Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal Muscle DNA Damage Precedes Spinal Motor Neuron DNA Damage in a Mouse Model of Spinal Muscular Atrophy (SMA)

Spinal Muscular Atrophy (SMA) is a hereditary childhood disease that causes paralysis by progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN) protein, due to mutations in the Survival of Motor Neuron 1 gene. The mechanisms by which lack of SMN causes SMA pathology are not known, making it very difficult to develop effective therapies. We investigated whether DNA damage is a perinatal pathological event in SMA, and whether DNA damage and cell death first occur in skeletal muscle or spinal cord of SMA mice. We used a mouse model of severe SMA to ascertain the extent of cell death and DNA damage throughout the body of prenatal and newborn mice. SMA mice at birth (postnatal day 0) exhibited internucleosomal fragmentation in genomic DNA from hindlimb skeletal muscle, but not in genomic DNA from spinal cord. SMA mice at postnatal day 5, compared with littermate controls, exhibited increased apoptotic cell death profiles in skeletal muscle, by hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, and electron microscopy. SMA mice had no increased cell death, no loss of choline acetyl transferase (ChAT)-positive motor neurons, and no overt pathology in the ventral horn of the spinal cord. At embryonic days 13 and 15.5, SMA mice did not exhibit statistically significant increases in cell death profiles in spinal cord or skeletal muscle. Motor neuron numbers in the ventral horn, as identified by ChAT immunoreactivity, were comparable in SMA mice and control littermates at embryonic day 15.5 and postnatal day 5. These observations demonstrate that in SMA, disease in skeletal muscle emerges before pathology in spinal cord, including loss of motor neurons. Overall, this work identifies DNA damage and cell death in skeletal muscle as therapeutic targets for SMA.
Fibroblast growth factor‐2 converts PACAP growth action on embryonic hindbrain precursors from stimulation to inhibition

Pituitary adenylyl cyclase activating peptide (PACAP) has been shown either to stimulate or to inhibit neural cell proliferation depending on the origin of the cell population. We show here that, depending on the presence or absence of fibroblast growth factor‐2 (FGF‐2, also called basic FGF), PACAP may either stimulate or inhibit DNA synthesis in neural precursors isolated from embryonic day 10.5 mouse hindbrain. In the absence of FGF‐2, PACAP stimulated 3H‐thymidine incorporation in a dose‐dependent manner. This stimulatory action was unaffected by antagonists of protein kinases A and C but was abolished in the presence of the MEK1/2 antagonist PD98059. In contrast, when FGF‐2 was present, PACAP inhibited DNA synthesis. This inhibitory action was insensitive to PD98059 but was fully blocked by the protein kinase A (PKA) inhibitor H89. The differential blockades by MEK1/2 and PKA inhibitors indicate that the FGF‐2‐induced switch in PACAP action on DNA synthesis was accomplished by a change in PACAP signaling pathways. We hypothesize that the actions of PACAP in the specific parts of the developing nervous system are determined in part by the presence or absence of FGFs and other growth factors. © 2002 Wiley‐Liss, Inc.
IP Modularity: Profiting from Innovation by Aligning Product Architecture with Intellectual Property

Firms seeking to take advantage of distributed innovation and outsourcing can bridge the tension between value creation and value capture by modifying the modular structure of their technical systems. Specifically, this article introduces the concept of “IP modularity,” which seeks to protect and capture value from intellectual property. The article defines what it means for a system to be “IP-modular,” illustrates the application of this concept in a number of practical situations, and presents a comprehensive framework that can be used to design and evaluate value capture strategies for modular systems.
Improving performance of loops on DIAM-based VLIW architectures

Recent studies show that very long instruction word (VLIW) architectures, which inherently have wide datapath (e.g. 128 or 256 bits for one VLIW instruction word), can benefit from dynamic implied addressing mode (DIAM) and can achieve lower power consumption and smaller code size with a small performance overhead. Such overhead, which is claimed to be small, is mainly caused by the execution of additionally generated special instructions for conveying information that cannot be encoded in reduced instruction bit-width. In this paper, however, we show that the performance impact of applying DIAM on VLIW architecture cannot be overlooked expecially when applications possess high level of instruction level parallelism (ILP), which is mostly the case for loops because of the result of aggressive code scheduling. We also propose a way to relieve the performance degradation especially focusing on loops since loops spend almost 90% of total execution time in programs and tend to have high ILP. We first implement the original DIAM compilation technique in a compiler, and augment it with the proposed loop optimization scheme to show that ours can clearly alleviate the performance loss caused by the excessive number of additional instructions, with the help of slightly modified hardware. Moreover, the well-known loop unrolling scheme, which would produce denser code in loops at the cost of substantial code size bloating, is integrated into our compiler. The experiment result shows that the loop unrolling technique, combined with our augmented DIAM scheme, produces far better code in terms of performance with quite an acceptable amount of code increase.
Learning Continuous Action Models in a Real-Time Strategy Environment

Although several researchers have integrated methods for reinforcement learning (RL) with case-based reasoning (CBR) to model continuous action spaces, existing integrations typically employ discrete approximations of these models. This limits the set of actions that can be modeled, and may lead to non-optimal solutions. We introduce the Continuous Action and State Space Learner (CASSL), an integrated RL/CBR algorithm that uses continuous models directly. Our empirical study shows that CASSL significantly outperforms two baseline approaches for selecting actions on a task from a real-time strategy gaming environment.
Murine Models of Acute Leukemia: Important Tools in Current Pediatric Leukemia Research

Leukemia remains the most common diagnosis in pediatric oncology and, despite dramatic progress in upfront therapy, is also the most common cause of cancer-related death in children. Much of the initial improvement in outcomes for acute lymphoblastic leukemia (ALL) was due to identification of cytotoxic agents that are active against leukemia followed by the recognition that combination of these cytotoxic agents and prolonged therapy are essential for cure. Recent data demonstrating lack of progress in patients for whom standard chemotherapy fails suggests that the ability to improve outcome for these children will not be dramatically impacted through more intensive or newer cytotoxic agents. Thus, much of the recent research focus has been in the area of improving our understanding of the genetics and the biology of leukemia. Although in vitro studies remain critical, given the complexity of a living system and the increasing recognition of the contribution of leukemia extrinsic factors such as the bone marrow microenvironment, in vivo models have provided important insights. The murine systems that are used can be broadly categorized into syngeneic models in which a murine leukemia can be studied in immunologically intact hosts and xenograft models where human leukemias are studied in highly immunocompromised murine hosts. Both of these systems have limitations such that neither can be used exclusively to study all aspects of leukemia biology and therapeutics for humans. This review will describe the various ALL model systems that have been developed as well as discuss the advantages and disadvantages inherent to these systems that make each particularly suitable for specific types of studies.
Estilos de Aprendizagem e Estratégias de Ensino em Engenharia Química

Studies in educational psychology show that factors such as personality, life history, culture, motiva tion, and environmental factors modify the perception that th e subject has of reality, influencing the learning processes. The act of learning is a complex activity that needs to be understood in its dimensions: individual and so cial. Learning is both the motivation and interest of the subject who learns how the quality of mediation between the learner and the object of knowledge. In this sense, the investi gative study of the different learning styles (Feld er and Silverman, 1988) of students of Chemical Engineering at UFV and its socioeconomic and cultural profile is relevant and necessary to the definition of teachin g strategies that best suit the characteristics of these students. Knowing the preferred styles of students, teachers may propose appropriate interventions aimed at impr oving learning and contemplate all students. It is conclu ded that it is possible to define teaching strategi es based in the students' learning styles to improve the teaching-l earning process in the Chemical Engineering.
A MICROMETHOD FOR DETERMINATION OF BRADYKININOGEN UNDER SEVERAL CONDITIONS *

The study of the bradykinin precursor-bradykininogen(BKG)in plasma or other biological fluids is of obvious importance in understanding the role of this polypeptide in several physiological and pathological conditions. The determination of the BKG variations under various circumstances might give an insight in the extent of the mobilization of the biochemical process responsible for the release of bradykinin in blood. Bradykinin itself is difficult to assay in blood because i t is on one hand quickly destroyed by the powerful bradykininolytic enzymes present in this fluid and on the other hand i t is diluted in the extracellular fluids of the animal body. From a biochemical point of view it is also of interest to understand the metabolic alterations of such a specific protein as BKG under a variety of experimental and clinical conditions. As a first step, a simplified method for BKG determination was developed in this laboratory. ' The method and its use in the study of some experimental and clinical problems will be reviewed in this paper.
A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma.

BACKGROUND The purpose of our cooperative trial was to investigate whether epirubicin (EPI) at 90 mg/m2 in a CHOP-like combination (called CEOP) could increase complete response (CR) and survival rates in non-Hodgkin lymphoma (NHL) patients while maintaining a tolerable degree of toxicity. METHODS Between September 1986 and July 1992, 218 patients from 12 Centers in Lombardy entered this study. The inclusion criteria were: a histological diagnosis of intermediate or diffuse large cell (DLC) NHL and no previous radio-chemotherapy. The patients in stages IA and IIA (both intermediate and DLC) received four CEOP courses followed by local/regional radiotherapy; those with intermediate NHL in stages IB, IIB, III A and B and IV A and B received six CEOP courses and, if they achieved CR, three further courses as consolidation. RESULTS Among the 160 evaluable patients, CR was observed in 90% of the subjects with DLC-NHL (stages IA and IIA) and in 59% of those with intermediate-grade NHL (all clinical stages). If the clinical stages are considered separately, the CR rates were 92% for stages IA, IIA and 53% for stages IB, IIB, III A and B, IV A and B. Relapses occurred in 20% of the patients treated with four CEOP courses plus radiotherapy and in 31% of those who received nine CEOP courses because of the advanced stage of their disease. As of May 1994, the median follow-up was 42 months. If all of the patients are considered together, the 7-year overall survival (OS) probability was 64% and the 7-year disease-free survival (DFS) probability 67%. In comparison with stages III/IV, the patients in stages I-II had better DFS (7-year chance 77% vs 56%, p < 0.03). Hematological toxicity was acceptable, and a delay in the administration of CEOP chemotherapy was required in only three patients. No life-threatening infections were recorded. CONCLUSIONS Our cooperative study of the use of the CEOP combination in NHL patients shows that response rates and the length of DFS are equal to the best results obtained with CHOP and more intensive programs, although further confirmation must be provided by means of a longer follow-up and a more careful analysis of prognostic factors according to the recently proposed international index. In our experience, an EPI dose of 90 mg/m2 has negligible toxicity (particularly on bone marrow), even in elderly patients. These findings are interesting since it is well known that myelotoxicity is the principal limiting factor for the majority of anthracycline-containing regimens used in the treatment of potentially curable NHL.
Motivating Middle School Students to Revise and Edit

Describes how the author used research booklets to be read by sixth graders, poetry books, and taking part in a city-wide writing competition with her eighth-grade students to combat a general apathy in many students’ writing efforts. Suggests the projects spoke to individual interests, helped students find a purpose to write, and improved the quality of student work.
Cavity backed hi-lo stacked patch antennas

At previous symposia we have introduced edge-fed cavity backed patch antennas as an alternative to a conventional edge-fed configuration that overcomes several of the inherent issues associated with this architecture (W. S. T. Rowe et al., July 2006 and A. S. Elmezughi, et al., June 2007). We have shown both theoretically and experimentally that this dielectric filled cavity backed radiator has significantly higher efficiency and less pattern scalping than a traditional edge-fed patch for two reasons: (i) the cavity reduces the amount of surface wave propagation; and (ii) the thin substrate layer used to etch the feed network allows for a thinner track width to realize a 50 Omega characteristic impedance, and therefore reduces spurious radiation from the feed network. The new cavity backed edge-fed radiator shows a 3 dB improvement in the gain, and reduces the pattern undulation by 10 dB. The attributes of this architecture are particularly suited to large planar arrays, which is a prevalent application of edge-fed microstrip patches.
The Mentoring Manager: Strategies for Fostering Talent and Spreading Knowledge

Mentor - an experienced and trusted adviser Mentoring can be daunting when you first come across it. What is it for? How is it used? Mentoring is the most effective way to help people develop their jobs and careers. The challenge is to learn to apply it in a structured, thoughtful and planned way. This book will show you how to maximize your company's pool of knowledge and experience to benefit all concerned.
Successful Treatment of an Adolescent With Naegleria fowleri Primary Amebic Meningoencephalitis

Naegleria fowleri is a thermophilic, free-living ameba that causes primary amebic meningoencephalitis. The infections are nearly always fatal. We present the third well-documented survivor of this infection in North America. The patient’s survival most likely resulted from a variety of factors: early identification and treatment, use of a combination of antimicrobial agents (including miltefosine), and management of elevated intracranial pressure based on the principles of traumatic brain injury.
Lysosomes Behave as Ca2+-regulated Exocytic Vesicles in Fibroblasts and Epithelial Cells

Lysosomes are considered to be a terminal degradative compartment of the endocytic pathway, into which transport is mostly unidirectional. However, specialized secretory vesicles regulated by Ca2+, such as neutrophil azurophil granules, mast cell–specific granules, and cytotoxic lymphocyte lytic granules, share characteristics with lysosomes that may reflect a common biogenesis. In addition, the involvement of Ca2+ transients in the invasion mechanism of the parasite Trypanosoma cruzi, which occurs by fusion of lysosomes with the plasma membrane, suggested that lysosome exocytosis might be a generalized process present in most cell types. Here we demonstrate that elevation in the intracellular free Ca2+ concentration of normal rat kidney (NRK) fibroblasts induces fusion of lysosomes with the plasma membrane. This was verified by measuring the release of the lysosomal enzyme β-hexosaminidase, the appearance on the plasma membrane of the lysosomal glycoprotein lgp120, the release of fluid-phase tracers previously loaded into lysosomes, and the release of the lysosomally processed form of cathepsin D. Exposure to the Ca2+ ionophore ionomycin or addition of Ca2+containing buffers to streptolysin O–permeabilized cells induced exocytosis of ∼10% of the total lysosomes of NRK cells. The process was also detected in other cell types such as epithelial cells and myoblasts. Lysosomal exocytosis was found to require micromolar levels of Ca2+ and to be temperature and ATP dependent, similar to Ca2+-regulated secretory mechanisms in specialized cells. These findings highlight a novel role for lysosomes in cellular membrane traffic and suggest that fusion of lysosomes with the plasma membrane may be an ubiquitous form of Ca2+-regulated exocytosis.
Ridged Waveguide Slot Antenna Using High-Impedance Ground Plane

High-impedance surface (HIS) is a kind of electromagnetic bandgap (EBG) structure utilized as a ground plane for ridged waveguide slot antennas in order to improve their radiation characteristics. As compared to a solid metal ground plane, the results suggest that a high-impedance ground plane (HIGP) can significantly improve the patterns of the slot antennas: the back lobes are reduced, and the gains are increased. Furthermore, an 8-10-dB reduction in the mutual coupling of two single ridged waveguide antenna arrays than convention l metal ground plane.
Bearing fault detection using relative entropy of wavelet components and artificial neural networks

Fault detection in electrical machines have been widely explored by researchers, especially bearing faults that represents about 40% to 60% of the total faults. Since this kind of fault is detectable by particular frequencies at the stator current, it is now a source of investigation. Thus, this work presents a predicability analysis method based on relative entropy measures estimated over reconstructed signals obtained from wavelet-packet decomposition components. The signals were simulated using a real motor current signal with addition of frequency components related to the bearing faults. Using three ANN topologies, these entropy measures are classified in two groups: normal and faulty signals with a high performance rate.
Functional magnetic resonance imaging study of human olfaction and normal aging.

BACKGROUND The function of human olfaction declines with advancing age. An important question centers on whether functional alterations to olfactory brain structures accompany age-related behavioral changes. In the present study, we tested the hypothesis that aged adults have intact though reduced activity in the central olfactory system using functional magnetic resonance imaging (fMRI). METHODS University of Pennsylvania Smell Identification Test (UPSIT) was used to test the smell function of 11 young (23.9 +/- 1.6 years) and 8 aged (66.4 +/- 4.4 years) healthy participants. Then, the participants received fMRI at 3.0 T with lavender and spearmint as stimulants. After fMRI, the participants provided ratings for the odorants' intensity and pleasantness. RESULTS The average UPSIT score of the aged adults was 34.1 +/- 1.5, which was significantly lower than that of the young adults (37.3 +/- 1.1) (p =.0004). Both age groups showed significant activation in major olfactory brain structures, including the primary olfactory cortex, entorhinal cortex, hippocampus and parahippocampal cortex, thalamus, hypothalamus, orbitofrontal cortex, and insular cortex and its extension into the inferior lateral frontal region. The aged adults showed less brain activity in olfactory structures (p =.022), consistent with lower ratings of odor intensity and UPSIT scores. Activation intensity in bilateral primary olfactory cortex areas and right insular cortex was also comparatively weaker (p <.019). CONCLUSION Results demonstrate that significant activation in aged adults can be observed in all the olfactory brain structures that are activated in young adults, but with lower activation volume and intensity. This finding provides a necessary baseline for further investigations in olfaction and aging.
Higher-order optimal control design via singular perturbation

Control design is generally based on an approximate model of a real-life system. In this paper, a complex dynamical system is depicted using not one but several models of the same system. Based on interest for robust implementation of reduced-order controllers in higher-order models, we study the regulator problem for a dynamical system expressed as a framework of several models where the reduction between them is made by singular perturbation theory. This multiresolutional representation portrays the model and cost at different levels of complexity, allowing to study analytical solutions for the minimization problem at each level to determine cases in which the cost can be minimized without necessarily requiring an exact optimal control. As result, we show that sometimes a small improvement in the reduced-order optimal control may improve the minimum cost value for the high-order model in a significant way. A singularly perturbed quadratic regulator accounting for actuator dynamics expressed as the discontinuous nonlinearity sign in its structure is shown as example to illustrate these properties.
World-sheet scattering in AdS5 ? S5 at two loops

We study the AdS5 × S5 sigma-model truncated to the near-flat-space limit to two-loops in perturbation theory. In addition to extending previously known one-loop results to the full SU(2|2)2 S-matrix we calculate the two-loop correction to the dispersion relation and then compute the complete two-loop S-matrix. The result of the perturbative calculation can be compared with the appropriate limit of the conjectured S-matrix for the full theory and complete agreement is found.
Munchausen's Syndrome by Proxy: Current Issues in Assessment, Treatment and Research

A 20-year overview, A. Bentovim international perspectives on Munchausen's syndrome by proxy, R. Brown and M.D. Feldman child abuse specific to the medical system, J. Jureidini and T. Donald the extraordinary case of Mrs. H. , E.V. Welldon Munchausen's syndrome by proxy - a perspective from primary care, M.J. Bannon and Y.H. Carter the presentation and natural history of Munchausen's syndrome by proxy, M.C. B. Plunkett and D.P. Southall the detection of Munchausen's syndrome by proxy, M.P. Samuels assessment of abusing families, D.P.H. Jones and C. Newbold the role of the guardian ad litem, S. Pizzey the social work role in Munchausen's syndrome by proxy, J. Gray Munchausen's syndrome by proxy - the legal perspective, D. Taylor and M. Nicholls risk assessment, M. Eminson treatment of perpetrators, K. Bluglass treatment and outcome for victims, I. Mitchell ethical and public policy issues in the management of Munchausen's syndrome by proxy (MSBP), G. Adshead current challenges in the management of perpetrators, D. Brooke and G. ADshead new directions in research and service development, C. Bools.