Miracle-dz/UniFAR-FTUs huggingface dataset:
Epac2: A Molecular Target for Sulfonylurea-Induced Insulin Release

Epac2 is an intracellular receptor for a commonly used class of antidiabetic medications. Sulfonylurea drugs are used in type 2 diabetes mellitus therapy to induce release of endogenous insulin from pancreatic β cells. They act on sulfonylurea receptors, which are the regulatory subunits of adenosine triphosphate (ATP)–sensitive potassium ion (KATP) channels and cause channel closure to trigger exocytosis. Epac2 was identified as an intracellular target for sulfonylurea drugs, providing a potential nonelectrogenic signaling component to the mechanism of action for these agents. Commonly used sulfonylureas such as tolbutamide and glibenclamide induced Epac2 activation with distinct kinetic profiles. Epac2−/− mice failed to respond to sulfonylureas, suggesting that both sulfonylurea receptors and Epac2 are necessary for the action of these drugs. These data require that the cellular and physiological effects of drugs that alter the open state of the KATP channel be reassessed.
Informal Caregivers’ Learning Experiences With Self-Management Support of Individuals Living With Bipolar Disorder: A Phenomenological Study

BACKGROUND: The degree of informal caregiver involvement influences the self-management of individuals living with bipolar disorder (BD). OBJECTIVE: This article aims to provide a description of informal caregivers’ learning experiences in self-management support of BD in order to guide professionals in tailoring future psychosocial and psychoeducational interventions. DESIGN: In-depth open interviews with 10 informal caregivers of patients with BD who followed treatment in the context of specialized outpatient bipolar care were conducted. RESULTS: Four learning phases emerged from the phenomenological analysis describing the informal caregivers learning process: (1) understanding BD, (2) overcoming the dilemmas in self-management support for individuals living with BD, (3) dividing tasks and responsibilities, and (4) acquiring a personal definition of self-management support for individuals living with BD. CONCLUSION: By grasping the concept of BD, informal caregivers gradually learn how to overcome dilemmas resulting from living with someone with BD, and how to control the expression of emotions. They learn to reflect on the nature of conflicts and how to share the responsibilities of illness management with individuals living with BD and professionals. Mastering these skills eventually allows them to define and delimit their supporting informal caregiver role in the self-management of BD. PRACTICE IMPLICATIONS: Our findings provide information regarding the educational needs of informal caregivers to tailor counseling, and psychosocial and psychoeducational interventions in specialized outpatient care for individuals living with BD.
The CORDIC Trigonometric Computing Technique

The COordinate Rotation DIgital Computer(CORDIC) is a special-purpose digital computer for real-time airborne computation. In this computer, a unique computing technique is employed which is especially suitable for solving the trigonometric relationships involved in plane coordinate rotation and conversion from rectangular to polar coordinates. CORDIC is an entire-transfer computer; it contains a special serial arithmetic unit consisting of three shift registers, three adder-subtractors, and special interconnections. By use of a prescribed sequence of conditional additions or subtractions, the CORDIC arithmetic unit can be controlled to solve either set of the following equations: Y' = K(Y cos? + X sin? ) X' = K(X cos? - Y sin? ), or R = K? X2 + Y2 ? = tan-1 Y/X, where K is an invariable constant. This special arithmetic unit is also suitable for other computations such as multiplication, division, and the conversion between binary and mixed radix number systems. However, only the trigonometric algorithms used in this computer and the instrumentation of these algorithms are discussed in this paper.
Equipe interdisciplinar reduz infecção sanguínea relacionada ao cateter venoso central em Unidade de Terapia Intensiva Pediátrica

OBJECTIVE: To determine the impact of interdisciplinary interventions on central venous catheter-related bloodstream infections rates in a Pediatric Intensive Care Unit (PICU) and on the bloodstream infection organisms. METHODS: Interventional study type before-and-after. An educational program was performed and an interdisciplinary team of interventions was created. This team was formed by nurses and doctors of the PICU and of the Infection Control Committee. The interventions were composed by direct and indirect educational and procedural measures. Task-force interventions were developed from Jun/2003 to May/2004. This pre-intervention period (Phase 1) was compared with two post-intervention periods: Phases 2 (Jun/2004 to May/2005) and 3 (Jun/2005 to May/2006). Central venous catheter-related bloodstream infection rates during the three periods were compared by ANOVA, being significant p<0.05. RESULTS: 1,234 patients were studied from June 1st 2003 to May 31, 2006. The number of central venous catheter-related bloodstream infections was 22.72 per 1,000 catheter-days in Phase 1, and 6.81 and 5.87 in Phases 2 and 3 respectively (Phase 1 vs Phase 2 and 3; p<0.001). Gram-positive organisms were isolated in 57% of bloodstream infections in Phase 1, and 45 and 58% in Phases 2 and 3, respectively. CONCLUSIONS: The interdisciplinary educational approach and the central venous catheter insertion policies were effective to reduce central venous catheter-related bloodstream infections in the Pediatric Intensive Care Unit.
Sphingolipids: The Oil on the TRAFire That Promotes Inflammation

Lipid second messengers are required for signaling through tumor necrosis factor and Toll-like receptors. Tumor necrosis factor receptor (TNFR)–associated factors (TRAFs) control inflammatory and immune responses by acting downstream of TNFRs and Toll-like receptors (TLRs). TRAF2 in particular has been extensively studied for its involvement in signaling by TNF-α, the classic inflammatory cytokine. Because it has a RING finger, it has been suggested that TRAF2 acts as an E3 ubiquitin ligase that catalyzes the noncanonical Lys-63 (K63)–linked polyubiquitination of receptor-induced protein 1 (RIP1), which is an essential event in the activation of the IκB kinase complex and consequently nuclear factor κB. Furthermore, TRAF2 itself is subject to K63-linked polyubiquitination, a modification that is rapidly induced upon receptor ligation and was interpreted to be the result of self-ubiquitination. However, formal evidence that TRAF2 is an active E3 ubiquitin ligase was lacking. New evidence shows that sphingosine-1-phosphate (S1P), a sphingolipid that is synthesized during inflammatory responses, is an essential cofactor for TRAF2 ubiquitin ligase activity. S1P binds to TRAF2 and promotes TRAF2-mediated K63-linked RIP1 polyubiquitination, providing direct evidence that TRAF2 is an active E3 ubiquitin ligase and also introducing lipid second messengers into the realm of TNFR and TLR signaling.
Comparison of Axillary And Heating Block Methods of Activated Clotting Time (ACT) in Dogs

Summary The activated clotting time (ACT) is commonly used in veterinary medicine as an assessment of dysfunction within the intrinsic clotting cascade. Performing the test requires little technical expertise and no special equipment except for a heating block or constant temperature waterbath, neither of which is routinely found in veterinary practices. The purpose of this study was to determine whether performing the test using a human axilla as the heat source was accurate for both normal dogs and clinically ill dogs (with prolonged ACT’s), when compared to using a heating block as the heat source. The results of this study reveal that the axillary method of ACT determination has acceptable clinical agreement with the heating block method. Thus, the axillary method of ACT determination is an acceptable alternative when no constant temperature heating source is available.
Skip Techniques for High-Speed Carry-Propagation in Binary Arithmetic Units

After a very brief summary of the various well-known methods of expediting carry-propagation in binary arithmetic units, the paper discusses and develops the ``anticipated-carry'' or ``carry-skip'' technique originally due in decimal form to Babbage, much used in mechanical calculators and lately revived for use in binary units. Various degrees of refinement are possible. It appears that for a given expenditure, the technique results in a unit which is simpler and faster than those using one of the other techniques. Conversely in order to attain a given speed with given circuit elements, the skip technique appears to minimize the equipment requirement among the known speed-up techniques.
The adhesion GPCR BAI1 mediates macrophage ROS production and microbicidal activity against Gram-negative bacteria

A macrophage adhesion receptor that mediates internalization of Gram-negative bacteria also stimulates the machinery that kills them. Bacteria come to a sticky end Pattern recognition receptors (PRRs) detect microbial products and stimulate the innate immune response to infections. BAI1 is a G protein–coupled receptor of the adhesion GPCR family and is also a PRR that binds to lipopolysaccharide on the surface of Gram-negative bacteria to facilitate their internalization by macrophages. Billings et al. found that BAI1 triggered the killing of the internalized bacteria by stimulating the production of reactive oxygen species. When engaged by bacteria, BAI1 activated Rac1 to stimulate the activity of the NADPH oxidase complex Nox2 in macrophages. Mice deficient in BAI1 were inefficient at clearing Gram-negative bacteria and were likely to die from the infection. Together, these data suggest that BAI1 connects bacterial internalization with their killing. The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH oxidase complex is a critical component of the macrophage bactericidal machinery. We previously characterized brain-specific angiogenesis inhibitor 1 (BAI1), a member of the adhesion family of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs), as a PRR that mediates the selective phagocytic uptake of Gram-negative bacteria by macrophages. We showed that BAI1 promoted phagosomal ROS production through activation of the Rho family guanosine triphosphatase (GTPase) Rac1, thereby stimulating NADPH oxidase activity. Primary BAI1-deficient macrophages exhibited attenuated Rac GTPase activity and reduced ROS production in response to several Gram-negative bacteria, resulting in impaired microbicidal activity. Furthermore, in a peritoneal infection model, BAI1-deficient mice exhibited increased susceptibility to death by bacterial challenge because of impaired bacterial clearance. Together, these findings suggest that BAI1 mediates the clearance of Gram-negative bacteria by stimulating both phagocytosis and NADPH oxidase activation, thereby coupling bacterial detection to the cellular microbicidal machinery.
Astroglial networks promote neuronal coordination

Gap junction–linked astrocytes form a network that coordinates neuronal activity. Connected astrocytes help with coordination Astrocytes are glial cells in the nervous system that are interconnected by gap junctions formed by connexins. Gap junctions form regulated pores that enable the connected cells to function as a unit by rapidly passing cytosolic signals. By analyzing hippocampal slices from mice that were deficient for astroglial connexins, Chever et al. found that interconnected astrocytes coordinated bursts of neuronal activity over large regions, which contributed to the intensity of induced seizures. Indeed, mice with disconnected astrocytes had more frequent, but less severe, chemically induced seizures than normal mice. Thus, intercellular communication between astrocytes enhances the coordination of activity in neuronal networks. Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30– and connexin 43–deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs.
Can We Prevent Back Injuries?

Learning Objectives Back pain is one of the most significant health care issues in North America. It affects health/fitness professionals as well as their clients. Approximately 60% to 80% of individuals in that population will suffer from back pain at one point in their life. The objectives of this article are 1) to review the research on back injuries as it relates to risk factors, 2) discuss the mechanisms of injury, 3) provide an objective interpretation of back injury prevention, and 4) provide exercises that can be used to prevent back pain.
Introducing the biometric storyboards tool for games user research

Evaluating and communicating affective user experience in games is an important component of the growing field of games user research (GUR). An important goal for the game industry and researchers alike is the successful unification of physiological measurements and player experience reports to generate meaningful insights, which is challenging due to the varying natures of the data. In this paper, we present a tool that facilitates GUR with a method called Biometric Storyboards (BioSt). The tool allows GUR professionals to visualize relationships between changes in a player's physiological state, a player's self-reported experience, and in-game events. This paper focuses on the BioSt development stages and the final BioSt tool that we present to facilitate the creation implementation of BioSt and its analysis procedure.
Regulation of autophagy, NF-κB signaling, and cell viability by miR-124 in KRAS mutant mesenchymal-like NSCLC cells

The loss of microRNA miR-124 enables prosurvival autophagy signaling and metastatic features in KRAS mutant mesenchymal lung cancer cells. Subtype selectivity in cancer Activating mutations in the protein KRAS are common in non–small cell lung cancers (NSCLCs). However, tumors of the mesenchymal subtype of KRAS mutant NSCLC are not responsive to RAS pathway inhibitors. By comparing tumor samples and cell lines of epithelial and mesenchymal NSCLCs, Mehta et al. found that loss of the microRNA miR-124 in mesenchymal tumor cells enables increased abundance of autophagy and related proteins, which promoted cell survival. Introducing miR-124 or inhibiting autophagy in the mesenchymal tumor cells triggered their apoptosis. These findings identify alternative molecular targets for potentially treating this subtype of NSCLC. KRAS mutant non–small cell lung cancer (NSCLC) may be classified into epithelial or mesenchymal subtypes. Despite having the same “driver” mutation, mesenchymal NSCLCs are less responsive than are epithelial NSCLCs to inhibition of the RAS pathway. Identifying alternative networks that promote survival specifically in mesenchymal NSCLC may lead to more effective treatments for this subtype. Through their numerous targets in cellular signaling pathways, noncoding microRNAs (miRNAs) often function as tumor suppressors or oncogenes. In particular, some miRNAs regulate the epithelial-mesenchymal transition (EMT). We derived an EMT-related miRNA signature by profiling the abundance of miRNAs in a panel of epithelial (KE) or mesenchymal (KM) KRAS mutant NSCLC cell lines. This signature revealed a number of suppressed miRNAs in KM cell lines, including members of the miR-200 family, which can suppress tumor progression by inhibiting EMT. Reconstituting KM cells with one of these miRNAs, miR-124, disrupted autophagy and decreased cell survival by reducing the abundance of p62, which is both an adaptor for selective autophagy and a regulator of the transcription factor nuclear factor κB (NF-κB). Suppression of p62 by miR-124 correlated with reduced abundance of the autophagy activator beclin 1 (BECN1), the ubiquitin ligase TRAF6, and the NF-κB subunit RELA/p65. The abundance of miR-124 inversely correlated with the expression of BECN1 and TRAF6 in patient NSCLC samples. These findings reveal how the loss of miR-124 promotes cell survival networks in the aggressive mesenchymal subtype of KRAS mutant NSCLC, which might lead to improved subtype-selective therapeutic strategies for patients.
Quality of tomato slices disinfected with ozonated water

Fresh-cut industry needs novel disinfectant to replace the use of chlorine. Ozone is one of the most powerful oxidizing agents and is applied in gaseous or aqueous form for sanitation purposes. However, the strong oxidative effect could affect the nutritional and sensorial quality, in particular, when time of washing is extended. For that reason, the overall impact of ozonated water (0.4 mg/L) dipping applied during 1, 3 and 5 min compared to control washed in water during 5 min was studied in tomato slices stored during 14 days at 5 ℃. According to the results, ozonated water treatment of 3 min achieved the best firmness retention, microbial quality (mesophilic, psychrotrophic and yeas load) and reduced the consumption of fructose and glucose. The use of ozonated water did not affect the total acidity, pH, total solid soluble, organic acid as ascorbic, fumaric or succinic acid and the sensorial parameters, which were only affected by storage time. However, the poor appearance, aroma and overall quality obtained in all treatments prevented shelf life of 14 days and the quality at acceptable levels was established in 10 days at 5 ℃. It is recommended to wash tomato slices with 0.4 mg/L ozonated water for 3 min only. Extending treatment duration did not improve the microbiological quality, possibly due to the extra time permitting the ozone to react with other components of the fruit tissue, undermining the antimicrobial benefits.
Melhora da dor, do cansaço e da qualidade subjetiva do sono por meio de orientações de higiene do sono em pacientes com fibromialgia

OBJECTIVE: To evaluate the effectiveness of sleep hygiene instructions for women with fibromyalgia. MATERIALS AND METHODS: Seventy women with fibromyalgia completed the study. The assessment comprised the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), and a general questionnaire with personal data and lifestyle information. All patients received information about the disease and a sleep diary, but only the experimental group received the sleep hygiene instructions. Patients were asked to practice sleep hygiene, and, after three months, they were reevaluated by use of the same questionnaires. RESULTS: The mean age in the control group was 55.2 ±7.12 years, and, in the experimental group, 53.5 ±8.89 years (P = 0.392). The experimental group showed: a decrease in the pain Visual Analogue Scale values (P = 0.028), in fatigue (P = 0.021), and in the PSQI component 1 (P = 0.030); and a significant reduction in the difficulty falling asleep after waking up in the middle of the night (P = 0.031). The experimental group also showed an increase in the reporting percentage of "silent environment" (ranging from 42.9% to 68.6%), a decrease in the reporting percentage of "fairly quiet environment" (ranging from 40% to 22.9%), and a decrease in the reporting percentage of "noisy environment" (ranging from 17.1% to 8.6%). These changes facilitated falling asleep after waking up in the middle of the night. CONCLUSION: The sleep hygiene instructions allowed changing the patients' behavior, which resulted in pain and fatigue improvement, increased subjective quality of sleep, in addition to facilitating falling asleep after waking up in the middle of the night.
Quantitative Fluorescence Imaging Analysis for Cancer Biomarker Discovery: Application to β-Catenin in Archived Prostate Specimens

The surprising disparity between the number of protein-encoding genes (∼30,000) in the human genome and the number of proteins (∼300,000) in the human proteome has inspired the development of translational proteomics aimed at protein expression profiling of disease states. Translational proteomics, which offers the promise of early disease detection and individualized therapy, requires new methods for the analysis of clinical specimens. We have developed quantitative flourescence imaging analysis (QFIA) for accurate, reproducible quantification of proteins in slide-mounted tissues. The method has been validated for the analysis of β-catenin in archived prostate specimens fixed in formalin. QFIA takes advantage of the linearity of fluorescence antibody signaling for tissue epitope content, a feature validated for β-catenin in methacarn-fixed prostate specimens analyzed by reverse-phase protein array analysis and QFIA (r = 0.97). QFIA of β-catenin in formaldehyde-fixed tissues correlated directly with β-catenin content (r = 0.86). Application of QFIA in a cross-sectional study of biopsies from 42 prostate cancer (PC) cases and 42 matched controls identified β-catenin as a potential field marker for PC. Receiver operating characteristic plots revealed that β-catenin expression in the normal-appearing acini of cancerous glands identified 42% (95% confidence intervals, 26-57%) of cancer cases, with 88% (95% confidence intervals, 80-96%) specificity. The marker may contribute to a PC biomarker panel. In conclusion, we report the development and validation of a new method for fluorescence quantification of proteins in archived tissues and its application to archived specimens for an evaluation of β-catenin expression as a biomarker for PC. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1371–81)
Optimisation of oat milk formulation to obtain fermented derivatives by using probiotic Lactobacillus reuteri microorganisms

Functional advantages of probiotics combined with interesting composition of oat were considered as an alternative to dairy products. In this study, fermentation of oat milk with Lactobacillus reuteri and Streptococcus thermophilus was analysed to develop a new probiotic product. Central composite design with response surface methodology was used to analyse the effect of different factors (glucose, fructose, inulin and starters) on the probiotic population in the product. Optimised formulation was characterised throughout storage time at 4 ℃ in terms of pH, acidity, β-glucan and oligosaccharides contents, colour and rheological behaviour. All formulations studied were adequate to produce fermented foods and minimum dose of each factor was considered as optimum. The selected formulation allowed starters survival above 107/cfu ml to be considered as a functional food and was maintained during the 28 days controlled. β-glucans remained in the final product with a positive effect on viscosity. Therefore, a new probiotic non-dairy milk was successfully developed in which high probiotic survivals were assured throughout the typical yoghurt-like shelf life.