Miracle-dz/UniFAR-FTUs huggingface dataset:
Interfacial Regulation of Acid Ceramidase Activity

The lysosomal degradation of ceramide is catalyzed by acid ceramidase and requires sphingolipid activator proteins (SAP) as cofactors in vivo. The aim of this study was to investigate how ceramide is hydrolyzed by acid ceramidase at the water-membrane interface in the presence of sphingolipid activator proteins in a liposomal assay system. The degradation of membrane-bound ceramide was significantly increased both in the absence and presence of SAP-D when anionic lysosomal phospholipids such as bis(monoacylglycero)phosphate, phosphatidylinositol, and dolichol phosphate were incorporated into substrate-bearing liposomes. Higher ceramide degradation rates were observed in vesicles with increased membrane curvature. Dilution assays indicated that acid ceramidase remained bound to the liposomal surface during catalysis. Not only SAP-D, but also SAP-C and SAP-A, were found to be stimulators of ceramide hydrolysis in the presence of anionic phospholipids. This finding was confirmed by cell culture studies, in which SAP-A, -C, and -D reduced the amount of ceramide storage observed in fibroblasts of a patient suffering from prosaposin deficiency. Strong protein-lipid interactions were observed for both SAP-D and acid ceramidase in surface plasmon resonance experiments. Maximum binding of SAP-D and acid ceramidase to lipid bilayers occurred at pH 4.0. Our results demonstrate that anionic, lysosomal lipids are required for efficient hydrolysis of ceramide by acid ceramidase.
Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms.

PURPOSE This phase I trial was undertaken to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the B-cell-restricted immunotoxin anti-B4-blocked ricin (anti-B4-bR) when it is administered by 7-day continuous infusion. PATIENTS AND METHODS Thirty-four patients with relapsed and refractory B-cell neoplasms (26 non-Hodgkin's lymphoma [NHL], four chronic lymphocytic leukemia [CLL], four acute lymphoblastic leukemia [ALL]) received 7-day continuous infusion anti-B4-bR. Successive cohorts of at least three patients were treated at doses of 10 to 70 micrograms/kg/d for 7 days with the dose increased by 10 micrograms/kg/d for each cohort. The initial three cohorts of patients (10, 20, and 30 micrograms/kg/d x 7 days) also received a bolus infusion of 20 micrograms/kg before beginning the continuous infusion. RESULTS The MTD was reached at 50 micrograms/kg/d x 7 days. The DLTs were National Cancer Institute Common Toxicity Criteria (NCI CTC) grade IV reversible increases in AST and ALT, and grade IV decreases in platelet counts. Adverse reactions included fevers, nausea, headaches, myalgias, hypoalbuminemia, dyspnea, edema, and capillary leak syndrome. Potentially therapeutic serum levels of anti-B4-bR could be sustained for 4 days in patients treated at the MTD. Two complete responses (CRs), three partial responses (PRs), and 11 transient responses (TRs) were observed. CONCLUSION Anti-B4-bR can be administered safely by 7-day continuous infusion with tolerable, reversible toxicities to patients with relapsed B-cell neoplasms. Although occasional responses were seen, future trials will use anti-B4-bR in patients with lower tumor burdens to circumvent the obstacle of immunotoxin delivery to bulk disease.
The First Korean Case of Disseminated Mycetoma Caused by Nocardia pseudobrasiliensis in a Patient on Long-Term Corticosteroid Therapy for the Treatment of Microscopic Polyangiitis

Nocardia pseudobrasiliensis is predominantly associated with invasive infections in immunocompromised patients. We report a case of disseminated mycetoma caused by N. pseudobrasiliensis in a 57-yr-old woman with microscopic polyangiitis, who was treated for 3 months with corticosteroids. The same organism was isolated from mycetoma cultures on the patient's scalp, right arm, and right leg. The phenotypic characteristics of the isolate were consistent with both Nocardia brasiliensis and N. pseudobrasiliensis, i.e., catalase and urease positivity, hydrolysis of esculin, gelatin, casein, hypoxanthine, and tyrosine, but no hydrolysis of xanthine. The isolate was identified as N. pseudobrasiliensis based on 16S rRNA and hsp65 gene sequencing. The patient was treated for 5 days with intravenous ampicillin/sulbactam, at which time both the mycetomas and fever had subsided and discharged on amoxicillin/clavulanate. This case highlights a very rare presentation of mainly cutaneous mycetoma caused by N. pseudobrasiliensis. This is the first reported case of N. pseudobrasiliensis infection in Korea.
Observing Brownian motion and measuring temperatures in vibration-fluidized granular matter

Understanding the behaviour of granular media, either at rest or moving under external driving, is a difficult task, although it is important and of very practical interest. Describing the motion of each individual grain is complicated, not only because of the large number of grains, but also because the mechanisms of interaction at the grain level involve complex contact forces. One would like to have, in fact, a description in terms of a few macroscopic quantities. Since a granular medium resembles a liquid or a gas when strongly vibrated or when flowing out of a container, a natural approach is to adopt usual equilibrium statistical mechanics tools in order to test if such a macroscopic description is possible. In other words, an interesting question is to investigate whether one can model granular media, when close to a liquid-like state for example, using viscosity, temperature, and so on, as one does for normal liquids. With this aim in view, we have developed a non-equilibrium version of the classical Brownian motion experiment. In particular, we have observed the motion of a torsion oscillator immersed in an externally vibrated granular medium of glass spheres, and have collected evidence that the motion is Brownian-like. An approximate fluctuation–dissipation relation holds, and we can define temperature-like and viscosity-like parameters.
The Effect of Corporate Governance on the Performance of US Investment Banks

This paper focuses on the impact of the corporate governance, using a plethora of measures, on the performance of the US investment banks over the 2000–2012 period. This time period offers a unique set of information, related to the credit crunch, that we model using a dynamic panel threshold analysis to reveal new insights into the relationship between corporate governance and bank performance. Results show that the board size asserts a negative effect on performance consistent with the ‘agency cost ’ hypothesis, particularly for banks with board size higher than ten members. Threshold analysis reveals that in the post-crisis period most of investment banks opt for boards with less than ten members, aiming to decrease agency conflicts that large boards suffer from. We also find a negative association between the operational complexity and performance. Moreover, the CEO power asserts a positive effect on performance consistent with the ‘ stewardship ’ hypothesis. In addition, an increase in the bank ownership held by the board has a negative impact on performance for banks below a certain threshold. On the other hand, for banks with board ownership above the threshold value this effect turns positive, indicating an alignment between shareholders’ and managers’ incentives.
The Effect of Heavy Metal Ions and Their Complexions upon Growth, Sporulation and Pathogenicity of the Entomopathogenic Fungus Paecilomyces farinosus

Heavy metal ions are harmful for entomopathogenic fungi. Derivatives of starch dialdehyde such as dihydrazone (DHZ), dithiosemicarbazone (DTSC), and dioxime (DOX) were used to form water-insoluble complexes with heavy metal ions. This phenomenon thus provided protection of entomopathogenic fungus Paecilomyces farinosus from the toxic effects of heavy metal ions. The fungus growth and the sporulation of mycelium was inhibited by heavy metal ions. This fungus grown on medium with heavy metal ions was also less pathogenic to tested insects. Because the metal complexes of DHZ, DTSC and DOX were non-toxic to P. farinosus these complexons could protect entomopathogenic fungi from the toxic effects of metal ions, given good approximation of empirical values.
Allosteric Response and Substrate Sensitivity in Peptide Binding of the Signal Recognition Particle

Background: The SRP is a central component of the co-translational protein targeting pathway. Results: Long timescale computer simulations reveal shifts in the SRP conformational distribution upon nascent protein binding. Conclusion: The binding-induced conformational shifts correlate with the experimentally observed efficiency of protein targeting. Significance: The work provides new insight into the mechanism by which SRP allostery regulates the fidelity of protein targeting. We characterize the conformational dynamics and substrate selectivity of the signal recognition particle (SRP) using a thermodynamic free energy cycle approach and microsecond timescale molecular dynamics simulations. The SRP is a central component of the co-translational protein targeting machinery that binds to the N-terminal signal peptide (SP) of nascent proteins. We determined the shift in relative conformational stability of the SRP upon substrate binding to quantify allosteric coupling between SRP domains. In particular, for dipeptidyl aminopeptidase, an SP that is recognized by the SRP for co-translational targeting, it is found that substrate binding induces substantial changes in the SRP toward configurations associated with targeting of the nascent protein, and it is found that the changes are modestly enhanced by a mutation that increases the hydrophobicity of the SP. However, for alkaline phosphatase, an SP that is recognized for post-translational targeting, substrate binding induces the reverse change in the SRP conformational distribution away from targeting configurations. Microsecond timescale trajectories reveal the intrinsic flexibility of the SRP conformational landscape and provide insight into recent single molecule studies by illustrating that 10-nm lengthscale changes between FRET pairs occur via the rigid-body movement of SRP domains connected by the flexible linker region. In combination, these results provide direct evidence for the hypothesis that substrate-controlled conformational switching in the SRP provides a mechanism for discriminating between different SPs and for connecting substrate binding to downstream steps in the protein targeting pathway.
The Role of Risk Related Knowledge in the Diffusion of Internet Innovations

Several variables can influence the adoption of innovation. Human Computer Interaction research has focused on ease of use as the prime determinate of user satisfaction and adoption. This study explores the issues that influence the adoption, and further examines the knowledge of perceived risk as an influence. The study examines existing theory as it pertains to the diffusion of innovation from the perspective of the Internet, and assesses the extent to which Internet technology can be used in building long-term consumer relationships. Despite the high volume of shopping done on the Internet each day, many consumers fail to make online purchases because of continued reluctance to engage in transactions with intermediaries that are not familiar and trusted. Based on the previous studies, this study posits that perceived risk for security of online transactions is one of the factors influencing online purchasing behaviour, and has an effect on the continued use.
Recent Advances in Ceramic Composite Substrate Materials for High-Density and High Reliability Packaging Applications

This paper reports the evaluation of novel large-area Carbon-Silicon Carbide (C-SiC) based composite board material that has the advantages of organic boards in terms of large-area processability and machinability at potentially lowcost while retaining the high stiffness (>250GPa) and Simatched CTE (~2.5ppm/°C) of ceramics. In this work test vehicles were fabricated using C-SiC boards for assessing ultra-fine pitch solder joint reliability without underfill as well as the reliability of high-density wiring on the board. Finite element models were developed to simulate the thermomechanical behavior of test vehicles. From finite-element simulations as well as thermal-shock reliability tests, it was observed that high-stiffness low-CTE C-SiC boards do not show any premature solder-joint fatigue failure or dielectric cracking. Furthermore, the C-SiC boards show minimal via-pad misalignment supporting the multilayer build-up structure required to achieve very high wiring density. The modeling and experimental results suggest that the novel low-cost large-area ceramic matrix composite (CSiC) has required thermomechanical properties, and is therefore a promising candidate substrate material for nextgeneration microsystems.
Sensitivity of rat frontal cortical neurones to nicotine is increased by chronic administration of nicotine and by lesions of the nucleus basalis magnocellularis: Comparison with numbers of [3H]nicotine binding sites

The effects of chronic nicotine treatment and of unilateral AMPA lesion of the nucleus basalis magnocellularis (nbm) on the sensitivity of frontal cortical neurones to iontophoretically applied nicotine were studied. Chronic nicotine treatment increased the number of L3H1nicotine binding sites from 2.9 to 3.9 pmolg−1 wet weight, and increased the proportion of cortical neurones responding to nicotine from 32.3% to 60.0%. After unilateral nbm lesions, the densities of AChE‐positive fibers and [3H]nicotine binding sites were reduced by approximately 97% and 55%, respectively, and the proportion of neurones responding to nicotine increased from 32.3% to 53.8%. The two treatments, chronic nicotine administration and nbm lesion, also increased the size of individual neuronal responses, prolonged their duration, and shortened the response latency. Responses to glutamate were unaffected by either procedures. The results show that the increase in [3H]nicotine binding produced by chronic nicotine administration is associated with an increased response to iontophoretically applied nicotine, suggesting that the receptor upregulation induced by the chronic treatment were functional. Less easily explained is the association between increased sensitivity of frontal cortical neurons to nicotine after nbm lesion with a decreased receptor density. It is suggested that a substantial proportion of nicotinic receptors are located presynaptically, and that their loss after lesion concealed an upregulation at postsynaptic sites. © 1995 Wiley‐Liss, Inc.
Limiting ventilator-induced lung injury through individual electronic medical record surveillance*

Background:To improve the safety of ventilator care and decrease the risk of ventilator-induced lung injury, we designed and tested an electronic algorithm that incorporates patient characteristics and ventilator settings, allowing near-real-time notification of bedside providers about potentially injurious ventilator settings. Methods:Electronic medical records of consecutive patients who received invasive ventilation were screened in three Mayo Clinic Rochester intensive care units. The computer system alerted bedside providers via the text paging notification about potentially injurious ventilator settings. Alert criteria included a Pao2/Fio2 ratio of <300 mm Hg, free text search for the words “edema” or “bilateral + infiltrates” on the chest radiograph report, a tidal volume of >8 mL/kg predicted body weight (based on patient gender and height), a plateau pressure of >30 cm H2O, and a peak airway pressure of >35 cm H2O. Respiratory therapists answered a brief online satisfaction survey. Ventilator-induced lung injury risk was compared before and after the introduction of ventilator-induced lung injury alert. Findings:The prevalence of acute lung injury was 42% (n = 490) among 1,159 patients receiving >24 hrs of invasive ventilation. The system sent 111 alerts for 80 patients, with a positive predictive value of 59%. The exposure to potentially injurious ventilation decreased after the intervention from 40.6 ± 74.6 hrs to 26.9 ± 77.3 hrs (p = .004). Interpretations:Electronic medical record surveillance of mechanically ventilated patients accurately detects potentially injurious ventilator settings and is able to influence bedside practice at moderate costs. Its implementation is associated with decreased patient exposure to potentially injurious mechanical ventilation settings.
Expression of interleukin-8 in human obstructive pancreatitis.

CONTEXT Obstructive pancreatitis is a specific form of pancreatitis, which is caused by the obstruction of the main pancreatic duct due to tumors or some other causes. Interleukin-8 is induced in acute pancreatitis, but its expression in obstructive pancreatitis has not been clarified. OBJECTIVE We attempted to provide some insight into the significance of interleukin -8 in the pathogenesis of pancreatic fibrosis. PATIENTS Fifteen cases of pancreatic cancer, 7 cases of mucinous cystadenoma, 3 cases of Vater's papilla cancer and 9 normal pancreases were included in this study. MAIN OUTCOME MEASURES The obstructive pancreatitis portions of the above pathologies were evaluated for interleukin-8 expression by means of immunohistochemistry and in situ hybridization. RESULTS Interleukin-8 was positive in 72% of cases of obstructive pancreatitis. The positive rate was not significantly related to the etiology of the obstruction (P=0.972). Interleukin-8 was expressed in infiltrating cells, proliferating ductular cells and acinar cells. In contrast, normal pancreases and tumor cells lacked interleukin-8 expression (P<0.001 vs. obstructive pancreatitis). Both immunohistochemistry and in situ hybridization demonstrated that interleukin-8 was expressed mostly in acinar cells in mild pancreatic fibrosis, whereas it was expressed in stromal and ductular cells in moderate and severe pancreatic fibrosis. CONCLUSIONS These results suggest that interleukin-8 expression is related to the fibrotic process in obstructive pancreatitis.
Equivalence of Short Circuits between SIRW with Cylinder Wall and Regular Waveguide with Solid Wall

In this paper, the formula of equivalence of short locations of SIRW (with shorting cylinder wall) from the rectangular waveguide (RW) (with shorting solid wall) has been obtained. The similarity between components of the plane propagation-constant in the waveguide means that the formulas of short location are directly converted from the formula of width equivalence of SIRW from RW, the width formula has been verified to be accurate. The results have shown that, the width equivalence between SIRW and RW depends on the width of SIRW, cylinder radius and separation, being independent with frequency. However, the location equivalence from cylinder short wall to solid short wall depends on the frequency, although the dependence is still small. To end, it may be noted that the formulas apply only to quasi-static separation W of the cylinders along the shorting wall, i.e., W les lambdag/20. If the cylinder radius R < W/4, there will be power leakage out of the SIRW short. This leakage is to be studied
On the Performance of the Zoned Fishnet Metamaterial Lens With Positive and Negative Reference Phase

In this letter, several converging fishnet metalenses are designed using both the zoning and reference phase techniques. They are engineered with a focal length of 1. 5λ<sub>0</sub> at the design frequency of 55 GHz (λ<sub>0</sub> = 5.45 mm) at which the fishnet metamaterial has an effective refractive index of <inline-formula><tex-math notation="LaTeX">$n$</tex-math></inline-formula><italic><sub>lens</sub></italic> = ∼0.68. Three metalenses are analyzed—with positive, negative, and without reference phase—in order to compare their performance. The focal properties are evaluated both numerically and experimentally, demonstrating a good agreement between them. The best performance is achieved for the zoned metalens with positive reference phase, with an experimental power enhancement at the focal length of 6.2 dB, better axial resolution (0.65λ<sub>0</sub> ), and reduced lateral lobes compared to the other designs.
Increasing nitrogen rates in rice and its effect on plant nutrient composition and nitrogen apparent recovery

Rice ( Oryza sativa L.) is one of the essential foods of the human diet; advances in agronomic crop management can improve productivity and profitability as well as reduce adverse environmental impacts. Nitrogen rates in Chile are generally based on crop yield without considering other agronomic factors. The objective of this experiment was to determine the effect of increasing N rates on plant nutrient composition and N apparent recovery in rice cultivated in five different locations in Chile. The five sites located in central Chile belong to one of the following soil orders: Inceptisol, Alfisol, and Vertisol; they were cropped in field conditions with ‘Zafiro-INIA’ rice fertilized with 0, 80, and 160 kg N ha-1. Whole-plant total DM, macronutrient composition, and N apparent recovery efficiency (NARE) were determined at grain harvest. Results indicate that all evaluated parameters, with the exception of K concentration, were affected by the soil used. Nitrogen rates only affected total DM production and P, K, and Mg concentrations in plants. Phosphorus and K response decreased when N was added to some soils, which is associated with its chemical properties. Magnesium concentration exhibited an erratic effect, but it wasSnot affected by the N rate in most soils. Nitrogen apparent recovery efficiency was not affected by the N rate and accounted for approximately 49% and 41% for 80 and 160 kg N ha-1, respectively. Macronutrient composition was 5.1-7.7 g N, 1.3-1.8 g P, 5.4-10.8 g K, 1.68-2.57 g Ca, and 0.81-1.45 g Mg kg-1 of total DM.
Heparan sulfate proteoglycans in the nervous system: their diverse roles in neurogenesis, axon guidance, and synaptogenesis.

Development of the mammalian nervous system involves generation of neurons from neural stem cells, migration of generated neurons toward genetically determined locations, extension of axons and dendrites, and establishment of neuronal connectivity. Recent progresses revealed diverse role of heparan sulfate proteoglycans in these processes. This article reviews our current knowledge about the functional roles of heparan sulfate proteoglycans in three critical events in mammalian neural development, namely neurogenesis, axon guidance, and synapse development.
Memory T lymphocyte hyporesponsiveness to non‐cognate stimuli: a key factor in age‐related immunodeficiency

Previous studies from our laboratory have suggested that aging leads to an accumulation of cells expressing high levels of CD44, thought to be a marker for memory lymphocytes, and that positively selected CD44hi T cells, from mice of any age, respond poorly to concanavalin A (Con A) in limiting dilution estimates of interleukin (IL)‐2‐producing cells. We now report the results of a more comprehensive analysis of memory T cell function, in old and young mice, to non‐cognate activators (Con A and the staphylococcal enterotoxin SEB). We report that memory T cells, isolated by removing cells bearing the CD45RB determinant, contain very few cells able to respond to either Con A or SEB under limiting dilution culture conditions, whether the responses are measured by IL‐2 or by IL‐3 accumulation. As a control, we show that memory T cells do respond strongly, at limiting dilution, to recently encountered priming antigens, i.e. Schistosoma mansoni egg antigen; the limiting dilution culture protocol thus does not preclude activation of memory T cells when cognate stimuli are presented to antigen‐specific cells. These data suggest that virgin and memory T cells may differ fundamentally in their activation requirements, and suggest further that the accumulation, with age, of memory T cells accounts for the low responsiveness of old mice to non‐cognate mitogens.