling of the information, using an audio-visual test of emotional memory. The results demonstrated that the emotional content of the information induced higher level of Arousal, Surprise, Fear, Angry and Sadness, and was better remembered than the information without emotional content. Men and women recognized self-reference information better than information without such characteristic. Correlations between emotional and recognition scores demonstrated that Arousal level was associated to Surprise feelings and negative-valenced emotions. Declarative memory for emotional content was positive correlated to Surprise and Sadness in women, and negatively to Angry in men. The emotional content induced a differentiated physiological activity (pulse frequency and skin conductance) during encoding and recalling phases, suggesting a correlation of autonomic activity with the memory enhancing phenomenon. During the recalling session men and women showed different autonomic responses. These results support the hypothesis of a differentiated processing of emotional information between men and women, as well as interactions between arousal and emotional valence, demonstrating their importance in the study of the mechanisms of emotional memory and in the design of future experiments.
A Novel Method for Modeling RFID Data

The applications of Radio Frequency Identification (RFID) and Electronic Product Code (EPC) in supply chain management have vast potential in improving effectiveness and efficiencies in solving supply chain problems. RFID data, however, have their own unique characteristics – including aggregation, location, temporal and history-oriented – which have to be fully considered and integrated into the RFID data model which is constructed for RFID application system. In this paper, we use an expressive temporal data model for RFID data. This data model is based on Entity-Relation (ER) model with minimum extension and highlights the state history and temporal semantics of the RFID system business processes. We also show common RFID data tracking and monitoring types, and propose methods to express such queries based on this data model.
EDAN: EMG-controlled Daily Assistant

Neuromuscular diseases, stroke, or trauma can lead to a reduced neural function which severely inhibits limb functionality. If the disease is strongly advanced, people can’t manage their daily life independently and become reliant on 24-hour care. In this situation, assistive technology, like a robotic manipulator mounted on a wheelchair, can provide help and relief. However, control of such a device is usually achieved with a joystick, which requires to have remaining functionality in hand and finger movement. This prevents many people with tetraplegia from efficient use of such assistive technology. An alternative to the joystick, is given by Brain-Computer Interfaces. It has been shown that noninvasive interfaces like Electroencephalography can be used to achieve control over low-dimensional devices like power wheelchairs [3]. More complex tasks like control of assistive robotic devices have been demonstrated with invasive interfaces, like the BrainGate Neural Interface System [1]. We investigate the use of surface Electromyography (EMG) as an interface for assistive robotic devices. It is a comparably cheap and easy to apply technology. We could show that people with tetraplegia due to a severe Spinal Muscular Atrophy (SMA), can still achieve control over a robotic manipulator (e.g. drinking from a bottle) by recording remaining muscular activity [4]. To investigate the use of EMG as an interface to assistive technology, we developed the research platform EDAN (EMG-controlled Daily Assistant). It consists of a robotic manipulator mounted on a state of the art power wheelchair. We use a torque controlled robotic arm (DLR-LWR 3), which is well suited for safe physical interaction with humans and the environment. The five-finger hand mounted on the robotic arm allows for stable grasping of a variety of everydayobjects. The focus of our research is twofold. On the one hand, we investigate the use of EMG as a non-invasive interface to provide people with control over assistive systems. On the other hand, we develop methods to simplify the usage of such systems with the support of artificial intelligence. Manual control of robotic manipulators is rather slow and cumbersome, especially when controlled with a noisy interface like a BCI. Artificial intelligence can help to significantly improve the usability of such systems. A shared control ap-
Adaptation strategies to seasonal changes in environmental conditions of a domesticated horse breed, the Shetland pony (Equus ferus caballus)

SUMMARY Recent results suggest that the wild ancestor of the horse, the Przewalski horse, exhibits signs of a hypometabolism. However, there are speculations that domestic animals lost the ability to reduce energy expenditure during food shortage and adverse environmental conditions. Therefore, we investigated physiological and behavioural strategies employed by a robust domesticated horse breed, the Shetland pony, over the course of a year under temperate conditions by measuring ambient temperature (Ta), subcutaneous temperature (Ts), locomotor activity (LA), lying time, resting heart rate, body mass and body condition score. Ten animals were kept on pasture in summer and in open stables in winter; further, in winter the animals were allocated into one control and one feed-restricted group of five animals each to simulate natural seasonal food shortage. The annual course of the mean daily Ts of all horses showed distinct fluctuations from a mean of 35.6±0.5°C, with higher variations in summer than in winter. Diurnal amplitudes in Ts were highest (P<0.001) in April (12.6°C) and lowest in January (4.0°C), with a nadir around dawn and a peak around mid-day. The feed-restricted group had a significantly lower daily Ts compared with the control group on cold winter days, with Ta values below 0°C. Mean annual heart rate and LA followed Ta closely. Heart rate of the feed-restricted animals significantly decreased from a mean of 52.8±8.1 beats min–1 in summer to 29±3.9 beats min–1 in winter and differed from the control group (P<0.001). Mean daily LA was lowest at the end of winter (7000 activity impulses day–1) and highest in summer (25,000 activity impulses day–1). Our results show that Shetland ponies exhibit signs of a winter hypometabolism indicated by reduced heart rate and Ts. Thus, domesticated horses seem to have maintained the capacity for seasonal adaptation to environmental conditions by seasonal fluctuations in their metabolic rate.
Adjuvants targeting innate and adaptive immunity synergize to enhance tumor immunotherapy

Because of mechanisms of self-tolerance, many tumor-specific CD8 T cells exhibit low avidity for tumor antigens and would benefit from strategies that enhance their numbers and effector function. Here we demonstrate that the combined use of two different types of immune adjuvants, one that directly targets the CD8 cell, IL-2/anti-IL-2 mAb complexes, and one that targets the innate immune system, poly(I:C), can achieve this goal. Provision of IL-2/mAb complexes was found to enhance the activation and effector function of low-avidity tumor-specific T cells, yet this was insufficient to achieve tumor eradication. The addition of poly(I:C) further increased the accumulation of granzyme B-expressing effectors within the tumor and resulted in tumor eradication. This strategy presents many of the benefits of whole-body irradiation, including the provision of high levels of homeostatic cytokines, enhanced expansion of effector cells relative to regulatory T cells, and provision of inflammatory cytokines, and is therefore likely to serve as a strategy for both tumor vaccines and adoptive immunotherapy of cancer.
Crisis in intercountry adoption, crisis in adoptive families

Based on a key note address given at the European Society on Family Relations conference in Madrid 2014, this article gives a general overview of some specific challenges adoptive families and adoption researchers face in recent years. Three crises in the area of adoption research are outlined: (1) the steady decline in the number of international adoptions; (2) the difficulties adoptees and their families face when the adoptee reaches adolescence; and (3) the problems associated with defining and investigating adoption breakdowns and the outcomes for these adoptees. While each of these issues pose a significant threat to the well-being of adoptees, fortunately the majority adoptees benefit from finding an adoptive family.
Securing building management systems using named data networking

Recently, building automation and management systems, BASs and BMSs, have shifted from using proprietary protocols and specialized hardware toward widespread adoption of IP-based open standard technologies. While the IP protocol suite improves software and hardware interoperability, practical large-scale BMS deployments face challenges, including the complexity of network addressing and other configuration, reliance on middleware for even relatively simple tasks, and a lack of security. In this article, we propose a data-centric BMS design that uses named data networking, one of the proposed information-centric networking architecture designs. Our sensor data acquisition system uses a hierarchical namespace for data, encryption keys, and access control lists, implements encryption-based access control, and provides a web browser-based data visualization interface that communicates in NDN. Our design has been deployed on a UCLA campus testbed that captures, archives, and visualizes data from industry standard sensors.
Pattern-based Aggregation of Named Entity Extractors

Despite significant advances in named entity extraction technologies, state-of-the-art extraction tools achieve insufficient accuracy rates for practical use in many operational settings. However, they are not all prone to the same types of error, suggesting that substantial improvements may be achieved via appropriate combinations of existing tools, provided their behavior can be accurately characterized and quantified. In this paper, we present an inference framework that leverages the joint characteristics of their error processes via a pattern-based representation of extracted entity data. This approach has been shown to produce statistically significant improvements in entity extraction relative to standard performance metrics and to mitigate the weak performance of entity extractors operating under suboptimal conditions. Moreover, this aggregation methodology provides a framework for quantifying uncertainty in extracted entity output, and it can readily adapt to sparse data conditions.
Predicting the Performance of Parsing with Referential Translation Machines

Abstract Referential translation machine (RTM) is a prediction engine used for predicting the performance of natural language processing tasks including parsing, machine translation, and semantic similarity pioneering language, task, and domain independence. RTM results for predicting the performance of parsing (PPP) in out-of-domain or in-domain settings with different training sets and types of features present results independent of language or parser. RTM PPP models can be used without parsing using only text input and without any parser or language dependent information. Our results detail prediction performance, top selected features, and lower bound on the prediction error of PPP.
Functional, Biophysical, and Structural Bases for Antibacterial Activity of Tigecycline

ABSTRACT Tigecycline is a novel glycylcycline antibiotic that possesses broad-spectrum activity against many clinically relevant species of bacterial pathogens. The mechanism of action of tigecycline was delineated using functional, biophysical, and molecular modeling experiments in this study. Functional assays showed that tigecycline specifically inhibits bacterial protein synthesis with potency 3- and 20-fold greater than that of minocycline and tetracycline, respectively. Biophysical analyses demonstrated that isolated ribosomes bind tigecycline, minocycline, and tetracycline with dissociation constant values of 10−8, 10−7, and >10−6 M, respectively. A molecular model of tigecycline bound to the ribosome was generated with the aid of a 3.40-angstrom resolution X-ray diffraction structure of the 30S ribosomal subunit from Thermus thermophilus. This model places tigecycline in the A site of the 30S subunit and involves substantial interactions with residues of H34 of the ribosomal subunit. These interactions were not observed in a model of tetracycline binding. Modeling data were consistent with the biochemical and biophysical data generated in this and other recent studies and suggested that tigecycline binds to bacterial ribosomes in a novel way that allows it to overcome tetracycline resistance due to ribosomal protection.
Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud.

Bone morphogenetic proteins (BMPs) constitute a large family of secreted signals involved in the formation of the skeleton but the specific function of each member of this family remains elusive. GDF-5 is a member of the BMP family which has been implicated in several skeletogenic events including the induction and growth of the appendicular cartilages, the determination of joint forming regions, and the establishment of tendons. Here, we have studied the function of GDF-5 in digit skeletogenesis by analyzing the effects of its local administration in the developing autopod of embryonic chick and the regulation of its pattern of gene expression by other signals involved in digit morphogenesis. As reported in the mouse, the gdf-5 gene exhibits a precise distribution in the joint-forming regions of the developing chicken digital rays. GDF-5 beads implanted at the tip of the digits promote intense cartilage growth and fail to induce morphological or molecular signs of joint formation. Furthermore, GDF-5 beads implanted in the interdigits inhibit the formation of joints in the adjacent digits. These data suggest that the role of GDF-5 in joint formation is the control of growth and differentiation of the cartilage of the epiphyseal regions of the phalanges rather than accounting for the differentiation of the sinovial joint tissues. The interdigital mesoderm in spite of its potential to form ectopic digits with their tendinous apparatus failed to form either ectopic cartilages or ectopic tendons after the implantation of GDF-5 beads in the stages preceding cell death. At difference with other BMPs, GDF-5 exhibited only a weak cell death promoting effect. The BMP antagonist Noggin binds to GDF-5 and is able to inhibit all the observed effects of this growth factor in vivo. Potential interactions of GDF-5 with other signals involved in digits morphogenesis were also explored. BMP-7 regulates negatively the expression of gdf-5 gene in the joint forming regions and local treatment with Noggin induces the ectopic expression of gdf-5 in the interdigital mesoderm. Retroviral-induced misexpression of Indian or Sonic Hedgehog genes in the developing digits leads to the formation of digits without joints in which gdf-5 expression occurs throughout the entire perichondrial surface. In conclusion, this study indicates that GDF-5 is a signal regulated by other BMPs which controls the growth and differentiation of the epiphyses of the digital cartilages acting in close relationship with Hedgehog signaling.
The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis*

Objective:In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal N&ohgr;-nitro-l-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Design:Prospective crossover and randomized control interventional studies. Setting:University-affiliated research institute. Subjects:Thirty-two merino ewes. Intervention:Examination of responses to intrarenal infusion of N&ohgr;-nitro-l-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. Measurements and Main Results:In normal sheep, N&ohgr;-nitro-l-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of N&ohgr;-nitro-l-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of N&ohgr;-nitro-l-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. Conclusions:In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal N&ohgr;-nitro-l-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney injury is not the result of decreased renal blood flow nor is it improved by nonspecific nitric oxide synthase inhibition.
Quality of life and diabetes

Quality of life is an important health outcome in its own right, representing the ultimate goal of all health interventions. This paper reviews the published, English‐language literature on self‐perceived quality of life among adults with diabetes. Quality of life is measured as physical and social functioning, and perceived physical and mental well‐being. People with diabetes have a worse quality of life than people with no chronic illness, but a better quality of life than people with most other serious chronic diseases. Duration and type of diabetes are not consistently associated with quality of life. Intensive treatment does not impair quality of life, and having better glycemic control is associated with better quality of life. Complications of diabetes are the most important disease‐specific determinant of quality of life. Numerous demographic and psychosocial factors influence quality of life and should be controlled when comparing subgroups. Studies of clinical and educational interventions suggest that improving patients' health status and perceived ability to control their disease results in improved quality of life. Methodologically, it is important to use multidimensional assessments of quality of life, and to include both generic and disease‐specific measures. Quality of life measures should be used to guide and evaluate treatment interventions. Copyright © 1999 John Wiley & Sons, Ltd.
Differential Association and Delinquency

An important task of research in the field of juvenile delinquency, and indeed in sociology and science generally, is the testing of theories set forth in the literature but not previously subjected to empirical inquiry. The social sciences contain many such theories, based on case studies, historical examples, or the synthesis of other theoretical and empirical work. Some of these become virtually sacrosanct through continued usage, particularly in textbook form, though they remain untested in any systematic way.