Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering host cell lines to reduce terminal sialylation of secreted antibodies

Covalently-linked glycans on proteins have many functional roles, some of which are still not completely understood. Antibodies have a very specific glycan modification in the Fc region that is required for mediating immune effector functions. These Fc glycans are typically highly heterogeneous in structure, and this heterogeneity is influenced by many factors, such as type of cellular host and rate of Ab secretion. Glycan heterogeneity can affect the Fc-dependent activities of antibodies. It has been shown recently that increased Fc sialylation can result in decreased binding to immobilized antigens and some Fcγ receptors, as well as decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activity. In contrast, increased Fc sialylation enhances the anti-inflammatory activity of antibodies. To produce antibodies with increased effector functions, we developed host cell lines that would limit the degree of sialylation of recombinantly-expressed antibodies. Towards this end, the catalytic domain of the Arthrobacter ureafaciens sialidase (sialidase A) was engineered for secreted expression in mammalian cell lines. Expression of this sialidase A gene in mammalian cells resulted in secreted expression of soluble enzyme that was capable of removing sialic acid from antibodies secreted into the medium. Purified antibodies secreted from these cells were found to possess very low levels of sialylation compared with the same antibodies purified from unmodified host cells. The low sialylated antibodies exhibited similar binding affinity to soluble antigens, improved ADCC activity, and they possessed pharmacokinetic properties comparable to their more sialylated counterparts. Further, it was observed that the amount of sialidase A expressed was sufficient to thoroughly remove sialic acid from Abs made in high-producing cell lines. Thus, engineering host cells to express sialidase A enzyme can be used to produce recombinant antibodies with very low levels of sialylation.
Patient Specific Factors Influencing Adherence to INR Monitoring

The specific reasons underlying nonadherence to monitoring the international normalized ratio (INR) from the patient's perspective have not been formally studied. Understanding why patients do or do not adhere has the potential to reveal useful targets for improving adherence to INR monitoring or alternative treatment strategies. The objective of this study was to gain further insight into INR monitoring nonadherence from the patient's perspective.
Sequential importance sampling for nonparametric Bayes models: The next generation

There are two generations of Gibbs sampling methods for semiparametric models involving the Dirichlet process. The first generation suffered from a severe drawback: the locations of the clusters, or groups of parameters, could essentially become fixed, moving only rarely. Two strategies that have been proposed to create the second generation of Gibbs samplers are integration and appending a second stage to the Gibbs sampler wherein the cluster locations are moved. We show that these same strategies are easily implemented for the sequential importance sampler, and that the first strategy dramatically improves results. As in the case of Gibbs sampling, these strategies are applicable to a much wider class of models. They are shown to provide more uniform importance sampling weights and lead to additional Rao‐Blackwellization of estimators.
Managing multi-configuration hardware via dynamic working set analysis

Microprocessors are designed to provide good average performance over a variety of workloads. This can lead to inefficiencies both in power and performance for individual programs and during individual phases within the same program. Microarchitectures with multiconfiguration units (e.g. caches, predictors, instruction windows) are able to adapt dynamically to program behavior and enable/disable resources as needed. A key element of existing configuration algorithms is adjusting to program phase changes. This is typically done by "tuning" when a phase change is detected - i.e. sequencing through a series of trial configurations and selecting the best. Algorithms that dynamically collect and analyze program working set information are studied. To make this practical, we propose working. set signatures - highly compressed working set representations (e.g. 32-128 bytes total). Algorithms use working set signatures to 1) detect working set changes and trigger re-tuning; 2) identify recurring working sets and re-install saved optimal reconfigurations, thus avoiding the time-consuming tuning process; 3) estimate working set sizes to configure caches directly to the proper size, also avoiding the tuning process. Multi-configuration instruction caches are used to demonstrate the performance of the proposed algorithms. When applied to reconfigurable instruction caches, an algorithm that identifies recurring phases achieves power savings and performance similar to the best algorithm reported to date, but with orders-of-magnitude savings in the number of re-tunings.
Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting

Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine receptor agonist, would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects, and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We examined the effects of fenoldopam on haemodynamic parameters, creatinine clearance, fractional excretion of sodium, urine output, free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation. Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1 µg. kg−1.min−1 (n = 16) or placebo (n = 15). Renal parameters were measured: during a 24‐h period before hospital admission, during cardiopulmonary bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass. Gastric intramucosal pH was measured using a gastric tonometer before, during and after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group, mean (SD) creatinine clearance decreased after separation from cardiopulmonary bypass, from 107 (36) to 71 (22) ml.min−1 (p < 0.01) and from 107 (36) to 79 (26) ml.min−1 (p < 0.01) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in both groups. The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.
Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression

Significance High-risk neuroblastoma remains a therapeutic challenge, and adjuvant retinoic acid (RA) treatment shows poor efficacy. We demonstrate that combined treatment with 5-Aza-deoxycytidine (AZA) and RA impedes neuroblastoma growth and induces a transcriptional response characterized by high levels of the HIF2α transcription factor. This approach targets high-risk neuroblastoma that responds poorly to RA. In addition, genome-wide analysis of treated tumors and patient data links HIF2α to tumor suppression, which is supported by a HIF2α-specific small molecule inhibitor-mediated block of the tumor response to AZA+RA treatment. Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors. Combining the reversibility of DNA methylation with the differentiation-promoting activity of retinoic acid (RA) could provide an alternative strategy to treat high-risk neuroblastoma. Here we show that treatment with the DNA-demethylating drug 5-Aza-deoxycytidine (AZA) restores high-risk neuroblastoma sensitivity to RA. Combined systemic distribution of AZA and RA impedes tumor growth and prolongs survival. Genome-wide analysis of treated tumors reveals that this combined treatment rapidly induces a HIF2α-associated hypoxia-like transcriptional response followed by an increase in neuronal gene expression and a decrease in cell-cycle gene expression. A small-molecule inhibitor of HIF2α activity diminishes the tumor response to AZA+RA treatment, indicating that the increase in HIF2α levels is a key component in tumor response to AZA+RA. The link between increased HIF2α levels and inhibited tumor growth is reflected in large neuroblastoma patient datasets. Therein, high levels of HIF2α, but not HIF1α, significantly correlate with expression of neuronal differentiation genes and better prognosis but negatively correlate with key features of high-risk tumors, such as MYCN amplification. Thus, contrary to previous studies, our findings indicate an unanticipated tumor-suppressive role for HIF2α in neuroblastoma.
Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride (CoCl2) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury in neonatal rat brain. We examined long-term functional and protective actions of preconditioning induced by hypoxia, CoCl2 and DFX in a neonatal rat model of HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8% oxygen) or injections of CoCl2, DFX or saline vehicle and 24 h later rats underwent HI or sham surgery. Behavioral tests were performed and at the conclusion of experiments, brains removed for morphologic analyses. HI resulted in a large unilateral lesion in the ipsilateral hemisphere compared with sham control rats. All preconditioning treatments significantly reduced the total lesion volume. Behavioral deficits were observed in HI rats compared with sham controls. The reduction in forelimb grasping strength in HI rats was attenuated by preconditioning with hypoxia, CoCl2 and DFX. HI increased the number of foot faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder test. Only preconditioning with hypoxia reversed all three functional deficits after HI. These findings indicate that preconditioning, especially when induced by hypoxia, has the potential to minimize the morphologic and functional effects of neonatal HI injury.
Smoking outcome expectancies mediate the association between sensation seeking, peer smoking, and smoking among young adolescents.

BACKGROUND Sensation seeking is a strong correlate of smoking among adolescents, yet the research on mediators of this association is not well established. The proposed model of the present study includes antecedent variables (sensation seeking), mediators (perceived peer smoking, outcome expectancies including negative consequences, positive reinforcement, negative reinforcement, and appetite-and-weight control), and one outcome variable (smoking cigarettes during the past 30 days). METHODS Self-reported data obtained from Hungarian high-school students (ninth grade, N = 2,565, mean age 15.3 years, SD = 0.56) were analyzed with structural equation modeling. Before testing of the main model, the construct validity of mediators (outcome expectancy scales) was supported with confirmatory factor analysis (CFA) and structural equation modeling. The final model was tested with structural equation modeling, and the goodness-of-fit indices and the proportion of direct and indirect effects were analyzed. RESULTS Our mediational model had an excellent model fit, and this study supported both the proposed sensation seeking-->positive and negative reinforcement-->smoking behavior pathways and sensation seeking-->perceived peer smoking-->positive and negative reinforcement-->smoking behavior pathways. The total indirect effect explains 76% of sensation seeking and smoking association. Results support the notion that positive and negative reinforcement expectancies mediate between sensation seeking and smoking. DISCUSSION Results support the notion that perceived peer smoking, positive and negative reinforcement expectancies mediate between sensation seeking and smoking.
eShiver: Lateral Force Feedback on Fingertips through Oscillatory Motion of an Electroadhesive Surface

We describe a new haptic force feedback device capable of creating lateral shear force on a bare fingertip—the eShiver. The eShiver creates a net lateral force from in-plane oscillatory motion of a surface synchronized with a “friction switch” based on Johnsen-Rahbek electroadhesion. Using an artificial finger, a maximum net lateral force of <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math><alternatives> <inline-graphic xlink:href="mullenbach-ieq1-2630057.gif"/></alternatives></inline-formula>300 mN is achieved at 55 Hz lateral oscillation frequency, and net force is shown to be a function of velocity and applied voltage, as well as the phase between them. A second set of experiments is carried out on a human finger, and a lateral force of up to <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math><alternatives> <inline-graphic xlink:href="mullenbach-ieq2-2630057.gif"/></alternatives></inline-formula>450 mN is achieved at a lateral oscillation frequency of 1,000 Hz. This force is reached at a peak lateral surface velocity of 400 mm/s and a peak applied voltage of 400 V. We develop a simple lumped parameter model of the eShiver, and a time domain simulation of the artificial finger is shown to agree with the experimental results. Three distinct zones of operation are found, which predict the limitations of force generation and which may be used for optimization. The human finger is found to be similar to the artificial finger in its dependence on actuation parameters, suggesting that the same lumped parameter model may be applied, albeit with different parameters. Curiously, the friction force due to Johnsen-Rahbek electroadhesion is found to increase substantially over time as the finger remains in contact with the surface. Considerations for optimizing the performance of the eShiver are discussed.
Citizen-centered e-government services: benefits, costs, and research needs

The promise of E-Government (and its more recent spin-offs of E-Democracy, E-Participation, E-Procurement, and a range of other "E-'s") is to engage citizenry in government in a user-centered manner, but also to develop quality government services and delivery systems that are efficient and effective. User-centered E-Government suggests that governments will provide services and resources tailored to the actual service and resource needs of users, including citizens, residents, government employees, and others. Efficient and effective E-Government suggests that governments will gain economies of scale, reduce costs, and provide technology-enabled user services. The extent to which these goals of E-Government are mutually exclusive is an issue that requires additional study, particularly research that focuses on the relationship between citizen-centered E-Government services and the attainment of cost savings. A key issue is that citizencentered E-Government implies that governments know what citizens want from E-Government, want to meet citizen expectations and needs, and actively seek to discover what citizens want from E-Government. This paper presents a range of issues associated with the development and implementation of citizen-centered e-Government.
The Antecedents of Creativity Revisited: A Process Perspective

This study invokes a process view on employee creativity to uncover how the different stages of the creative process are associated with different antecedents. Specifically, we explore the role of five previously identified antecedents of organizational creativity in the different phases of the creative process within organizations: (1) personality; (2) rewards; (3) the role of co-workers; (4) leadership; and (5) organizational resources. In an analysis of 22 case studies we found that antecedents of creativity indeed have different roles in different stages of the creative process and that antecedents that are helpful in one stage of the creative process, can be detrimental for another stage. Such results highlight the importance of conceptualizing creativity as a process, rather than as an outcome variable.
Environmental monitoring programme in the cell therapy facility of a research centre: preliminary investigation.

INTRODUCTION Recent discoveries in cell therapy research present new opportunities for cellular products to be used to treat severe, and as yet incurable, diseases. It is therefore essential to implement a quality control programme in order to ensure that safe cells and tissues are provided. METHODS In a preliminary phase of the setting up of a the cellfactory, monitoring was carried out monthly over a 6-month period in one out of three cell therapy laboratories and filter rooms in order to evaluate the microbial contamination of air and surfaces and the presence of airborne particulates. RESULTS The mean total bacterial and fungal loads measured in the air in the centre of the filter room were 20.7 +/1 28.9 colony-forming units (cfu)/m3 and 9.2 +/- 15.4 cfu/m3, respectively, and 5.2 +/- 4.1 cfu/m3 and 6.8 +/- 13.4 cfu/m3, respectively, in the laboratory. The mean fungal load values recorded on the surfaces sampled in the laboratory were in 6 out of 18 cases higher than the reference values (5 cfu/plate). As to the results of particulate monitoring, with regard to the 0.5 microm particles, about 83% of the samples revealed values below the limit of 350.000 particles per cubic metre. CONCLUSIONS In this set-up phase, monitoring was able to pick out structural and organisational flaws acceptable in a laboratory compliant with Good Manufacturing Practices class C (Annex 1), but not in a class B facility. Thanks to this preliminary monitoring phase, and by correcting these flaws, the clean room facility could achieve compliance to class B.
Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis.

OBJECTIVE To explore all the common clinical and biological variables that are characteristic of Systemic onset Juvenile Chronic Arthritis (SoJCA) in order to determine which of them are suitable as predictors of a bad articular outcome (persistence of inflammatory symptoms and/or established limitation of the range of motion (ROM). MATERIAL AND METHODS Clinical charts for 124 SoJCA patients were retrospectively reviewed. From them, 91 were finally included in the study because they had all of the clinical and biological data at disease onset properly recorded. All have been followed for at least 3 years since the beginning of the disease. Data collected at onset, and after 3 and 6 months of the disease included: 1) systemic symptoms; 2) joint involvement, using both the usual articular count and the value of an articular index (Helsinki Index = HI) which intentionally excludes those joints that are not uniformly recorded in clinical charts; and 3) biological data. HI was used to separate the patients into two groups. When applied 3 years after the disease onset, HI > or = 10 represented a bad articular outcome while HI < 10 meant a good prognosis. SPSS for Windows 6.1 was used for both the univariate and multivariate analyses. RESULTS From the multivariate logistic regression analysis, two different "clusters" of clinical data were found to be the best predictors of a bad articular outcome. A bad prognosis was linked at onset with the presence of generalized lymphadenopathies, age < 8 years and an HI > 6; at six months a bad outcome was linked with the presence of a polyarticular pattern plus hip involvement. CONCLUSION Clinical parameters at the beginning of the disease were shown to be extremely useful in predicting the articular outcome of SoJCA. Therefore, they could constitute a good instrument to help clinicians tailor the best therapy for their patients.
An investigation of antecedents of organizational citizenship behavior in the Turkish hospitality industry: a structural equation approach

Purpose – This paper aims to investigate the relationships between organizational citizenship behavior (OCB) and its antecedents – job satisfaction (JS), affective commitment (AC), organizational justice (OJ) and charismatic leadership (CL); the relationships among its antecedents; and mediating roles of JS and AC in the relationships between CL and OCB and between OJ and OCB in the Turkish hospitality industry in Antalya region. Improving OCB in the hospitality industry, as in other industries, plays an important role in increasing service quality and organization performance. Design/methodology/approach – The sample used for this study consisted of 768 employees working in 18 hotels (4- or 5-Star) in the Antalya region of Turkey. The data collection methodology of the study was a questionnaire survey which was administered through drop-and-collect methodology. The analysis methodology of the study was structural equation modeling. Findings – The findings indicated that both AC and JS mediated the relati.