Miracle-dz/UniFAR-FTUs huggingface dataset:
When to stop a clinical trial.

certain dates, must comply with agreed European or national standards. These new regulations will operate alongside some of the existing legislation, such as the Control of Substances Hazardous to Health Regulations, which already require employers to protect employees from such hazardous substances as glutaraldehyde, anaesthetic gases, infected blood, and other body tissues.4 Accident and emergency staff who do not wear suitable personal protective equipment may therefore be in breach of new health and safety legislation, specifically the Personal Protective Equipment at Work Regulations and, generally, the Health and Safety at Work, etc, Act 1974 and the proposed "general provisions" regulations. It is rumoured that when the general provisions regulations are finally agreed they will be renamed the Management of Health and Safety at Work Regulations, which would put the onus of compliance for health and safety on management.
Adiponectin and adiponectin receptor genes are coexpressed during zebrafish embryogenesis and regulated by food deprivation

Adiponectin is an adipocytokine that plays important roles in glucose and lipid homeostasis. Adiponectin binds to two types of transmembrane receptors: Adiponectin receptor (AdipoR) type 1 and 2. We isolated and characterized the two adiponectin genes (adiponectin A and B) and the three adiponectin receptors in zebrafish. In adult, adiponectin A is only detected in the kidney while adiponectin B mRNAs are widely expressed and are detected in the liver, adipose tissue, muscle, and brain. The receptors are found in many tissues such as the brain, gut, liver, adipose tissue, kidney, and ovary. Interestingly, we detect embryonic synexpression of all genes in the pharyngeal region. We observed that adiponectin B expression in adult liver is reduced while the expression of the receptors is increased in fasted fish. These data indicate that the upstream members of the Adiponectin pathway have complex expression patterns and are regulated by food deprivation in zebrafish. Developmental Dynamics 237:1682–1690, 2008. © 2008 Wiley‐Liss, Inc.
Fuel-Mediated Teratogenesis and Breastfeeding

About 30 years ago, Norbert Freinkel and Boyd Metzger introduced a seminal hypothesis into developmental medicine and diabetes research. The fuel-mediated teratogenesis concept says that prenatal exposure to increased levels of “mixed nutrients,” especially increased glucose, and the corresponding increase in fetal insulin have immediate as well as long-lasting deleterious consequences for the offspring of diabetic mothers (1,2). In fact, this paradigm became a kind of forerunner of today's rapidly expanding fields of “perinatal programming” and “developmental origins of health and disease. ” It has variously been proven to be valid and has even been extended to the case of maternal overweight during pregnancy (3). Accordingly, exposure to maternal gestational diabetes mellitus (GDM) and overweight is meanwhile one of the best proven paradigms concerning the long-term impact of perinatal programming (4,5). It is crucial for the concept of fuel-mediated teratogenesis that altered food supply during critical periods of early development gives rise to lasting deleterious consequences. Differentiation and maturation, however, of affected organs and systems, such as pancreas, adipose tissue, and brain, are not finished at birth (2). The question therefore arises whether a prolongation of these critical exposures into the neonatal period might have similar effects. Colostrum is already produced during the last trimester of gestation. The composition of early breast milk reflects metabolic changes that occur in GDM (6). Moreover, in a considerable number of women with GDM, glucose metabolism does not completely normalize after pregnancy (7). Studies suggest that breast milk from women with diabetes contains, for example, increased levels of glucose and insulin as compared with breast milk from healthy mothers (6,8,9). Moreover, it has been shown that not only glucose but even hormones like insulin and leptin are absorbed from milk in the immature gut of an …
Modeling and nonlinear control of magnetic levitation systems

In this paper, the authors propose a nonlinear model for magnetic levitation systems which is validated with experimental measurements. Using this model, a nonlinear control law based on differential geometry is firstly synthesized. Then, its real-time implementation is developed. In order to highlight the performance of the proposed control law, experimental results are given.
LP Relaxation of the Potts Labeling Problem Is as Hard as Any Linear Program

In our recent work, we showed that solving the LP relaxation of the pairwise min-sum labeling problem (also known as MAP inference in graphical models or discrete energy minimization) is not much easier than solving any linear program. Precisely, the general linear program reduces in linear time (assuming the Turing model of computation) to the LP relaxation of the min-sum labeling problem. The reduction is possible, though in quadratic time, even to the min-sum labeling problem with planar structure. Here we prove similar results for the pairwise min-sum labeling problem with attractive Potts interactions (also known as the uniform metric labeling problem).
The Grammar of hitting, breaking, and cutting in Kimaragang Dusun

The hit, break, and cut classes of verbs are grammatically relevant in Kimaragang, as in English. The relevance of such classes for determining how arguments are expressed suggests that the meaning of a verb is composed of (a) systematic components of meaning (the event template); and (b) idiosyncratic properties of the individual root. Assuming this approach to be essentially correct, I compare grammatical phenomena in Kimaragang that are sensitive to verb class membership with phenomena that are not class-sensitive. The tendency that emerges is that class-sensitive alternations do not seem to be affix-dependent, and are quite restricted in their ability to introduce new arguments into the argument structure.
An investigation on the stability of n-D Lur'e systems

Necessary and sufficient conditions for the existence of a common piecewise quadratic Liapunov function for n-D single variable Lur'e systems are stated in terms of LMI's and a sufficient condition is stated in terms of a frequency domain inequality. Hence a simple analytic necessary condition for absolute stability of n-D systems is established. Numerical evidence is presented to establish the absolute stability of a class of third order Lur'e systems
The 43 , 000 Growth-associated Protein Functions as a Negative Growth Regulator in Glioma 1

Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocytoma formation and progression. In an effort to identify novel gene expression changes associated with astrocytoma formation, which might reveal new potential targets for glioma therapeutic drug design, we used the B8-RAS-transgenic mouse astrocytoma model. Using multiplex gene expression profiling, we found that growth-associated protein 43 (GAP43) RNA and protein expression were lost in select human and mouse glioma cell lines. In this study, we demonstrate that re-expression of GAP43 in deficient C6 glioma cells results in growth suppression in clonogenic assays, as well as in multiple independently derived C6 glioma cell lines in vitro. GAP43-expressing C6 cells also exhibit reduced tumor growth as s.c. explants in immunocompromised mice in vivo. In addition, GAP43-expressing C6 clones demonstrate impaired cell motility and increased homophilic aggregation. GAP43 re-expression is also associated with reduced mitogen-activated protein kinase and AKT activation in C6 cells, suggesting that GAP43 functions as a novel glioma growth suppressor by modulating mitogenic signaling pathways.
Efficacy of Trovafloxacin against Experimental Staphylococcus aureus Endocarditis

ABSTRACT Trovafloxacin is a new fluoronaphthyridone chemically and functionally related to members of the fluoroquinolone class of antimicrobial agents. The in vivo efficacy of the drug was compared with that of vancomycin by using the rabbit model of left-sided endocarditis. Rabbits infected with either a nafcillin-susceptible or -resistant test strain were treated with trovafloxacin (13.3 mg/kg of body weight every 12 h) or vancomycin (25 mg/kg of body weight every 8 h) for 4 days. In comparison with untreated controls, both antimicrobial agents effectively cleared bacteremia and significantly reduced bacterial counts in vegetations and tissues of animals infected with either test strain. No resistance to trovafloxacin emerged in test strains during therapy. We conclude that in this model trovafloxacin is as efficacious as vancomycin is and may serve as a viable alternative to vancomycin for use in humans with similar infections.
Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

Objective. Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under conditions following good manufacturing practice (GMP). The aims of the study were first to establish culture conditions following GMP quality demands for human MSC expansion and differentiation for use in clinical trials, and second to compare these MSCs with MSCs derived from culture in four media commonly used for MSC cultivation in animal studies simulating clinical stem cell therapy. Material and methods. Human mononuclear cells (MNCs) were isolated from BM aspirates by density gradient centrifugation and cultivated in a GMP‐accepted medium (EMEA medium) or in one of four other media. Results. FACS analysis showed that the plastic‐adherent MSCs cultured in EMEA medium or in the other four media were identically negative for the haematopoietic surface markers CD45 and CD34 and positive for CD105, CD73, CD90, CD166 and CD13, which in combined expression is characteristic of MSCs. MSC stimulation with vascular endothelial growth factor (VEGF) increased expression of the characteristic endothelial genes KDR and von Willebrand factor; the von Willebrand factor and CD31 at protein level as well as the capacity to develop capillary‐like structures. Conclusions. We established culture conditions with a GMP compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease.
Epicutaneous Immunotherapy Using a New Epicutaneous Delivery System in Mice Sensitized to Peanuts

Background: Peanut allergy is a life-threatening condition for which new efficient and safe treatment is expected. We evaluated epicutaneous immunotherapy (EPIT) as a new alternative treatment for peanut allergy in sensitized mice. Methods: Sixty BALB/c mice were sensitized by gavages with peanut protein extract (PPE) mixed with cholera toxin. An epicutaneous delivery system, coated with 100 µg PPE (Viaskin®, DBV Technologies, Paris, France), was applied to intact skin every week during 48 h (EPIT; n = 20). This group was compared with sensitized mice treated with subcutaneous immunotherapy (SCIT; n = 20), untreated sensitized mice (sham, n = 20), and naive mice (naive; n = 20). After the 8-week treatment, a histamine release test, airway hyperreactivity measurement by plethysmography, and a resistance-compliance measurement after the challenge were performed. Blood and bronchoalveolar lavage were sampled for serology, cytokines, and cytology. Results: Specific IgE (sIgE) increased after sensitization in the EPIT (0.26 µg/ml) and SCIT (0.21 µg/ml) groups and decreased after treatment (0.09 µg/ml, p < 0.001 and 0.06 µg/ml, p < 0.001, respectively). The IgG1/IgG2a ratio decreased in the EPIT and SCIT groups versus the sham group (3.7; p < 0.001 and 2.7; p < 0.01 and 15.1, respectively). At the higher metacholine concentration, enhanced pause values were lower in the EPIT and SCIT groups than in the sham group (7.29, 6.74, and 10.99, p < 0.01, respectively), and did not differ from that of the naive group (5.06). Resistance-compliance was reversed in the treated groups versus the sham group (p < 0.001). IL-4, IL-5, IL-13, eotaxin, and eosinophils were reduced in the BAL of the EPIT and SCIT groups versus the sham group (p < 0.001). Conclusion: In peanut-sensitized mice, based on biological and physiological responses, EPIT is as efficient as subcutaneous treatment which is the reference method in immunotherapy.
Enhancing soccer robot movement accuracy using omnidirectional wheel

Capabilities to make decisions of its movement and to move accurately are undoubtedly very important for robot soccer. Elaboration of robot soccer design with omnidirectional motion capability to enhance the robot movement accuracy is reported in this paper. The implementation and simulation of basic decision support system to determine robot movement according to their current environment is also reported. Experiments show that the robot is able to move accurately both in forward and rotational directions. For forward direction 3.33% and 4% of error in x-axis and y-axis, respectively are obtained, whereas average error of 2.111 for 15° and 2.22 for 135° in counter-clockwise direction, and 6.413 for 15° and 5.077 for 135° in clockwise direction is obtained for rotational direction.
Aspects of wind energy characteristics in transmission related optimisation models: Invited panel discussion paper

This invited panel paper discussion will outline a number of aspects of wind energy characteristics relevant to the optimal wind/transmission model formulation task. Optimal placement of wind capacity on a constrained transmission network is a typical example of this type of problem. In particular the relevance of advanced and computationally intensive stochastic unit commitment to the model formulation will be debated. Optimization constraint matrix structure and techniques to exploit it will be shown to be of considerable importance for this type of problem. The relative merits of different model dimensionality reduction schemes, either through multivariate component analysis and probability discretisation or indeed scenario reduction, will be discussed. A pragmatic acceptance of the imprecise impact of long-term power system uncertainties will be maintained throughout, and wherever possible generality to different types of power systems will be considered.
THE HYPEREOSINOPHILIC SYNDROME: Analysis of Fourteen Cases With Review of The Literature

Several closely related disease entities make up the idiopathic hypereosinophilic syndrome (HES). The syndrome is manifest by persistent and prolonged eosinophilia with organ damage. A group of 14 patients had hematologic, cardiac, and neurologic abnormalities attributable to this disease. Patient survival and response to chemotherapy was significantly better in this group than in previously reported patients. The etiology of HES remains unknown, as does the mechanism of tissue damage.
A 16-Residue Peptide Fragment of Macrophage Migration Inhibitory Factor, MIF-(50–65), Exhibits Redox Activity and Has MIF-like Biological Functions*

Macrophage migration inhibitory factor (MIF) is a cytokine that participates in the host inflammatory response. A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein oxidoreductase activity of MIF is associated with certain biological functions. Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some biochemical properties of the full-length protein. We report on the characterization of CXXC-spanning MIF-(50–65) and its serine variant, C57S/C60S-MIF-(50–65). Following disulfide-mediated cyclization, MIF-(50–65) adapted a β-turn conformation comparable with that of β-turn-containing cyclo-57,60-[Asp57,Dap60]MIF-(50–65). MIF-(50–65) had a redox potential E′0 of –0.258 V and formed mixed disulfides with glutathione and cysteine. MIF-(50–65) but not C57S/C60S-MIF-(50–65) had oxidoreductase activity in vitro. Intriguingly, MIF-(50–65) exhibited MIF-like cellular activities. The peptide but not its variant had glucocorticoid overriding and proliferation-enhancing activity and stimulated ERK1/2 phosphorylation. MIF-(50–65) and its variant bound to the MIF-binding protein JAB1 and enhanced cellular levels of p27Kip1. As the peptide and its variant were endocytosed at similar efficiency, sequence 50–65 appears sufficient for the JAB1-related effects of MIF, whereas other activities require CXXC. Cyclo-57,60-[Asp57,Dap60]MIF-(50–65) activated ERK1/2, indicating that CXXC-dependent disulfide and β-turn formation is associated with an activity-inducing conformation. We conclude that CXXC and sequence 50–65 are critical for the activities of MIF. MIF-(50–65) is a surprisingly short sequence with MIF-like functions that could be an excellent molecular template for MIF therapeutics.
Prediction of similarly-acting cis-regulatory modules by subsequence profiling and comparative genomics in D . melanogaster and D . pseudoobscura

Motivation: To date, computational searches for cis-regulatory modules (CRMs) have relied on two methods. The first, phylogenetic footprinting, has been used to find CRMs in non-coding sequence, but does not directly link DNA sequence with spatio-temporal patterns of expression. The second, based on searches for combinations of transcription factor (TF) binding motifs, has been employed in genome-wide discovery of similarly acting enhancers, but requires prior knowledge of the set of TFs acting at the CRM and the TFs’ binding motifs. Results: We propose a method for CRM discovery that combines aspects of both approaches in an effort to overcome their individual limitations. By treating phylogenetically footprinted non-coding regions (PFRs) as proxies for CRMs, we endeavor to find PFRs near co-regulated genes that are composed of similar short, conserved sequences. Using Markov chains as a convenient formulation to assess similarity, we develop a sampling algorithm to search a large group of PFRs for the most similar subset. When starting with a set of genes involved in Drosophila early blastoderm development and using phylogenetic comparisons of D. melanogaster and D. pseudoobscura genomes, we show here that our algorithm successfully detects known CRMs. Further, we use our similarity metric, based on Markov chain discrimination, in a genome-wide search, and uncover additional known and many candidate early blastoderm CRMs. Availability: Software is available via http://arep.med.harvard.edu/enhancers Contact: see http://arep.med.harvard.edu/email.html Supplementary Information: Can be accessed at http://arep.med.harvard.edu/enhancers
Effect of oxygen supplementation in a hatchery at high altitude and growth performance of broilers reared at low altitude

The objective of this study was to investigate the effect of oxygen supplementation on broiler eggs in a hatchery at high altitude on the growth performance and ascites syndrome of broilers reared at low altitude. The treatment groups were low altitude with no oxygen supplemented in the hatchery (LA-NOX); high altitude with oxygen supplementation in the hatchery (HA-OX); and high altitude with no oxygen supplemented in the hatchery (HA-NOX) group. Growth performance, heart weight, the concentrations of the hormones, T3, T4, T3/T4, and and plasma concentrations of haematocrit, haemoglobin, glucose and parameters of ascites syndrome during the growing period were investigated. A total of 243 one-day-old broilers were used for this study. During the growing period, excluding days 7, 28 and 35, oxygen supplementation at high altitude did not affect the live weight of broilers compared with the HA-OX and HA-NOX groups. The cumulative feed consumption was determined to be lower in the LA-NOX group and the same in the HA-OX and HA-NOX groups on the 42nd day. Between 21 and 42 days old, the LA-NOX group had a better feed conversion ratio (FCR) than the HA-OX and HA-NOX groups. Chick weight (CW), yolk sac weight (YSW) and chick heart weight (CHW) were higher in the LA-NOX group than in the HA-OX and HA-NOX groups. At 42 days old, there were no differences between the groups in heart weight, right ventricle weight (RV), left ventricle and septum (LV+Sept.), total ventricle (TV) weight and the RV : TV ratio. The plasma T3 level was lower in the LA-NOX group than in the HA-OX and HA-NOX groups and T4 levels were higher in the HA-OX than in the others at 42 days old. The hypoxic conditions that occurred during the embryonic stage . which altered endogenous functions of prenatal chicks and affected several blood parameters, and oxygen supplementation at high altitude . improved chick quality. However, it did not improve subsequent FCR and feed consumption performance of chickens when they were reared at low altitude. Keywords : Breeder eggs, growth, high altitude, oxygen supplementation
A recoil resilient lumen support, design, fabrication and mechanical evaluation

Stents are artificial implants that provide scaffolding to a cavity inside the body. This paper presents a new luminal device for reducing the mechanical failure of stents due to recoil, which is one of the most important issues in stenting. This device, which we call a recoil-resilient ring (RRR), is utilized standalone or potentially integrated with existing stents to address the problem of recoil. The proposed structure aims to minimize the need for high-pressure overexpansion that can induce intra-luminal trauma and excess growth of vascular tissue causing later restenosis. The RRR is an overlapped open ring with asymmetrical sawtooth structures that are intermeshed. These teeth can slide on top of each other, while the ring is radially expanded, but interlock step-by-step so as to keep the final expanded state against compressional forces that normally cause recoil. The RRRs thus deliver balloon expandability and, when integrated with a stent, bring both radial rigidity and longitudinal flexibility to the stent. The design of the RRR is investigated through finite element analysis (FEA), and then the devices are fabricated using micro-electro-discharge machining of 200-µm-thick Nitinol sheet. The standalone RRR is balloon expandable in vitro by 5–7 Atm in pressure, which is well within the recommended in vivo pressure ranges for stenting procedures. FEA compression tests indicate 13× less reduction of the cross-sectional area of the RRR compared with a typical stainless steel stent. These results also show perfect elastic recovery of the RRR after removal of the pressure compared to the remaining plastic deformations of the stainless steel stent. On the other hand, experimental loading tests show that the fabricated RRRs have 2.8× radial stiffness compared to a two-column section of a commercial stent while exhibiting comparable elastic recovery. Furthermore, testing of in vitro expansion in a mock artery tube shows around 2.9% recoil, approximately 5–11× smaller than the recoil reported for commercial stents. These experimental results demonstrate the effectiveness of the device design for the targeted luminal support and stenting applications.