In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Ex Input:
We previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, however, improving neurological function. The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic activity and devoid of the EPO side eff ects, but with apparently well maintained cytoprotective qualities [3]. We therefore tested the hypothesis whether cEPO may be equally effi cient as EPO in reducing morphological as well as functional aortic occlusion-induced spinal cord I/R injury. Methods In a randomized and blinded trial pigs received either vehicle (control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over 30 minutes before and during the fi rst 4 hours of reperfusion). Animals underwent 30 minutes of thoracic aortic balloon occlusion with catheters placed immediately downstream of the A. subclavia and upstream of the aortic trifurcation. Spinal cord function was assessed by motor evoked potentials (MEP as percentage of the amplitude before aortic occlusion) and lower limb refl exes (assessed as the subjective strength of response) for a period of 10 hours after reperfusion. Tissue damage was evaluated using Nissl staining. Results Both EPO-treated and cEPO-treated animals presented with attenuated spinal cord injury in the Nissl staining (median (quartile) percentage of damaged neurons in the thoracic segments: control 27 (25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001 vs control group). However, while only cEPO treatment was associated with recovery of the MEP amplitude to pre-occlusion values when compared with the control group (P <0.05), lower limb refl ex response was comparably restored stronger in both treatment groups (P <0.05 vs control). Conclusions In a clinically relevant porcine model mimicking aortic crossclamping during vascular surgery repair of thoracic aortic aneurysm, cEPO protected spinal cord function and integrity as eff ective as EPO when applied at equipotent doses. Acknowledgements Supported by the Deutsche Forschungs gemeinschaft (SCHE 899/2-2). Figure 1 (abstract P2). Phenylbutyrate reduced the unfolded protein response. Introduction In awake, spontaneously breathing mice, inhaling hydrogen sulfi de (H 2 S) induced a hibernation-like metabolic state characterised by reduced energy expenditure and hypothermia [1], which protected against otherwise lethal hypoxia [2] and hemorrhage [3] as a result of impaired cellular energy metabolism [4]. Therefore, we investigated the metabolic eff ects of inhaled H 2 S in our model of resuscitated murine septic shock. Methods Sixteen hours after induction of sepsis by cecal ligation and puncture (CLP) or sham operation, anesthetized and mechanically ventilated mice received 100 ppm H 2 S or vehicle over 5 hours at body temperatures of 38 and 27°C, respectively. During the observation period, hyperdynamic hemodynamics were maintained by colloid resuscitation and noradrenaline infusion [5]. Endogenous glucose production was calculated from blood 13 C6-glucose isotope enrichment derived from the rate of appearance of stable, non-radioactive labeled 1,2,3,4,5,6-13 C6 glucose during continuous isotope infusion [6]. Whole-body glucose oxidation rate was derived from the total CO 2 -production rate, the mixed expiratory 13 CO 2 / 12 CO 2 isotope ratio and the 13 C6-glucose infusion rate after the steady state was achieved. Results While endogenous glucose production was not aff ected by hypothermia, it was signifi cantly higher in the septic animals when compared with the corresponding sham operated groups, most likely due to the ongoing noradrenaline infusion. In contrast, despite the catecholamine infusion and higher glucose release, whole body glucose oxidation was signifi cantly reduced in normothermic septic animals. During hypothermia, H 2 S shifted substrate towards preferential glucose utilisation, but this eff ect disappeared in the septic mice. Conclusions H 2 S inhalation alone does not infl uence glucose metabolism once temperature is maintained at normothermic levels in anesthetised and mechanically ventilated mice. The H 2 S-related shift of energy metabo lism towards preferential carbohydrate oxidation present during hypothermia is blunted during sepsis, possibly as a result of the ongoing catecholamine treatment.

Ex Output:
P1 Comparison of carbamylated versus recombinant erythropoietin during spinal cord ischemia/reperfusion injury P2 Sodium 4-phenylbutylate protects against myocardial ischemia-reperfusion injury by reducing unfolded protein response-mediated apoptosis in mice P3 Time-dependent eff ects of intravenous H 2 S during long-term, resuscitated porcine hemorrhagic shock


Ex Input:
Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratoryconfirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.

Ex Output:
Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015


Ex Input:
Extensive functional studies of the exchange protein directly activated by cAMP (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a fundamental role in several physiological and pathophysiological responses, therefore are attractive drug targets. In this report, the development of a cell-based, medium to high throughput screening assay that is capable of monitoring EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is described. This assay adapts a conventional ELISA format with immobilized RalGDS-RBD as a bait to selectively capture GTP-bound active Rap1. As a result, it fills an urgent need for a cell-based EPAC assay that can be conveniently performed using microtiter plates for the discovery and/or validation of isoform-specific EPAC agonists and antagonists. Exchange proteins directly activated by cAMP (EAPC1 and EPAC2) mediate the intracellular functions of cAMP by acting as guanine nucleotide exchange factors for the Ras-like small GTPases, Rap1 and Rap2 1, 2 . Extensive studies have demonstrated that EPAC proteins are important signaling molecules involved in modulating a myriad of physiological functions 3-5 , ranging from energy homeostasis 6-8 and insulin secretion 9, 10 to learning and memory 11, 12 . In addition, EPAC proteins have also been shown to act as major stress-response mediators and play key roles in the development of human diseases, such as cancer 13-16 , chronic pain 17-19 , cardiovascular diseases 20, 21 and infection 22, 23 . Therefore, developing small molecule EPAC-specific modulators has evolved into an active area of research within the field for the last few years [24] [25] [26] . Several recent studies have reported the effective development of EPAC-specific antagonists using high throughput screening (HTS) biochemical assays 27-29 . However, a robust cell-based assay equipped to measure the activity of EPAC proteins in a medium to high throughput setup is lacking. In this study, the design and execution of an isoform specific cell-based assay capable of measuring cellular activity of EPAC proteins in a microplate format are described. Assay design. To develop a cell-based, isoform-specific EPAC activation assay, HEK293 cell lines stably expressing Flag-tagged Rap1A and full-length EPAC1 or EPAC2 are proposed. HEK293 cells express minimal endogenous levels of EPAC1 and EPAC2 and have been used as host cells for evaluating the cellular activities of ectopically expressed EPAC proteins in an isoform-specific manner 28 . Activation of EPAC1 or EPAC2 in these cell lines by cAMP elevating agents leads to the accumulation of Flag-Rap1-GTP, which can be captured by RalGDS-RBD immobilized in a nickel-coated 96-well microplate. The levels of active Flag-Rap1-GTP protein can be quantitatively monitored using a specific anti-FLAG antibody and a HRP conjugated secondary antibody in a manner similar to that of a conventional ELISA assay (Fig. 1) . Rap-GTP levels, which would decrease signal-to-noise ratio and dynamic range of our proposed assay. To optimize the assay, individual stable clones of HEK293/hEPAC1/Flag-Rap1 or HEK293/mEPAC2/ Flag-Rap1 were first established and tested for their basal Rap1-GTP activates. Overall, HEK293/mEPAC2/ Flag-Rap1 cells had higher basal Rap1-GTP activates than their hEPAC1 counterparts, and the basal activities varied within a range of 3-fold among different stable clones. Stable clones with lowest basal activity for HEK293/hEPAC1/ Flag-Rap1 or HEK293/mEPAC2/ Flag-Rap1 were selected, expanded and used for subsequent studies. After

Ex Output:

A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP OPEN