Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacologic manipulation of sphingosine kinase in retinal endothelial cells: implications for angiogenic ocular diseases.

PURPOSE The increased vascular permeability and pathogenic angiogenesis observed in diabetic retinopathy are induced, at least in part, by local inflammation and vascular endothelial growth factor (VEGF). Therefore, inhibition of signaling from VEGF and tumor necrosis factor-alpha (TNFalpha) is a promising approach to the treatment of this disease, as well as ocular diseases with similar etiologies, including age-related macular degeneration. A growing body of evidence demonstrates that sphingosine kinase (SK) plays an important role in cellular proliferation and angiogenesis. This study was undertaken to examine the effects of SK inhibitors on the responses of retinal endothelial cells (RECs) to VEGF and TNFalpha and their therapeutic efficacy in a diabetic retinopathy model. METHODS The expression and function of SK in bovine and human RECs were examined by immunoblot analysis. The involvement of SK in mediating responses to VEGF and TNFalpha was examined by using pharmacologic inhibitors of SK in cellular and in vivo assays, including a 3-month streptozotocin-induced diabetic retinopathy model in rats. RESULTS SK was present and active in human and bovine RECs, and SK activity in these cells was stimulated by VEGF. Inhibitors of SK blocked VEGF-induced production of sphingosine 1-phosphate and markedly attenuated VEGF-induced proliferation and migration of RECs. In addition, SK inhibitors were shown to block TNFalpha-induced expression of adhesion proteins, suppress VEGF-induced vascular leakage in an in vivo mouse model, and reduce retinal vascular leakage in the rat diabetic retinopathy model. CONCLUSIONS Overall, these studies demonstrate that inhibitors of SK attenuate the effects of proliferative and inflammatory stimuli on RECs both in vitro and in vivo, and so could be significant therapeutics in the treatment of diabetic retinopathy.
Impaired Innate Mucosal Immunity in Aged Mice Permits Prolonged Streptococcus pneumoniae Colonization

ABSTRACT Streptococcus pneumoniae is a frequent asymptomatic colonizer of the nasopharyngeal niche and only occasionally progresses toward infection. The burden of pneumococcal disease is particularly high in the elderly, and the mechanisms behind this increased susceptibility are poorly understood. Here we used a mouse model of pneumococcal carriage to study immunosenescence in the upper respiratory tract (URT). Nasal mucosa-associated lymphoid tissue (NALT) showed increased expression of Toll-like receptor 1, interleukin-1β, NLRp3 inflammasome, and CCL2 in naive elderly compared to young animals. This suggests an increased proinflammatory expression profile in the NALT of aged mice at baseline. Simultaneously, we observed a more tolerogenic profile in respiratory epithelia of naive elderly compared to young adult mice with upregulation of the NF-κβ pathway inhibitor peroxisome proliferator-activated receptor gamma (PPARγ). After nasal instillation of pneumococci, pneumococcal colonization was prolonged in elderly mice compared to in young adults. The delay in clearance was associated with absent or delayed upregulation of a proinflammatory mediator(s) in the NALT, diminished influx of macrophages into the URT niche, and absent downregulation of PPARγ in respiratory epithelium, accompanied by diminished expression of cathelicidin (CRAMP) at the site of colonization. These findings suggest that unresponsiveness to pneumococcal challenge due to altered mucosal immune regulation is the key to increased susceptibility to disease in the elderly.
Pressure-induced solid-state lattice mending of nanopores by pulse laser annealing

This paper presents the pressure-induced solid-state lattice mending of nanopores in single-crystal copper by femtosecond laser annealing processes. The microscopic mechanism of lattice mending is investigated by a modified continuum–atomistic modeling approach. Three typical lattice mending phases, including (i) the incubation of dislocation nucleation, (ii) plastic deformation under the combined effect of pressure and atomic thermal diffusion, and (iii) lattice recovery and reconstruction, are characterized via the microscopic structure changes and transient thermodynamic trajectories. The simulation results reveal that the structural mending of a pore is originated in heterogeneous nucleation of dislocations from the pore surface. The shear-induced multiple lattice glides are found to significantly contribute to the mending of a nanopore in the process of solid-state structural mending. The mending rates of two different modes, the pressure-induced and the classical unsteady-state atomic diffusion, are estimated and found to be very different from each other, by an order of 104. In addition, the location of the pore is also found to significantly influence the annealing threshold. Since the largest amplitude of the pressure wave is built up at a characteristic depth of approximately 45 nm below the irradiated surface, the shock wave will directly impinge on the pore and induce a fast solid-state lattice mending if the pore is located within the lower limit of the range of the characteristic depth. Furthermore, it is also interesting to note that the mending of a nanopore close to the characteristic depth by annealing fluence is generally lower than that of a pore near the surface. These results provide vital insights of photomechanical interactions with the microstructure of metallic solid, and the proposed approach can be further considered and enhanced to predict the mending depth for various defects in the future.
Detection of Postoperative Surgical-Site Infections: Comparison of Health Plan–Based Surveillance With Hospital-Based Programs

Abstract Background: Review of health plan administrative data has been shown to be more sensitive than other methods for identifying postdischarge surgical-site infections (SSIs), but there has not been a direct comparison between this method and hospital-based surveillance for all infections, including those diagnosed before discharge. We compared these two methods for identifying SSIs following coronary artery bypass graft (CABG) procedures:. Methods: We studied 1,352 CABG procedures performed among members of one health plan from March 1993 through June 1997. Health plan administrative records were reviewed based on claims containing diagnoses or procedures suggestive of infection or outpatient dispensing of antibiotics appropriate for SSI. Hospital-based surveillance information was also reviewed. SSI rates were calculated based on the total events identified by either mechanism. Results: Postdischarge information was reviewed for 328 (85%) of 388 procedures. SSIs were confirmed in 167 patients (13% overall risk of confirmed SSI; range, 3% to 14% in the 5 hospitals). The overall sensitivity of hospital-based surveillance was 49.7% (83 of 167), and that of health plan data was 71.8% (120 of 167). There was no significant difference among hospitals in the sensitivity of either surveillance mechanism. Conclusions: Surveillance based on health plan data identified more postoperative infections, including those occurring before discharge, than did hospital-based surveillance. Screening administrative data and pharmacy activity may be an important adjunct to SSI surveillance, allowing efficient comparison of hospital-specific rates. Interpretation of differences among hospitals' infection rates requires case mix adjustment and understanding of variations in hospitals' discharge diagnosis coding practices
Palacos gentamicin for the treatment of deep periprosthetic hip infections.

Between 1983 and 1986, 40 hip arthroplasties in 40 patients with documented deep infection were reimplanted using Palacos Gentamicin at The Hospital for Special Surgery. Palacos Gentamicin was added to the standard protocol, which included removal of the prosthesis, cement, if present, and a thorough debridement of infected and necrotic tissue, six weeks of intravenous antibiotics with a postpeak serum bactericidal titer of at least 1:8 against the infecting bacteria, followed by reimplantation of the hip. Sixteen of the patients also had the placement of gentamicin-impregnated beads at the time of prosthetic removal. All patients had a deep periprosthetic infection, 13 with Staphylococcus epidermidis, seven Staphylococcus aureus, four Streptococcus, three Enterococcus, three with gram-positive bacteria, four Escherichia coli, two Proteus, one Pseudomonas, and three anaerobic organisms. At an average follow-up period of five years (range, two to ten), two of the 40 hips (5%) developed recurrent infection. These cases recurred at one month in a patient immunocompromised by end-stage systemic lupus erythematosus (S. epidermidis) and at five months in a patient with severe titanium metallosis (S. aureus). No recurrence was noted in eight cases with gram-negative organisms or in three cases of mixed infections. No infection recurred after five months in the remaining patients before their death or last follow-up examination. Of the remaining 38 hips, 16 died of causes unrelated to the hip, leaving 21 with an average follow-up period of 7.5 years. Clinical results in these patients were 14 excellent, five good, two fair, and no poor results. (ABSTRACT TRUNCATED AT 250 WORDS)
Expression of retinol‐binding protein and cellular retinol‐binding protein in the bovine ovary

Retinol (vitamin A) is essential for reproduction, and retinoids have been suggested to play a role in ovarian steroidogenesis, oocyte maturation, and early embryonic development. Retinol is transported systemically and intercellularly by retinol‐binding protein (RBP). Within the cell, cellular retinol‐binding protein (CRBP) functions in retinol accumulation and metabolism. Since the actions of retinoids are mediated, in part, by retinoid‐binding proteins, the objective of this study was to investigate cell‐specific expression of RBP and CRBP in the bovine ovary. Immunocytochemical analysis (ICC) localized RBP to the thecal and granulosa cell layers of antral and preantral follicles with the most intense staining in the cells of large, healthy follicles. The tunica adventitia of arterial blood vessels also exhibited RBP staining. Immunostaining of CRBP was most intense in the granulosa cells of preantral follicles and present, but diminished, in thecal and granulosa cells of antral follicles. Within the corpus luteum, both proteins were observed in large luteal cells, but only RBP was observed in small luteal cells. Northern blot analysis demonstrated that thecal and granulosa cells from antral follicles and luteal tissue expressed RBP and CRBP mRNA. Synthesis and secretion of RBP by thecal cells, granulosa cells, and luteal cells were demonstrated by immune‐complex precipitation of radiolabeled RBP from the medium of cultured cells or explants, followed by SDS–PAGE and fluorography. Follicular fluid was collected from small (<5 mm) and large (8–14 mm) follicles, pooled according to follicular size, and analyzed for retinol, RBP, estradiol‐17β, and progesterone. Concentrations of retinol, RBP, and estradiol were greater in the fluid of large follicles. Results demonstrate retinoid‐binding protein expression by bovine ovaries and provide physical evidence that supports the concept that retinoids play a role in ovarian function. Mol. Reprod. Dev. 64: 261–269, 2003. © 2003 Wiley‐Liss, Inc.
Preliminary Experience with the Percutaneous Embolization of Juvenile Angiofibromas Using Only Ethylene-Vinyl Alcohol Copolymer (Onyx) for Preoperative Devascularization Prior to Surgical Resection

BACKGROUND AND PURPOSE: Juvenile angiofibromas are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss. Our purpose was to evaluate the extent of angiographic devascularization and intraoperative blood loss by using only Onyx for percutaneous juvenile angiofibroma tumor embolization. MATERIALS AND METHODS: We reviewed the clinical records and preoperative and postoperative imaging studies of a consecutive series of 9 patients with juvenile angiofibromas who were treated with preoperative embolization with direct percutaneous injection of Onyx followed by resection from a standard open surgical or endoscopic approach. RESULTS: Two Fisch type I, 1 Fisch type II, 5 Fisch type IIIa, and 1 Fisch type IVa tumor were treated. Complete devascularization was achieved in all cases percutaneously with only Onyx. There were no complications. The average intraoperative blood loss was 567.7 mL (range, 10–1700 mL). An average of 2.2 needles (range, 1–5 needles) was placed into the tumor. An average of 14.6 mL of Onyx (range, 2–25 mL) was injected into each tumor. Four Fisch type IIIa tumors were removed completely from only an ENE approach. CONCLUSIONS: Presurgical direct percutaneous embolization of a juvenile angiofibroma with only EVOH before surgical resection is safe and feasible. Our preliminary experience suggests that Onyx may offer a higher degree of devascularization compared with other embolic agents. This may facilitate an easier surgical resection with lower blood loss.
Grid-connected inverter power flow control based on a new modeling approach of electrical signals

The authors have recently presented a new modeling approach for electrical signals in power systems. A significant advantage lies in the possibility to define quantities typically considered in sinusoidal steady-state conditions also during the transients. This paper presents a power flow control strategy, based on the aforesaid approach, for a PWM inverter able to support bidirectional power flow and so to operate as efficient interface between a DC power source (for example a photovoltaic source) and the power distribution grid.
Price Formation: the Case of the Burgundy

Price formation processes in "quality" commodities markets challenge standard eco nomic theory. Using the principle of "embeddedness" postulated by economic sociology, the article shows how price formation analysis can reveal the social organization of such mar kets. A comprehensive approach to how wine producers in Burgundy determine their prices shows how the diversity of procedures used is related to professional relations and statuses. Using "integration variables" that are both economic and sociological, the discussion opens onto perspectives for renewing dialogue between the two disciplines and thus furthering our understanding of "the economics of quality".
Can current analytical quality performance of UK clinical laboratories support evidence-based guidelines for diabetes and ischaemic heart disease? – A pilot study and a proposal

Abstract Background: The implementation of national and international guidelines is beginning to standardise clinical practice. However, since many guidelines have decision limits based on laboratory tests, there is an urgent need to ensure that different laboratories obtain the same analytical result on any sample. A scientifically-based quality control process will be a pre-requisite to provide this level of analytical performance which will support evidence-based guidelines and movement of patients across boundaries while maintaining standardised outcomes. We discuss the finding of a pilot study performed to assess UK clinical laboratories readiness to work to a higher grade quality specifications such as biological variation-based quality specifications. Methods: Internal quality control (IQC) data for HbA1c, glucose, creatinine, cholesterol and high density lipoprotein (HDL)-cholesterol were collected from UK laboratories participating in the Bio-Rad Unity QC programme. The median of the coefficient of variation (CV%) of the participating laboratories was evaluated against the CV% based on biological variation. Results: Except creatinine, the other four analytes had a variable degree of compliance with the biological variation-based quality specifications. More than 75% of the laboratories met the biological variation-based quality specifications for glucose, cholesterol and HDL-cholesterol. Slightly over 50% of the laboratories met the analytical goal for HBA1c. Only one analyte (cholesterol) had a performance achieving the higher quality specifications consistent with 5σ. Conclusions: Our data from IQC do not consistently demonstrate that the results from clinical laboratories meet evidence-based quality specifications. Therefore, we propose that a graded scale of quality specifications may be needed at this stage.
Computing Posterior Probabilities for Score-based Alignments Using ppALIGN

Score-based pairwise alignments are widely used in bioinformatics in particular with molecular database search tools, such as the BLAST family. Due to sophisticated heuristics, such algorithms are usually fast but the underlying scoring model unfortunately lacks a statistical description of the reliability of the reported alignments. In particular, close to gaps, in low-score or low-complexity regions, a huge number of alternative alignments arise which results in a decrease of the certainty of the alignment. ppALIGN is a software package that uses hidden Markov Model techniques to compute position-wise reliability of score-based pairwise alignments of DNA or protein sequences. The design of the model allows for a direct connection between the scoring function and the parameters of the probabilistic model. For this reason it is suitable to analyze the outcomes of popular score based aligners and search tools without having to choose a complicated set of parameters. By contrast, our program only requires the classical score parameters (the scoring function and gap costs). The package comes along with a library written in C++, a standalone program for user defined alignments (ppALIGN) and another program (ppBLAST) which can process a complete result set of BLAST. The main algorithms essentially exhibit a linear time complexity (in the alignment lengths), and they are hence suitable for on-line computations. We have also included alternative decoding algorithms to provide alternative alignments. ppALIGN is a fast program/library that helps detect and quantify questionable regions in pairwise alignments. Due to its structure, the input/output interface it can to be connected to other post-processing tools. Empirically, we illustrate its usefulness in terms of correctly predicted reliable regions for sequences generated using the ROSE model for sequence evolution, and identify sensor-specific regions in the denitrifying betaproteobacterium Aromatoleum aromaticum.
Localization of Mu and Delta Opioid Receptors to Anterior Cingulate Afferents and Projection Neurons and Input/Output Model of Mu Regulation

Anterior cingulate cortex (ACC) has one of the highest densities of opioid receptors in the CNS and it has been implicated in acute and chronic pain responses. Little is known, however, about which neurons express opioid receptors in their dendrites and axon terminals. The present studies employed experimental techniques to remove afferent axons or classes of projection neurons from rat ACC area 24 followed by coverslip autoradiography to localize changes in binding of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO) to mu receptors and 2-[3H]D-penicillamine-5-D-penicillamine-enkephalin (DPDPE) to delta receptors. Removal of all afferents to area 24 with undercut lesions did not alter DPDPE binding, but significantly reduced binding of DAMGO in layers I, III, and V. In contrast, removal of all cortical neurons with the excitotoxin ibotenic acid almost abolished DPDPE binding in all layers. The same lesions reduced DAMGO binding in most layers; however, there was a postlesion bimodal distribution in binding with high levels of binding in layer I and moderate levels in layer VI. These data suggest that delta receptors are expressed by cortical neurons, while mu receptors are expressed by both cortical neurons and afferent axons. To explore the distribution of postsynaptic receptors, immunotoxin lesions were made in area 24 by injection of OX7-saporin into the caudate and/or thalamic nuclei. Almost complete removal of projection neurons to these targets in layers Vb and VIa did not alter DPDPE binding, while the lesions reduced DAMGO binding in all but layer II. Removal of layer Vb corticostriatal projection neurons with caudate OX7-saporin injections reduced binding only in this layer. It is proposed that opioidergic circuits in area 24 are organized according to an input/output model for mu opioid regulation. In this model mu receptors regulate axon terminal activity from the thalamus in layer Ia and the locus coeruleus in layers Ic and II, whereas cortical outputs to the thalamus are modulated via postsynaptic receptors expressed in all layers by thalamocortical projection neurons with somata in layer VI. These opioidergic circuits in ACC are of particular importance because they may regulate responses to chronic nociceptive activity and associated pain perceptions.
Time stability of Stress Induced Leakage Current in thin gate oxides

We have investigated the time stability of low-field Stress Induced Leakage Current (SILC) in thin oxides. By injecting a low gate current, SILC can be strongly reduced at room temperature. This behaviour may be attributed to electron trapping in those weak spots generated by the electrical stress. In absence of charge injection, SILC is not healed during room temperature storage periods. The optimal conditions for SILC abatement have been experimentally investigated No saturation value of SILC decay has been found, challenging the significance of the SILC DC steady state value.
Relationship between binge-eating episodes and self-perception of body weight in a nonclinical sample of five Brazilian cities.

OBJECTIVE To investigate the relationship between binge-eating episodes and a perception that body weight is above the ideal in a sample of customers interviewed at shopping malls in five Brazilian cities. METHODS In 1999, data were collected over the course of one week (Monday-Friday only) at the largest shopping malls in the cities of Porto Alegre, Salvador, Fortaleza, Goiânia and Curitiba (two malls per city). A total of 2855 participants (917 men and 1938 women) were interviewed. Weight and height measurements were standardized. Binge-eating episodes were identified using a questionnaire including the following questions based on DSM-IV diagnostic criteria: "Have you ever eaten, in a period of two hours or less, an amount of food greater than that most people would eat? " and "If the answer was "yes", did you, during these episodes, feel unable to stop eating or to control how much you were eating? ". RESULTS The prevalence of binge-eating episodes was higher among overweight subjects (15.6%) compared with normal-weight subjects (9.9%) (p = 0.0001) and, among subjects who perceived their body weight to be above the ideal (men: 13.9%; women: 15.1%) compared with those who perceived their body weight to be ideal or below the ideal (men: 8%; women: 7%) (p < 0.0001). In the multivariate analysis adjusted for body mass index and demographic variables, binge-eating episodes were correlated with the perception that body weight is above the ideal only among women (OR: 1.8; 95% CI: 1.2-2.5). CONCLUSIONS These findings suggest that the perception that body weight is above the ideal, regardless of overweight status, is associated with binge-eating episodes in women.