Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of a cDNA-clone encoding Nc-p43, a major Neospora caninum tachyzoite surface protein

Neospora caninum is an apicomplexan parasite of veterinary importance which invades many different cell types and tissues. N. caninum tachyzoites proliferate intracellularly by endodyogeny. Eventually the massive proliferation of tachyzoites leads to host cell lysis and the newly formed parasites are released and invade neighbouring cells. Tachyzoite cell surface molecules could serve as ligands, mediating host cell adhesion and invasion. Nc-p43 is a recently identified N. caninum tachyzoite surface protein which is functionally involved in the processes leading to host cell invasion in vitro. Affinity-purified antibodies directed against Nc-p43 were used to screen a lambda gt22A-cDNA expression library constructed from N. caninum tachyzoites. The cDNA insert of one immunoreactive clone was subcloned and expressed in E. coli as a poly-histidine fusion protein. The identity of the resulting recombinant antigen termed recNc-p43 was confirmed by immunoblotting, immunofluorescence and electron microscopy using affinity-purified antibodies. The sequence of the cDNA insert encoding recNc-p43 was determined. Analysis of the deduced amino acid sequence revealed that Nc-p43 exhibited similarity to SAG1 (p30) and SAG3 (p43), 2 major surface antigens of Toxoplasma gondii tachyzoites. These similarities were not reflected on the immunochemical level, since no cross-antigenicity between SAG1, SAG3 and Nc-p43 was observed.
Perceived fairness of and satisfaction with employee performance appraisal

Employee performance appraisal is one of the most commonly used management tools in the United States. Over 90 percent of large organizations including 75 percent of state employment systems require some type of annual performance appraisal (Seldon, Ingraham & Jacobson, 2001). Performance appraisal is one of the most widely researched areas in industrial/organizational psychology (Murphy & Cleveland, 1993). However, the traditional research agenda has done little to improve the usefulness of performance appraisal as a managerial tool. Recent research has moved away from studies of rater accuracy and psychometric measures to themes of employee reactions towards performance appraisal as indicators of system satisfaction and efficacy. Employee perception of fairness of performance appraisal has been studied as a significant factor in employee acceptance and satisfaction of performance appraisal. This study investigated employee reactions to fairness of and satisfaction with an existing performance appraisal system utilizing a hypothesized four-factor model (Greenberg, 1993) of organizational justice as the theoretical basis. The underlying hypothesis was that the conceptualized four-factor model, which differentiated between the constructs of interactional and procedural justice, would best represent the underlying factor structure of the data. Data were obtained via a survey questionnaire from 440 participants from two organizations that were part of a large public employment system. Ten multi-item scales
Key cost drivers of pharmaceutical clinical trials in the United States

Background: The increasing cost of clinical research has significant implications for public health, as it affects drug companies’ willingness to undertake clinical trials, which in turn limits patient access to novel treatments. Thus, gaining a better understanding of the key cost drivers of clinical research in the United States is important. Purpose: The study which is based on a report prepared by Eastern Research Group, Inc., for the US Department of Health and Human Services, examined different factors, such as therapeutic area, patient recruitment, administrative staff, and clinical procedure expenditures, and their contribution to pharmaceutical clinical trial costs in the United States by clinical trial phase. Methods: The study used aggregate data from three proprietary databases on clinical trial costs provided by Medidata Solutions. We evaluated per-study costs across therapeutic areas by aggregating detailed (per patient and per site) cost information. We also compared average expenditures on cost drivers with the use of weighted mean and standard deviation statistics. Results: Therapeutic area was an important determinant of clinical trial costs by phase. The average cost of a Phase 1 study conducted at a US site ranged from US$1.4 million (pain and anesthesia) to US$6.6 million (immunomodulation), including estimated site overhead and monitoring costs of the sponsoring organization. A Phase 2 study cost from US$7.0 million (cardiovascular) to US$19.6 million (hematology), whereas a Phase 3 study cost ranged from US$11.5 million (dermatology) to US$52.9 (pain and anesthesia) on average. Across all study phases and excluding estimated site overhead costs and costs for sponsors to monitor the study, the top three cost drivers of clinical trial expenditures were clinical procedure costs (15%–22% of total), administrative staff costs (11%–29% of total), and site monitoring costs (9%–14% of total). Limitations: The data were from 2004 through 2012 and were not adjusted for inflation. Additionally, the databases used represented a convenience, that is, non-probability, sample and did not allow for statistically valid estimates of cost drivers. Finally, the data were from trials funded by the global pharmaceutical and biotechnology industry only. Hence, our study findings are limited to that segment. Conclusion: Therapeutic area being studied as well as number and types of clinical procedures involved were the key drivers of direct costs in Phase 1 through Phase 3 studies. Research shows that strategies exist for reducing the price tag of some of these major direct cost components. Therefore, to increase clinical trial efficiency and reduce costs, gaining a better understanding of the key direct cost drivers is an important step.
Control of Natural Transformation in Salivarius Streptococci through Specific Degradation of σX by the MecA-ClpCP Protease Complex

ABSTRACT Competence for natural DNA transformation is a tightly controlled developmental process in streptococci. In mutans and salivarius species, the abundance of the central competence regulator σX is regulated at two levels: transcriptional, by the ComRS signaling system via the σX/ComX/SigX-inducing peptide (XIP), and posttranscriptional, by the adaptor protein MecA and its associated Clp ATPase, ClpC. In this study, we further investigated the mechanism and function of the MecA-ClpC control system in the salivarius species Streptococcus thermophilus. Using in vitro approaches, we showed that MecA specifically interacts with both σX and ClpC, suggesting the formation of a ternary σX-MecA-ClpC complex. Moreover, we demonstrated that MecA ultimately targets σX for its degradation by the ClpCP protease in an ATP-dependent manner. We also identify a short sequence (18 amino acids) in the N-terminal domain of σX as essential for the interaction with MecA and subsequent σX degradation. Finally, increased transformability of a MecA-deficient strain in the presence of subinducing XIP concentrations suggests that the MecA-ClpCP proteolytic complex acts as an additional locking device to prevent competence under inappropriate conditions. A model of the interplay between ComRS and MecA-ClpCP in the control of σX activity is proposed.
Layered assembly of chitosan nanoparticles and alginate gel for management of post-surgical pain and infection

Post-surgical pain and infections are the major complications encountered after every surgery. Despite various advances in the management of pain and surgical site infections (SSIs), it remains a formidable challenge to the surgeons and researchers. We need to develop a perfect biodegradable, biocompatible and efficacies system for management of post-surgical pain and infections. With this aim, we have developed layered assembly of chitosan nanoparticles (CNPs) sandwiched between alginate gel layer for delivery of antibiotic and Nonsteroidal anti-inflammatory agent (NSAID). It will help to combat pain and infection together. Also, due negatively charged alginate matrix the system also acts as a potential barrier for post-surgical tissue adhesion. CNPs were prepared by ionotropic gelation method using sodium tri-polyphosphate (TPP) as a cross linker. Sizes of the CNPs were in the range of 150-180nm with zeta potential of 32 ± 6.78mv. Encapsulation efficiency (EE) of CNPs loaded with antibiotic was 72.83 ± 2.13%. Layered assembly was formulated using layer-by-layer deposition of lyophilized CNPs and alginate gel. In vitro drug release was performed for 28 days using simulated body fluid (SBF). Release of antibiotic and NSAID was obtained for the period of 21 and 15 days respectively. Antibiotic significantly inhibits the growth of bacteria for longer period of time. Developed system demonstrates good viability and proliferation of L929 cells, indicating its biocompatibility. Thus, we can conclude that layered assembly of CNPs and alginate gel is a potential system to combat post-surgical pain and infection.
Instructions for use Title Stereotactic body radiotherapy using gated radiotherapy withreal-time tumor-tracking for stage I non-small cell lung cancer

Background: To clarify the clinical outcomes of two dose schedule of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) using a real-time tumor-tracking radiation therapy (RTRT) system in single institution. Methods: Using a superposition algorithm, we administered 48 Gy in 4 fractions at the isocenter in 2005–2006 and 40 Gy in 4 fractions to the 95% volume of PTV in 2007–2010 with a treatment period of 4 to 7 days. Target volume margins were fixed irrespective of the tumor amplitude. Results: In total, 109 patients (79 T1N0M0 and 30 T2N0M0). With a median follow-up period of 25 months (range, 4 to 72 months), the 5-year local control rate (LC) was 78% and the 5-year overall survival rate (OS) was 64%. Grade 2, 3, 4, and 5 radiation pneumonitis (RP) was experienced by 15 (13.8%), 3 (2.8%), 0, and 0 patients, respectively. The mean lung dose (MLD) and the volume of lung receiving 20 Gy (V20) were significantly higher in patients with RP Grade 2/3 than in those with RP Grade 0/1 (MLD p = 0.002, V20 p = 0.003). There was no correlation between larger maximum amplitude of marker movement and larger PTV (r = 0.137), MLD (r = 0.046), or V20 (r = 0.158). Conclusions: SBRT using the RTRT system achieved LC and OS comparable to other SBRT studies with very low incidence of RP, which was consistent with the small MLD and V20 irrespective of tumor amplitude. For stage I NSCLC, SBRT using RTRT was suggested to be reliable and effective, especially for patients with large amplitude of tumor movement.
Smart specialization as a strategy to develop early-stage regional innovation systems

ABSTRACT This paper discusses the role of smart specialization in catalyzing the development of early-stage regional innovation systems in less advanced regions, either by facilitating the emergence of some defining elements that were lacking or accelerating the development of others, such as: a regional knowledge base and a dynamic learning process, institutional structures, network integration mechanisms among key innovation actors, regional industrial specializations, and collective identities. The paper exemplifies this process with the case of Romania, a country where the research and innovation system is centralized at national level and regional innovation systems are in the early days. The transformations taking place in the Romanian regions within the process of implementing smart specialization, assisted by the European Commission's Joint Research Centre in the project “Targeted Support to Smart Specialization in Romania”, suggest a dynamic coagulation of institutional, financial, policy, and human factors that catalyzed the development of regional innovation systems in the country and introduced a novel approach to innovation policy.
Inference Procedures for Assessing Interobserver Agreement among Multiple Raters

Summary. We propose a new procedure for constructing inferences about a measure of interobserver agreement in studies involving a binary outcome and multiple raters. The proposed procedure, based on a chi‐square goodness‐of‐fit test as applied to the correlated binomial model (Bahadur, 1961, in Studies in Item Analysis and Prediction, 158–176), is an extension of the goodness‐of‐fit procedure developed by Donner and Eliasziw (1992, Statistics in Medicine11, 1511–1519) for the case of two raters. The new procedure is shown to provide confidence‐interval coverage levels that are close to nominal over a wide range of parameter combinations. The procedure also provides a sample‐size formula that may be used to determine the required number of subjects and raters for such studies.
Labor Productivity and Factors Affecting its Demand in Paddy Farms in KB province, Iran - TI Journals

Abstract: In addition to land and capital, labor force is considered as one of the most important factors affecting the production of agricultural products, and plays a significant and effective role in all production processes of a product. In this study, marginal productivity and average labor force have been calculated by the use of production function. Furthermore, to determine the effective factors on labor force, Tran-slog profit function was selected and estimated through Shepherd\s Lemma and iterative seemingly unrelated regression (ISUR). The results of this study showed that average and marginal productivity of labor force are 0.26 and 0.23, respectively. Labor demand elasticity calculation showed that fertilizer inputs and machinery are both considered as substitutes for labor. Furthermore, the results obtained from calculation of labor demand elasticity in terms of wage ratio, prices and the cultivation area showed that this elasticity is sensitive and elastic. In other words, change in wage ratio, price and cultivation area have positive effect on labor demand.
Intravenous fluid resuscitation: was Poiseuille right?

Aim To compare the flow rates of readily available intravenous infusion devices and to compare the effect of the addition of pressure or a needle-free intravenous connector device. Methods Several intravenous devices with different characteristics had their flow rates determined under a standard set of conditions. The flow rates were then measured with the addition of a pressure bag to the system and then with a needle-free intravenous connector device. The flow rates and change in flow rates were then analysed. Results The results showed a general agreement with Poiseuille's law. The needle-free connector slowed the rate of flow by up to 41.4% with the greatest effect on short, wide-bore devices. The addition of pressure had a greater effect on longer devices. Conclusions Short, wide cannulae should be used when rapid fluid resuscitation is required. Needle-free devices should not be used when rapid fluid resuscitation is needed.
Relaxin: A Novel Agent for the Treatment of Acute Heart Failure

Acute heart failure (AHF) is defined by a constellation of signs and symptoms that manifest when new or decompensated ventricular dysfunction is triggered by an acute precipitant such as excessive preload, afterload, or myocardial ischemia. Despite being one of the most frequent causes of hospitalization and cardiovascular mortality, little to no progress has been made over the last few decades to advance the treatment of AHF. Current mainstays of pharmacotherapy for AHF including diuretics, vasodilators, and inotropes can improve symptoms; however, no currently approved agent has been shown to provide lasting outcome benefit for patients with AHF. First discovered in pregnant women where it is known to help with growth of the cervix and assist with the maternal cardiovascular and renovascular responses to pregnancy, relaxin is an endogenous neurohormone that has novel vasoactive properties. In particular, relaxin is a potent vasodilator with a number of pleiotropic effects that may affect cardiac remodeling, making relaxin an attractive compound for use in the management of AHF. Indeed, in two randomized controlled trials, a single 48‐hour infusion of relaxin relieved symptoms of AHF with no evidence of major adverse effects. A signal of mortality benefit at 180 days was noted in both trials, prompting a third trial of relaxin powered for 180‐day mortality that is currently under way. The pharmacology that underscores the potential benefit of relaxin is discussed and insight is provided into future clinical application of this novel drug should it prove to be the first therapy capable of reducing mortality in AHF.
Nonheart-beating kidney donation: current practice and future developments.

BACKGROUND Nonheart-beating kidney donation (NHBD) is gaining acceptance as a method of donor pool expansion. However, a number of practitioners have concerns over rates of delayed graft function, acute rejection, and long-term graft survival. The ethical issues associated with NHBD are complex and may be a further disincentive. Tailored strategies for preservation, viability prediction, and immunosuppression for kidneys from this source have the potential to maximize the number of available organs. This review article presents the current practice of NHBD kidney transplantation, examines the results and draws comparisons with cadaveric kidneys, and explores some areas of potential development. METHODS A review of the current literature on NHBD kidney donation was performed. RESULTS The renewed interest in NHBD kidneys is driven by a continuing shortfall in available organs. Those centers involved in NHBD report an increase in kidney transplants of the order of 16% to 40% and there is no evidence that the financial costs are higher with NHBDs. The majority of experience comes from Maastricht category 2 NHBDs, where an estimation of warm time is possible. This is generally limited to 40 minutes. There are variations in the technique for kidney preservation prior to retrieval, but most centers use an aortic balloon catheter. Much work has looked at the ideal technique for kidney preservation prior to implantation. Evidence suggests that machine perfusion produces the best initial function rates, decreased use of adjuvant immunotherapy and fewer haemodialysis sessions than static cold storage. CONCLUSION Despite being associated with poorer initial graft function, the long-term allograft survival of NHBD kidneys does not differ from the results of transplantation from cadaveric kidneys. Further, serum creatinine levels are generally equivalent. Constant reassessment of the ethical issues is required for donation to be increased while respecting public concerns. Use of viability assessment and tailoring of immune suppression for NHBD kidneys may allow a further increase in donation from this source.
An integrated regulatory network including two positive feedback loops to modulate the activity of σE in mycobacteria

σE, one of the best characterized mycobacterial extracytoplasmic function sigma factors, is involved in virulence, surface stress response and modulation of the inflammatory response during infection. The regulation of its activity is very complex and involves transcriptional, translational and post‐translational control. Post‐translational regulation is controlled by RseA, an anti‐σ factor belonging to the zinc‐associated anti‐σ factor family. In this issue of Molecular Microbiology, Barik et al. demonstrate that RseA is a redox‐sensing protein that is able to bind σE only in reducing environment. Importantly, they describe a novel positive feedback loop responsible for σE release and activation following surface stress, due to ClpC1P2‐dependent proteolytic degradation of RseA, depending on its phosphorylation by the eukaryotic‐like Ser/Thr protein kinase PknB.
Selective activation of the prostaglandin E2 receptor subtype EP2 or EP4 leads to inhibition of platelet aggregation

Summary The effect of selective activation of platelet prostaglandin (PG) E2 receptor subtype EP2 or EP4 on platelet aggregation remains to be determined. In platelets prepared from wild-type mice (WT platelets), high concentrations of PGE2 inhibited platelet aggregation induced by U-46619, a thromboxane receptor agonist. However, there was no significant change in the inhibitory effect of PGE2 on platelets lacking EP2 (EP2 –/– platelets) and EP4 (EP4 –/– platelets) compared with the inhibitory effect on WT platelets. On the other hand, AE1–259 and AE1–329, agonists for EP2 and EP4, respectively, potently inhibited U-46619 -induced aggregation with respective IC50 values of 590 ± 14 and 100 ± 4.9 nM in WT platelets, while the inhibition was significantly blunted in EP2 –/– and EP4 –/– platelets. In human platelets, AE1–259 and AE1–329 inhibited U-46619-induced aggregation with respective IC50 values of 640 ± 16 and 2.3 ± 0.3 nM. Notably, the inhibitory potency of AE1–329 in human platelets was much higher than that in murine platelets, while such a difference was not observed in the inhibitory potency of AE1–259. AE1–329 also inhibited adenosine diphosphate-induced platelet aggregation, and the inhibition was almost completely blocked by AE3–208, an EP4 antagonist. In addition, AE1–329 increased intracellular cAMP concentrations in a concentration- and EP4-dependent manner in human platelets. These results indicate that selective activation of EP2 or EP4 can inhibit platelet aggregation and that EP4 agonists are particularly promising as novel anti-platelet agents.
End-of-life matters in chronic renal failure

Purpose of reviewThe population considered eligible for dialysis has expanded dramatically over the past 4 decades, so that a significant proportion of patients receiving renal replacement therapy are elderly, frail and infirm. These patients have an extremely limited life expectancy and suffer from significant symptom burden, similar to patients with other end-stage organ failure or cancer. As dialysis has been offered more broadly, it is now initiated earlier than in decades past, further adding to cost and patient burden. Recent findingsThe trend toward more expansive and intensive care has not been corroborated by robust data. In response, an increasing number of studies has focused on establishing reasonable limits to renal replacement therapy. Multiple authors have explored the role of conservative kidney management for high-risk dialysis patients as an alternative to dialysis, which may offer similar survival and improved quality of life in certain populations. For those who chose dialysis, deferring initiation until the patient becomes symptomatic may be a reasonable. Evidence-based symptom management guidelines for dialysis patients remain largely absent, with few proven approaches. Hospice and palliative care resources remain underutilized. SummaryFor a subset of dialysis patients, palliative care and conservative kidney management are appropriate and underutilized. Video abstracthttp://links.lww. com/COSPC/A8