Miracle-dz/UniFAR-FTUs huggingface dataset:
Double Blockade of CD14 and Complement C5 Abolishes the Cytokine Storm and Improves Morbidity and Survival in Polymicrobial Sepsis in Mice

Sepsis and septic shock, caused by an excessive systemic host-inflammatory response, are associated with high morbidity and mortality. The complement system and TLRs provide important pattern recognition receptors initiating the cytokine storm by extensive cross-talk. We hypothesized that double blockade of complement C5 and the TLR coreceptor CD14 could improve survival of experimental polymicrobial sepsis. Mice undergoing cecal ligation and puncture (CLP)–induced sepsis were treated with neutralizing anti-CD14 Ab biG 53, complement C5 inhibitor coversin (Ornithodoros moubata C inhibitor), or a combination thereof. The inflammatory study (24-h observation) revealed statistically significant increases in 22 of 24 measured plasma biomarkers in the untreated CLP group, comprising 14 pro- and anti-inflammatory cytokines and 8 chemokines, growth factors, and granulocyte activation markers. Single CD14 or C5 blockade significantly inhibited 20 and 19 of the 22 biomarkers, respectively. Combined CD14 and C5 inhibition significantly reduced all 22 biomarkers (mean reduction 85%; range 54–95%) compared with the untreated CLP group. Double blockade was more potent than single treatment and was required to significantly inhibit IL-6 and CXCL1. Combined inhibition significantly reduced morbidity (motility and eyelid movement) and mortality measured over 10 d. In the positive control CLP group, median survival was 36 h (range 24–48 h). Combined treatment increased median survival to 96 h (range 24–240 h) (p = 0.001), whereas survival in the single-treatment groups was not significantly increased (median and range for anti-CD14 and anti-C5 treatment were 36 h [24–48 h] and 48 h [24–96 h]). Combined with standard intervention therapy, specific blockade of CD14 and C5 might represent a promising new therapeutic strategy for treatment of polymicrobial sepsis.
Atropine improves insulin sensitivity in both lean and abdominally obese subjects.

BACKGROUND Dysregulated autonomic nerve activity may contribute to the development of type 2 diabetes. The aim of this study was to assess the effects of an anticholinergic agent, atropine, and a cholinergic agent, physostigmine, on insulin sensitivity in lean and abdominally obese subjects. SUBJECTS AND METHODS In a single-blinded three-way crossover study, six lean and six abdominally obese nondiabetic subjects [three males and three females in each group; age, 43.8 ± 14.8 vs. 46.8 ± 4.8 yr (mean ± sd); body mass index, 22.6 ± 1.7 vs. 28.8 ± 1.3 kg/m(2); and waist circumference, 85 ± 2 vs. 99 ± 6 cm, respectively] were given iv infusions with atropine (15 μg/kg bolus, 4 μg/kg · h infusion), physostigmine (0.12 μg/kg · min) or saline (0.9% NaCl) in a randomized treatment order. Infusions were started 30 min before and continued throughout a 120-min euglycemic (5.6 mm) hyperinsulinemic (40 mU/m(2) · min) clamp. RESULTS Insulin sensitivity (M-value, i.e. glucose infusion rate divided by lean body mass) during the last 60 min of the clamp was higher during infusion with atropine than saline (9.2 ± 1.0 vs. 7.6 ± 1.0 mg/kg lean body mass · min, mean ± sem; P = 0.015) in all subjects. Physostigmine did not differ significantly from saline (8.2 ± 1.0). M-values were significantly higher in lean vs. obese [atropine, 11.6 ± 1.4 vs. 7.6 ± 1.3; physostigmine, 10.8 ± 1.3 vs. 6.3 ± 1.3; and saline, 9.1 ± 1.4 vs. 6.4 ± 1.3, respectively (all P < 0.05)], but the incremental effect of atropine vs. saline did not differ consistently between groups. CONCLUSION Insulin sensitivity was higher during a short-term atropine infusion compared with saline in both lean and abdominally obese subjects. This insulin-sensitizing effect of cholinergic blockade is unexpected, and the underlying mechanisms should be further investigated.
EXPERIMENTS ON THE STABILITY OF SPIRAL FLOW BETWEEN ROTATING CYLINDERS.

If we now remember that B is a characteristic of the field of turbulence and that Xij varies with the square of the linear scale, we see that Dij varies as the 4/3 power of the linear scale, which is Richardson's law. Notice that (5.9) predicts the same ratio between all the components of Xij and those of Xij = 2Dip. Thus, the results obtained here can be subjected to a more detailed observational test.
Consequences of Fas-Mediated Human Dendritic Cell Apoptosis Induced by Measles Virus

ABSTRACT Mortality from measles virus (MV) infection is caused mostly by secondary infections associated with a pronounced immunosuppression. Dendritic cells (DCs) represent a major target of MV and could be involved in immunosuppression. In this study, human monocyte-derived DCs were used to demonstrate that DC apoptosis in MV-infected DC–T-cell cocultures is Fas mediated, whereas apoptotic T cells could not be rescued by blocking the Fas pathway. Two novel consequences of DC apoptosis after MV infection were demonstrated. (i) Fas-mediated apoptosis of DCs facilitates MV release, while CD40 activation enhances MV replication in DCs. Indeed, detailed studies of infectious MV release and intracellular MV nucleoprotein (NP) showed that inhibition of CD40-CD40L ligand interaction blocks NP synthesis. We conclude that the CD40 ligand expressed by activated T cells first enhances MV replication in DCs, and then Fas ligand produced by activated T cells induces Fas-mediated apoptosis of DCs, thus facilitating MV release. (ii) Not only MV-infected DCs but also bystander uninfected DCs undergo a maturation process confirmed by CD1a, CD40, CD80, CD86, CD83, and major histocompatibility complex type II labeling. The bystander maturation effect results from contact and/or engulfment of MV-induced apoptotic DCs by uninfected DCs. A model is proposed to explain how both a specific immune response and immunosuppression can simultaneously occur after MV infection through Fas-mediated apoptosis and CD40 activation of DCs.
Toll-like Receptors and Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is one relapsing and lifelong disease that affects millions of patients worldwide. Increasing evidence has recently highlighted immune-system dysfunction, especially toll-like receptors (TLRs)-mediated innate immune dysfunction, as central players in the pathogenesis of IBD. TLRs and TLR-activated signaling pathways are involved not only in the pathogenesis but also in the efficacy of treatment of IBD. By understanding these molecular mechanisms, we might develop a strategy for relieving the experience of long-lasting suffering of those patients and improving their quality of life. The purpose of this review article is to summarize the potential mechanisms of TLR signaling pathways in IBD and the novel potential therapeutic strategies against IBD.
Triterpenoids from the Herbs of Salicornia bigelovii

A new nortriterpene saponin, 3-O-β-d-glucuronopyranosyl-30-norolean-12,20(29)-dien-23-oxo-28-oic acid, namely bigelovii D (11), was isolated from the hydroalcoholic extract of herbs of Salicornia bigelovii along with 10 known saponins (1–10). Their chemical structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and a comparison with literature data. Some of these compounds showed potent antifungal activities in vitro. Compounds 3, 4, 5, 6, 7, 10 and 11 demonstrated potent inhibitory activities against Colletotrichum gloeosporioides and compound 11 displayed broad-spectrum inhibitory activity against Alternaria alternata, A. solani, Botrytis cinerea, C. gloeosporioides, Fusarium graminearum, F. verticilloides, Thanatephorus cucumeris and Sclerotinia sclerotiorum, with EC50 values ranging from 13.6 to 36.3 μg/mL.
Status review report : great hammerhead shark (Sphyrna mokarran)

ii ACKNOWLEDGEMENTS The National Marine Fisheries Service (NMFS) gratefully acknowledges the commitment and efforts of the Extinction Risk Analysis (ERA) team members and thanks them for generously contributing their time and expertise to the development of this status review report. Numerous individual fishery scientists and managers provided information that aided in preparation of this report and deserve special thanks. We particularly wish to thank Ms. for information, data, and professional opinions. We would also like to thank those who submitted information through the public comment process. We would especially like to thank the peer reviewers Dr. Freddy Arocha, Mr. Mika Diop, and Dr. Yannis Papastamatiou for their time and professional review of this report. iii EXECUTIVE SUMMARY This status review report was conducted in response to two petitions to list the great hammerhead NMFS evaluated the petitions to determine whether the petitioners provided substantial information as required by the ESA to list a species. Additionally, NMFS evaluated whether information contained in the petitions might support the identification of a distinct population segment (DPS) that may warrant listing as a species under the ESA. NMFS determined that the petitions presented substantial scientific and commercial information, or cited such information in other sources, that the petitioned action may be warranted and, subsequently, NMFS initiated a status review of the great hammerhead shark. This status review report is comprised of two components: (1) the " Status Review " of the species, a document that compiles the best available information on the status of the great hammerhead shark as required by the ESA, and (2) the " Assessment of Extinction Risk " for the species, a document that provides the methods and conclusions of the NMFS Extinction Risk Analysis (ERA) team on the current and future extinction risk of the great hammerhead shark. The great hammerhead shark (Sphyrna mokarran) is a circumtropical species that lives in coastal-pelagic and semi-oceanic waters. It occurs over continental shelves as well as adjacent deep waters, and may also be found in coral reefs and lagoons (Compagno 1984; Denham et al. 2007; Bester n.d.). Female great hammerhead sharks are viviparous (i.e., give birth to live young) and breed only once every two years (Stevens and Lyle 1989). Litter sizes range from 6 to 42 pups. Overall, great hammerhead shark exhibit life-history traits and population parameters that are intermediary among other shark species. Unlike scalloped hammerhead sharks, great hammerheads are …
An Empirical Study of the Domain Dependence of Supervised Word Sense Disambiguation Systems

This paper describes a set of experiments carried out to explore the domain dependence of alternative supervised Word Sense Disambiguation algorithms. The aim of the work is threefold: studying the performance of these algorithms when tested on a different corpus from that they were trained on; exploring their ability to tune to new domains, and demonstrating empirically that the LazyBoosting algorithm outperforms state-of-theart supervised WSD algorithms in both previous situations.
Methods to Transfer Foreign Genes to Plants

Genome sequencing of several organisms has resulted in the rapid progress of genomic studies. Genetic transformation is a powerful tool and an important technique for the study of plant functional genomics, i.e., gene discovery, new insights into gene function, and investigation of genetically controlled characteristics. In addition, the function of genes isolated using map-based cloning of mutant alleles has been confirmed by functional complementation using genetic transformation. Furthermore, genetic transformation enables the introduction of foreign genes into crop plants, expeditiously creating new genetically modified organisms. Gene transformation and genetic engineering contribute to an overall increase in crop productivity (Sinclair et al., 2004).
Conditional, Genetically Encoded, Small Molecule–Regulated Inhibition of NFκB Signaling in RPE Cells

Purpose Nuclear factor κB (NFκB) is a ubiquitously expressed, proinflammatory transcription factor that controls the expression of genes involved in cell survival, angiogenesis, complement activation, and inflammation. Studies have implicated NFκB-dependent cytokines or complement-related factors as being detrimentally involved in retinal diseases, thus making inhibition of NFκB signaling a potential therapeutic target. We sought to develop a conditional and reversible method that could regulate pathogenic NFκB signaling by the addition of a small molecule. Methods We developed a genetically based, trimethoprim (TMP)-regulated approach that conditionally inhibits NFκB signaling by fusing a destabilized dihydrofolate reductase (DHFR) domain to an inhibitor of NFκB, IκBα, in ARPE-19 cells. We then challenged ARPE-19 cells with a number of stimuli that have been demonstrated to trigger NFκB signaling, including LPS, TNFα, IL-1α, and A2E. Western blotting, electrophoretic mobility shift assay, quantitative PCR, ELISA, and NFκB reporter assays were used to evaluate the effectiveness of this DHFR-IκBα approach. Results This destabilized domain approach, coupled with doxycycline-inducibility, allowed for accurate control over the abundance of DHFR-IκBα. Stabilization of DHFR-IκBα with TMP prevented IL-1α-, A2E-, LPS-, and TNFα-induced NFκB-mediated upregulation and release of the proinflammatory cytokines IL-1β and IL-6 from ARPE-19 cells (by as much as 93%). This strategy is dosable, completely reversible, and can be cycled “on” or “off” within the same cell population repeatedly to confer protection at desired time points. Conclusions These studies lay the groundwork for the use of destabilized domains in retinal pigment epithelium (RPE) cells in vivo and in this context, demonstrate their utility for preventing inflammatory signaling.
A comparison of intravascular and surface cooling techniques in comatose cardiac arrest survivors*

Objectives:Mild therapeutic hypothermia after out-of-hospital cardiac arrest is usually achieved either by surface cooling or by core cooling via the patient's bloodstream. We compared modern core (Coolgard) and surface (Arctic Sun) cooling devices with a zero hypothesis of equal cooling, complications, and neurologic outcomes. Design:Single-center observational study. Setting:University hospital medical and cardiac intensive care units. Patients:One hundred sixty-seven consecutive patients comatose after out-of-hospital cardiac arrest of all causes treated with mild therapeutic hypothermia in a 5-yr period. Interventions:Nonrandomized allocation to core or surface cooling depending on availability and physician preference. Measurements and Main Results:All out-of-hospital cardiac arrest patients' records were reviewed for relevant data regarding medical history, cardiac arrest event, prehospital care, in-hospital treatment, and complications. Survivor neurologic function was reassessed at follow-up after 6 to 12 months. Baseline patient and arrest episode characteristics were similar in the treatment groups. There was no significant difference in survival with good neurologic function, either to hospital discharge (surface, 34/90, 38%; core, 34/75, 45%; p = .345) or at follow-up (surface, 34/88, 39%; core, 34/75, 45%; p = .387). Time from cardiac arrest to achieving mild therapeutic hypothermia was equal with both devices (surface, 273 min, interquartile range 158–330; core, 270 min, interquartile range 190–360; p = .479). There were significantly more episodes of sustained hyperglycemia among the surface-cooled patients (surface, 64/92, 70%; core, 36/75, 48%; p = .005) and significantly more hypomagnesaemia among core-cooled patients (surface, 16/87, 18%; core, 27/74, 37%; p = .01). Conclusions:In this study, surface and core cooling of out-of-hospital cardiac arrest patients following the same established postresuscitation treatment protocol resulted in similar survival to hospital discharge and comparable neurologic function at follow-up.
Growth of the Decision Tree: Advances in Bottom‐Up Climate Change Risk Management

There has recently been a return in climate change risk management practice to bottom‐up, robustness‐based planning paradigms introduced 40 years ago. The World Bank's decision tree framework (DTF) for “confronting climate uncertainty” is one incarnation of those paradigms. In order to better represent the state of the art in climate change risk assessment and evaluation techniques, this paper proposes: (1) an update to the DTF, replacing its “climate change stress test” with a multidimensional stress test; and (2) the addition of a Bayesian network framework that represents joint probabilistic behavior of uncertain parameters as sensitivity factors to aid in the weighting of scenarios of concern (the combination of conditions under which a water system fails to meet its performance targets). Using the updated DTF, water system planners and project managers would be better able to understand the relative magnitudes of the varied risks they face, and target investments in adaptation measures to best reduce their vulnerabilities to change. Next steps for the DTF include enhancements in: modeling of extreme event risks; coupling of human‐hydrologic systems; integration of surface water and groundwater systems; the generation of tradeoffs between economic, social, and ecological factors; incorporation of water quality considerations; and interactive data visualization.
The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics

The Carbohydrate-Active Enzyme (CAZy) database is a knowledge-based resource specialized in the enzymes that build and breakdown complex carbohydrates and glycoconjugates. As of September 2008, the database describes the present knowledge on 113 glycoside hydrolase, 91 glycosyltransferase, 19 polysaccharide lyase, 15 carbohydrate esterase and 52 carbohydrate-binding module families. These families are created based on experimentally characterized proteins and are populated by sequences from public databases with significant similarity. Protein biochemical information is continuously curated based on the available literature and structural information. Over 6400 proteins have assigned EC numbers and 700 proteins have a PDB structure. The classification (i) reflects the structural features of these enzymes better than their sole substrate specificity, (ii) helps to reveal the evolutionary relationships between these enzymes and (iii) provides a convenient framework to understand mechanistic properties. This resource has been available for over 10 years to the scientific community, contributing to information dissemination and providing a transversal nomenclature to glycobiologists. More recently, this resource has been used to improve the quality of functional predictions of a number genome projects by providing expert annotation. The CAZy resource resides at URL: http://www.cazy. org/.
Trinitrophenyl modification of H-2k and H-2b spleen cells results in enhanced serological detection of Kk-like determinants

Several anti-H-2Kk but not anti-H-2Dd monoclonal antibodies (mAb) exhibited enhanced binding to B10.A murine spleen cells after modification of the cells with trinitrobenzene sulfonate (TNBS). The number of antibody molecules bound to TNP-modified B10.A spleen cells increased by a factor of two or more. The same anti-2Kk mAb that exhibited enhanced binding to modified B10.A cells did not bind to unmodified C57BL/10 spleen cells, as expected, but did bind to TNP- modified C57BL/10 spleen cells. This TNP-dependent binding was not a result of cross-reactions with cell surface TNP groups nor with Fc receptors. TNP modification of a variant cell line that does not express class I H-2 products did not result in enhanced binding by these mAb. These findings can account for preferential recognition of TNP-Kk by B10.A and B10.BR CTL, and also for cross-reactive lysis by C57BL/10 CTL stimulated by C57BL/10-TNP against unmodified H-2Kk targets.
The Youth Physical Development Model: A New Approach to Long-Term Athletic Development

SUMMARY THE DEVELOPMENT OF PHYSICAL FITNESS IN YOUNG ATHLETES IS A RAPIDLY EXPANDING FIELD OF INTEREST FOR STRENGTH AND CONDITIONING COACHES, PHYSICAL EDUCATORS, SPORTS COACHES, AND PARENTS. PREVIOUS LONG-TERM ATHLETE DEVELOPMENT MODELS HAVE CLASSIFIED YOUTH-BASED TRAINING METHODOLOGIES IN RELATION TO CHRONOLOGIC AGE GROUPS, AN APPROACH THAT HAS DISTINCT LIMITATIONS. MORE RECENT MODELS HAVE ATTEMPTED TO BRIDGE MATURATION AND PERIODS OF TRAINABILITY FOR A LIMITED NUMBER OF FITNESS QUALITIES, ALTHOUGH SUCH MODELS APPEAR TO BE BASED ON SUBJECTIVE ANALYSIS. THE YOUTH PHYSICAL DEVELOPMENT MODEL PROVIDES A LOGICAL AND EVIDENCE-BASED APPROACH TO THE SYSTEMATIC DEVELOPMENT OF PHYSICAL PERFORMANCE IN YOUNG ATHLETES.
Association of high levels of serum antibody to staphylococcal toxic shock antigen with nasal carriage of toxic shock antigen-producing strains of Staphylococcus aureus

Forty-four asymptomatic male subjects were examined for their nasal carriage of strains of Staphylococcus aureus capable of producing staphylococcal toxic shock antigen (TSA), an exotoxin implicated in the pathogenesis of toxic shock syndrome. In addition, the levels of antibody to TSA in sera from these subjects were determined by an enzyme-linked immunosorbent assay. S. aureus was isolated from the anterior nares of 23 subjects. Of those 23 isolates of S. aureus, 9 were found to produce TSA. All individuals carrying strains of S. aureus capable of producing TSA had high to moderate levels of antibody to TSA. In contrast, those individuals carrying strains not producing TSA had levels of antibody to TSA ranging from high to nondetectable. A second examination of nasal samples from 42 of these subjects revealed that 86% of those carrying S. aureus initially still carried S. aureus after a period of 3 months; all subjects found to carry TSA-producing strains initially and that were examined a second time yielded TSA-producing strains once again.
Electroacupuncture Regulates Hippocampal Synaptic Plasticity via miR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke

MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test. T2-weighted imaging showed that the MICD rat brain lesions were located in cortex, hippocampus, corpus striatum, and thalamus regions and injured volumes were reduced after EA. Furthermore, we found that the density of dendritic spine and the number of synapses in the hippocampal CA1 pyramidal cells were obviously reduced at Day 14 after MICD. However, synaptic-dendritic loss could be rescued after EA. Moreover, the synaptic-dendritic plasticity was associated with increases of the total LIMK1 and phospho-LIMK1 levels in hippocampal CA1 region, wherein EA decreased the expression of miR-134, negatively regulating LIMK1 to enhance synaptic-dendritic plasticity. Therefore, miR-134-mediated LIMK1 was involved in EA-induced hippocampal synaptic plasticity, which served as a contributor to improving learning and memory during the recovery stage of ischemic stroke.
Internet of Things and Co-creation of Value

This paper introduces a discussion and a conceptual model on value creation considering the concept of the Internet of Things. It is proposed that value creation occurs in different layers that take advantage of the development of the Internet of Things. The three parts are based on manufacturing, supporting and co-creative behavior of things. These parts of value creation are not mutually exclusive and value creation can, and should, coexist in all these layers. Hence, for different phases in the development, firms and situations, the layers fit differently into a value creation process.