Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Cloning and Functional Characterization of Murine Sphingosine Kinase*

Sphingosine-1-phosphate (SPP) is a novel lipid messenger that has dual function. Intracellularly it regulates proliferation and survival, and extracellularly, it is a ligand for the G protein-coupled receptor Edg-1. Based on peptide sequences obtained from purified rat kidney sphingosine kinase, the enzyme that regulates SPP levels, we report here the cloning, identification, and characterization of the first mammalian sphingosine kinases (murine SPHK1a and SPHK1b). Sequence analysis indicates that these are novel kinases, which are not similar to other known kinases, and that they are evolutionarily conserved. Comparison withSaccharomyces cerevisiae and Caenorhabditis elegans sphingosine kinase sequences shows that several blocks are highly conserved in all of these sequences. One of these blocks contains an invariant, positively charged motif, GGKGK, which may be part of the ATP binding site. From Northern blot analysis of multiple mouse tissues, we observed that expression was highest in adult lung and spleen, with barely detectable levels in skeletal muscle and liver. Human embryonic kidney cells and NIH 3T3 fibroblasts transiently transfected with either sphingosine kinase expression vectors had marked increases (more than 100-fold) in sphingosine kinase activity. The enzyme specifically phosphorylatedd-erythro-sphingosine and did not catalyze the phosphorylation of phosphatidylinositol, diacylglycerol, ceramide,d,l-threo-dihydrosphingosine orN,N-dimethylsphingosine. The latter two sphingolipids were competitive inhibitors of sphingosine kinase in the transfected cells as was previously found with the purified rat kidney enzyme. Transfected cells also had a marked increase in mass levels of SPP with a concomitant decrease in levels of sphingosine and, to a lesser extent, in ceramide levels. Our data suggest that sphingosine kinase is a prototypical member of a new class of lipid kinases. Cloning of sphingosine kinase is an important step in corroborating the intracellular role of SPP as a second messenger.
Child Benefit Packages in 15 Countries in 2004

The book explores the implications of changes to the welfare state for children in a range of countries. Children, Changing Families and Welfare States: examines the implications of social policies for children; sets the discussion in the broader context of both family change and welfare state change, exploring the nature of the policy debate that has allowed the welfare of the child to come to the fore; tackles policies to do with both the care and financial support of children; looks at the household level and how children fare when both adult men and women must seek to combine paid and unpaid work, and what support is offered by welfare states; and endeavours to provide a comparative perspective on these issues.
Simple Strategic Analysis Tools at SMEs in Ecuador

This article explores the possible applications of Strategic Analysis Tools (SAT) in SMEs located in emerging countries such as Ecuador (where there are no formal studies on the subject). It is intended to analyze if whether or not it is feasible to effectively apply a set of proposed tools to guide mental map decisions of executives when decisions on strategy have to be made. Through an in-depth review of the state of the art in regards to SAT and interviews performed to main participants such as chambers and executives of different firms, it is shown the feasibility of their application. This analysis is complemented with specialists´ interviews to deepen our insights and obtaining valid conclusions. Our conclusion is that SMEs can smoothly develop and apply an appropriate set of SAT when opting for very relevant choices. However, there are some inconveniences to be solved which are connected with resources (such as peoples’ abilities and technology) and behavioral (cultural factors and methodological processes). Once these barriers are knocked down, it would be more likely to enrich current approaches to make strategic decisions even more effective. This is a qualitative investigation and the research design is not experimental (among them it is transversal as it relates to a specific moment in time).
Two weeks of repetitive gut‐challenge reduce exercise‐associated gastrointestinal symptoms and malabsorption

Debilitating gastrointestinal symptoms is a common feature of endurance running and may be exacerbated by and/or limit the ability to tolerate carbohydrate intake during exercise. The study aimed to determine whether two weeks of repetitive gut‐challenge during running can reduce exercise‐associated gastrointestinal symptoms and carbohydrate malabsorption. Endurance runners (n=18) performed an initial gut‐challenge trial (GC1) comprising 2‐hour running exercise at 60% VO2max (steady state) while consuming a formulated gel‐disk containing 30 g carbohydrates (2:1 glucose‐fructose, 10% w/v) every 20 minutes, followed by a 1‐hour running effort bout. Gastrointestinal symptoms, feeding tolerance, and breath hydrogen (H2) were determined along the gut‐challenge trial. After GC1, participants were randomly assigned to a blinded carbohydrate (CHO, 90 gCHO hour−1) or placebo (PLA, 0 gCHO hour−1) gut‐training group. This comprised of consuming the group‐specific feeding intervention during 1‐hour running exercise at 60% VO2max equivalent, daily over a period of two weeks. Participants then repeated the gut‐challenge trial (GC2). In GC2, a reduced gut discomfort (P=.012), total (P=.009), upper‐ (P=.015), and lower‐gastrointestinal (P=.008) symptoms, and nausea (P=.05) were observed on CHO, but not PLA. Feeding tolerance did not differ between GC1 and GC2 on CHO and PLA. H2 peak was attenuated in GC2 (6±3 ppm) compared to GC1 (13±6 ppm) on CHO (P=.004), but not on PLA (GC1 11±7 ppm, and GC2 10±10 ppm). The effort bout distance was greater in GC2 (12.3±1.3 km) compared with GC1 (11.7±1.5 km) on CHO (P=.035) only. Two weeks of repetitive gut‐challenge improve gastrointestinal symptoms and reduce carbohydrate malabsorption during endurance running, which may have performance implications.
HSP70 modified response against HPV based tumor.

BACKGROUND AND OBJECTIVES DNA immunization is quite inventive vaccination strategies that engage the direct introduction of plasmid DNA encoding the desired antigen into the host. DNA vaccines expand strong protective responses against tumors. The desired target E7 oncogene products represent a target of choice for the therapeutic vaccination. The efficacy of vaccination is limited and it is often necessary to enhance the immune response by using adjuvant in order to achieve the desired responses. Numerous approaches have been applied to boost the effectiveness, such as the fusion or co-administration of cytokine and co-stimulatory molecules gene. Heat-shock protein 70 a family of chaperone proteins makes possible delivery of non-covalently bound peptide to MHC I molecules and influences peptide-specific CTL responses and cure treated individuals. HSP70 have been proposed as the affective adjuvant and expected to act as an appropriate substitute of both cytokine and co-stimulatory genes. MATERIALS AND METHODS In the current study, the impact of HSP70 co-delivery and HPV-E7 boosting on cellular immune responses and protection has been investigated by intramuscular injection of mixed DNA constructs. RESULTS Our results reveal that the target DNA vaccine can influence an E7-specific CTL response, which is imperative in the lysis of infected tumor cells, compared to negative control (p < 0.05). Additionally, treatment of tumor-bearing mice with pcDNA/E7 + HSP70 plasmid generates stronger immune responses and decreased significantly tumor sizes. Immunization with HSP-based vaccine with special target immunogene can induce potent and specific anti-tumor or anti-viral immune responses. CONCLUSIONS Co-administration of pcDNA/E7 + HSP70 plasmid was immunologically more effective than pcDNA/E7 alone. It was concluded that all the characteristics observed during our investigation demonstrate the potent adjuvant activities of HSP70 and could be an efficient approach to persuade dramatically E7-specific immune responses as future cervical cancer vaccine.
Stimulation of Insulin Release by Non-Sulfonylurea Hypoglycemic Agents: The Meglitinide Family

Several new non-sulfonylurea hypoglycemic agents such as A-4166, KAD-1229 and repaglinide are structurally related to meglitinide, previously known as the non-sulfonylurea moiety of glibenclamide, or its analog S 3075. There is no parallelism between the ionophoretic and insulinotropic efficiency of these compounds. They are all able, however, to decrease K+ conductance in islet cells as documented by a decrease in 86Rb outlfow from prelabelled pancreatic islets. In terms of concentrations of equal insulinotropic capacity, a difference of at least two orders of magnitude is observed between the weakest (meglitinide) and most potent (S 3075) compound. All these agents exert little effect upon insulin release in nutrient-deprived islets, but markedly augment glucose-stimulated insulin release. The hexose can be replaced, however, by a non-glucidic nutrient such as the methyl ester of succinic acid to support the insulinotropic action of the meglitinide analogs. The question is raised as to the potential advantage of these non-sulfonylurea insulinotropic agents over hypoglycemic sulfonylureas.
Benefit of a favorable cardiovascular risk-factor profile in middle age with respect to Medicare costs.

BACKGROUND People without major risk factors for cardiovascular disease in middle age live longer than those with unfavorable risk-factor profiles. It is not known whether such low-risk status also results in lower expenditures for medical care at older ages. We used data from the Chicago Heart Association Detection Project in Industry to assess the relation of a low risk of cardiovascular disease in middle age to Medicare expenditures later in life. METHODS We studied 7039 men and 6757 women who were 40 to 64 years of age when surveyed between 1967 and 1973 and who survived to have at least two years of Medicare coverage in 1984 through 1994. Men and women classified as being at low risk for cardiovascular disease were those who had the following characteristics at the time they were initially surveyed: serum cholesterol level, <200 mg per deciliter (5.2 mmol per liter); blood pressure, < or =120/80 mm Hg; no current smoking; an absence of electrocardiographic abnormalities; no history of diabetes; and no history of myocardial infarction. We compared Medicare costs for the 279 men (4.0 percent) and 298 women (4.4 percent) who had this low-risk profile with those for the rest of the study group, who were not at low risk. Health Care Financing Administration charges for services to Medicare beneficiaries were used to estimate average annual health care costs (total costs, those for cardiovascular diseases, and those for cancer). RESULTS Average annual health care charges were much lower for persons at low risk - the total charges for the men at low risk were less than two thirds of the charges for the men not at low risk ($1,615 less); for the women at low risk, the charges were less than one half of those for the women not at low risk ($1,885 less). Charges related to cardiovascular disease were lower for the low-risk groups of men and women than for those not at low risk (by $979 and $556, respectively), and charges related to cancer were also lower (by $134 and $189). CONCLUSIONS People with favorable cardiovascular risk profiles in middle age had lower average annual Medicare charges in older age. Having optimal status with respect to major cardiovascular risk factors may result not only in greater longevity but also in lower health care costs.
How to be at the right place at the right time: The importance of spindle positioning in embryos

Spindle positioning is an imperative cellular process that regulates a number of different developmental events throughout embryogenesis. The spindle must be properly positioned in embryos not only for the segregation of chromosomes, but also to segregate developmental determinants into different daughter blastomeres. In this review, the role of spindle positioning is explored in several different developmental model systems, which have revealed the diversity of factors that regulate spindle positioning. The C. elegans embryo, the Drosophila neuroblast, and ascidian embryos have all been utilized for the study of polarity‐dependent spindle positioning, and exploration of the proteins that are required for asymmetric cell division. Work in the sea urchin embryo has examined the influence of cell shape and factors that affect secondary furrow formation. The issue of size scaling in extremely large cells, as well as the requirement for spindle positioning in developmental fate decisions in vertebrates, has been addressed by work in the Xenopus embryo. Further work in mouse oocytes has examined the roles of actin and myosin in spindle positioning. The data generated from these model organisms have made unique contributions to our knowledge of spindle positioning. Future work will address how all of these different factors work together to regulate the position of the spindle. Mol. Reprod. Dev. 81: 884–895, 2014. © 2014 Wiley Periodicals, Inc.
Pacopampa: Early evidence of violence at a ceremonial site in the northern Peruvian highlands

Objectives Pacopampa, a ceremonial complex in Peru’s northern highlands, reveals early evidence of trauma in the Middle to Late Formative Period coinciding with the emergence of social stratification in the area. We examine the prevalence of trauma in human remains found at the site and present evidence of the circumstances surrounding the deaths of individuals who lived during the early stages of Andean civilization. Materials and methods The materials are the remains of 104 individuals (38 non-adult and 66 adult) from the Middle to Late Formative Periods. We explored trauma macroscopically and recorded patterns based on skeletons’ locations, age at death, sex, social class, and chronology. Results We detected trauma in remains over the Middle to Late Formative Periods. While the prevalence of trauma was minimal in the Middle Formative Period, skeletons from the subsequent era exhibit more severe disturbances. However, all the skeletons show signs of healing and affected individuals experienced a low degree of trauma. Discussion Given the archaeological context (the remains were recovered from sites of ceremonial practices), as well as the equal distribution of trauma among both sexes and a lack of defensive architecture, it is plausible that rituals, rather than organized warfare or raids, caused most of the exhibited trauma. Pacopampa was home to a complex society founded on ritual activity in a ceremonial center: this is indicated by the presence of ritual violence in a society that built impressively large, ceremonial architecture and developed social stratification without any political control of surplus agricultural goods.
[Acupuncture contra antiphlogistics in acute lumbago].

BACKGROUND Acute low back pain is one of the most frequent complaints presented in general practice. This study compares acupuncture and antiphlogistica in the treatment of acute low back pain in general practice. MATERIAL AND METHODS Among 60 consecutively included patients with acute low back pain, 30 patients were randomized to standardised acupuncture treatment for two weeks, and 30 patients to entero-soluble naproxen 500 mg twice daily for ten days. Effects were observed over six months, and observed for a further 12 months with regard to relapse of low back pain and number of days on sickness leave. RESULTS There were no differences in pain or stiffness (VAS, physical tests) at inclusion, nor in the reduction of pain or stiffness over a six month evaluation. However, patients receiving acupuncture used significantly less analgetic drugs during the first week after start of treatment than those receiving naproxen (2/28 versus 11/29, p < 0.01). Patients receiving acupuncture also reported fewer new episodes of low back pain (11/28 versus 30/29, p < 0.05) during the 6 + 12 month follow-up. Side effects were frequent in the naproxen group, especially gastro-enteric side effects (0/28 versus 15/29, p < 0.01). INTERPRETATION Standardised acupuncture treatment seems to be safe and effective in the treatment of acute low back pain in general practice.
A New Approach to $H_{\infty}$ Filter Design for Systems With Time-Varying State Delay

This brief revisits the robust H∞ filter design problem for systems with a time-varying state delay by an indirect approach. By employing a two-term approximation method, the filtering error system with a time-varying delay is reformulated into a feedback interconnection form, which contains a forward system with two constant time delays and a feedback system with uncertainties. Then, based on the scaled small gain theorem, the asymptotic stability of the filtering error system is examined, and a new delay-dependent bounded real lemma (BRL) is obtained. Based on the BRL, both the full- and reduced-order filter design approaches are proposed. Moreover, immediate extensions of the results are made to systems with polytopic uncertainties. Finally, two illustrative examples are presented to demonstrate the validity of the proposed methods.
Exercise Heat Stress does not Reduce Central Activation to non‐exercised Human Skeletal Muscle

In this study we measured the central activation ratio (CAR) of the leg extensors and the elbow flexor muscles before and after exhaustive exercise in the heat to determine whether exercise‐induced hyperthermia affects the CNS drive to exercised (leg extensors) and/or non‐exercised (forearm flexors) muscle groups. Thirteen subjects exercised at fixed intensities representative of a percentage of peak power output (PPO) for 10 min periods (50%, 40%, 60%, 50%) and then at 75% PPO until exhaustion in ambient conditions of 39.3 ± 0.8 °C and 60.0 ± 0.8% relative humidity. Before and immediately following exercise subjects performed a series of maximal voluntary contractions (MVCs) with the leg extensors (exercised muscles) and forearm flexors (non‐exercised muscles). The degree of voluntary activation during the sustained MVCs was assessed by superimposing electrical stimulation to the femoral nerve and the biceps brachii. Exercise to exhaustion increased the rectal temperature from 37.2 ± 0.2 to 38.8 ± 0.2 °C (P < 0.0001). The mean heart rate at the end of exercise to exhaustion was 192 ± 3 beats min−1. Leg extensor voluntary force was significantly reduced from 595 ± 143 to 509 ± 105 N following exercise‐induced hyperthermia but forearm flexor force was similar before and after exercise. The CAR of the leg extensors decreased from 94.2 ± 1.3% before exercise to 91.7 ± 1.5% (P < 0.02) following exercise‐induced hyperthermia. However, the CAR for the forearm flexors remained at similar levels before and after exercise. The data suggest that the central nervous system selectively reduces central activation to specific skeletal muscles as a consequence of exercise‐induced hyperthermia.
Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.

BACKGROUND Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix. METHODS The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer. RESULTS The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term. CONCLUSIONS Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.
Positioning centrosomes and spindle poles: looking at the periphery to find the centre

Centrosome positioning is tightly controlled throughout the cell cycle and probably shares common regulatory mechanisms with spindle‐pole positioning. In this article, we detail the possible mechanisms controlling centrosome and spindle positioning in various organisms both in interphase and mitotic cells, and discuss recent findings showing how microtubule plus‐end‐associated proteins interact with the cell cortex. We suggest that microtubule plus‐end complexes simultaneously regulate microtubule dynamics and microtubule anchoring at the cell periphery to allow proper centrosome and spindle‐pole positioning.
Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation

Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the early stage, RANK signaling is mediated by recruiting adaptor molecules such as tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of mitogen-activated protein kinases (MAPKs), and the transcription factors nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Activated NF-κB induces the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate stage of signaling, the co-stimulatory signal induces Ca2+ oscillation via activated phospholipase Cγ2 (PLCγ2) together with c-Fos/AP-1, wherein Ca2+ signaling facilitates the robust production of NFATc1. In the late stage of osteoclastogenesis, NFATc1 translocates into the nucleus where it induces numerous osteoclast-specific target genes that are responsible for cell fusion and function.
Numerical analysis on the net Gross MISO-SFNG in DVB-T2 system

In this study, a step-by-step analysis on the net Gross single-input single-output single frequency network gain (SISO-SFNG) is presented. The net gain is calculated by subtracting the net gain of a MISO-SFN from that of a multiple-input singleoutput (MISO)-SFN. In order to predict the service coverage of SFN accurately, it is required to calculate the corresponding SFN gain accurately in the receive signal overlapping area of the SFN. Analytical formulas are derived to calculate the net gains of SISO-SFN and MISO-SFN as a function of the signal amplitude and delay spread at each receive point of SFN. Validity of the derived formulas is confirmed by comparing the numerical analysis results with the measurement data in the related studies. Finally, we exemplify a practical application of the derived formula to predict the net gain of MISO-SFN system by using the reference network with a reference planning configuration.