Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular accumulation of the new ketolide RU 64004 by human neutrophils: comparison with that of azithromycin and roxithromycin

We analyzed the uptake of RU 64004 by human neutrophils (polymorphonuclear leukocytes [PMNs]) relative to those of azithromycin and roxithromycin. RU 64004 was strongly and rapidly accumulated by PMNs, with a cellular concentration/extracellular concentration ratio (C/E) of greater than 200 in the first 5 min, and this was followed by a plateau at 120 to 180 min, with a C/E of 461 +/- 14.8 (10 experiments) at 180 min. RU 64004 uptake was moderately sensitive to external pH, and activation energy was also moderate (63 +/- 3.8 kJ/mol). RU 64004 was mainly located in PMN granules (about 70%) and egressed slowly from loaded cells, owing to avid reuptake. The possibility that PMN uptake of RU 64004 and other macrolides occurs through a carrier-mediated system was suggested by three key results. First, there existed a strong interindividual variability in uptake kinetics, suggesting variability in the numbers or activity of a transport protein. Second, macrolide uptake displayed saturation kinetics characteristic of that of a carrier-mediated transport system: RU 64004 had the highest Vmax value (3,846 ng/2.5 x 10(6) PMNs/5 min) and the lowest Km value (about 28 microM), indicating a high affinity for the transporter. Third, as observed previously with other erythromycin A derivatives, Ni2+ (a blocker of the Na+/Ca2+ exchanger which mediates Ca2+ influx in resting neutrophils) impaired RU 64004 uptake by PMNs, with a 50% inhibitory concentration of about 3.5 mM. In addition, we found that an active process is also involved in macrolide efflux, because verapamil significantly potentiated the release of all three macrolides tested. This effect of verapamil does not seem to be related to an inhibition of Ca2+ influx, because neither EGTA [ethylene glycol-bis (beta-aminoethyl ether)-N,N',N'-tetraacetic acid] nor Ni2+ modified macrolide efflux. The nature and characteristics of the entry- and efflux-mediating carrier systems are under investigation.
The Impact of the Day of the Week and Month of Admission on the Length of Hospital Stay in Stroke Patients

Background: Length of hospital stay (LOS) in many diseases is determined by patient-related sociodemographic and clinical factors but also by the management of treatment and care. We examined the influence of the day of the week (DW) and month of admission on LOS in stroke patients. Methods: We used data from a large regional stroke registry in the northwest of Germany for the years 2000 and 2001. The registry is based on a standardised data assessment in participating hospitals, including patient-related sociodemographic and clinical items, diagnostic and treatment procedures, stroke classification, as well as admission and discharge dates. Data management and analysis were done centrally. Results: A total of 11,942 patients from 42 hospital departments were included. Median LOS was 13 days for ischemic stroke and 8 days for TIA. Patients with ischaemic stroke admitted on Tuesdays or Wednesdays had the longest LOS. We observed a significantly shorter LOS in patients discharged towards the weekend, both for ischaemic stroke and TIA, independent of age, gender and symptom severity. Discharges were predominantly done on Fridays (25%), transferrals to rehabilitation centres most often on Thursdays (28%) in neurologic departments but on Tuesdays in departments of internal medicine. LOS according to the month of admission revealed a biphasic curve for both ischaemic stroke and TIA, with shortest LOS in July and December. Conclusions: Discharge patterns on weekends contribute to differences in LOS for the various DWs of admission. Changes in discharge organisation and improved co-operation with rehabilitation centres may shorten LOS. Differences in LOS between the months show considerable seasonal variability.
Running Head : Climate change and oxidative damage in fish 3 Authors :

1 Title: Is warmer better? Decreased oxidative damage in notothenioid fish after long-term 1 acclimation to multiple stressors. 2 Running Head: Climate change and oxidative damage in fish 3 Authors: Laura A. Enzor and Sean P. Place* 4 Address: University of South Carolina 5 Department of Biological Sciences 6 Columbia, SC USA 29208 7 Current Address 8 Sonoma State University 9 Department of Biology 10 Rohnert Park, CA USA 94928 11 *Corresponding Author: Sean P. Place 12 ph: 1+ (803) 777-6597 13 fax: 1+ (803) 777-4002 14 email: places@mailbox.sc. edu 15
Vitamin D Receptor Interactions with the Rat Parathyroid Hormone Gene: Synergistic Effects Between Two Negative Vitamin D Response Elements

Vitamin D response elements (VDREs) that are required for negative regulation of rat parathyroid hormone (rPTH) gene expression have been characterized. Gel mobility shift assays using DNA restriction enzyme fragments and recombinant proteins for vitamin D and retinoic acid X receptors (VDR/RXR) revealed a sequence between −793 and −779 that bound a VDR/RXR heterodimer with high affinity (VDRE1). Furthermore, a lower affinity site (VDRE2) was detected that acted in combination with VDRE1 to bind a second VDR/RXR complex. As determined by ethylation interference analysis, the nucleotide sequence of VDRE1 consisted of GGTTCA GTG AGGTAC, which is remarkably similar to the sequence of the negative VDRE found in the chicken PTH (cPTH) gene. Using the same technique, VDRE2 was identified between positions −760 and −746 and contained the sequence AGGCTA GCC AGTTCA. Functional analysis was determined by transfection studies with plasmid constructs that expressed the gene for chloramphenicol acetyl transferase (CAT). The ability of the VDREs to regulate gene expression was tested in their native context with the rPTH promoter as well as when positioned immediately upstream from the cPTH promoter. With either plasmid construct, exposure to 10−8 M 1,25(OH)2D3 resulted in a 60–70% decrease in CAT gene expression when both VDRE1 and VDRE2 were present. Examination of the individual VDREs showed that inhibition by 10−8 M 1,25(OH)2D3 was only 35–40% when just VDRE1 was present. By itself, VDRE2 was even less effective, as significant inhibition of CAT activity (20%) was observed only in the presence of higher concentrations of 1,25(OH)2D3 (10−7 M) or when a plasmid vector that overexpressed the VDR protein was cotransfected. In conclusion, the rPTH gene contains two negative VDREs that act in concert to bind two RXR/VDR heterodimer complexes and that both VDREs are required for maximal inhibition by 1,25(OH)2D3.
Up‐regulation of pS2 expression during the development of adenocarcinomas but not squamous cell carcinomas of the uterine cervix, independently of expression of c‐jun or oestrogen and progesterone receptors

The pS2 gene product was firstly identified as an oestrogen‐induced molecule in a breast cancer cell line, while recent studies demonstrate a close association with mucus‐secreting epithelia. To assess pS2 expression in uterine cervical adenocarcinomas (C‐ACas) and invasive squamous cell carcinomas (C‐ISCCs), a series of 94 and 86 cases, respectively, as well as 77 samples of normal cervix, were immunohistochemically investigated and the results compared with data for expression of oestrogen and progesterone receptors (ER and PR) and c‐jun. RT‐PCR and western blot assays were also applied to 21 cervical carcinomas and 24 normal tissues. With cervical glandular lesions, significant up‐regulation of pS2 expression at both the mRNA and the protein levels was observed for adenocarcinomas in situ (AISs) and overt carcinomas, closely linked with mucinous differentiation and tumour grades. pS2 scores were inversely related to ERα status for all cervical glandular categories, while there was no association with ERβ and PR values. In squamous lesions, pS2 values did not differ between normal and malignant lesions, in contrast to the significant down‐regulation of ERα expression with tumour development. Although c‐jun expression significantly correlated with ERα values for all squamous categories, it did not relate to pS2 status in either C‐ACas or ISCCs. These results indicate that alterations in pS2 expression may occur relatively early in the development of cervical glandular, but not squamous lesions, independently of factors known to promote transcription of the pS2 gene. Copyright © 2000 John Wiley & Sons, Ltd.
School of Urban Studies and Planning 1-2019 A Comparison of Neighborhood-Scale Interventions to Alleviate Urban Heat in Doha , Qatar

Recent evidence suggests that many densely populated areas of the world will be uninhabitable in the coming century due to the depletion of resources, climate change, and increasing urbanization. This poses serious questions regarding the actions that require immediate attention, and opportunities to stave off massive losses of infrastructure, populations, and financial investments. The present study utilizes microclimate modeling to examine the role of landscape features as they affect ambient temperatures in one of the fastest growing regions of the world: Doha, Qatar. By modeling three study sites around Doha—one highly urbanized, one newly urbanizing, and one coastal low-density urbanized—the research indicates that at the neighborhood scale, the most effective scenario was that of adding mature trees along the sides of roads. In the coastal study area, the model results estimated a maximum hourly air temperature reduction of 1.35 ◦C, and in the highly urbanized inland site, surface temperature reductions were up to 15 ◦C at 12:00. While other scenarios were effective at reducing air and surface temperatures, the mean radiant temperature was also increased or nearly neutral for most of the other scenarios. This result highlights the need to develop improved shading measures for pedestrian pathways and outdoor recreational areas, especially for highly urbanized inland areas in Doha and cities with similar climatic conditions.
Epileptic seizure detection on patients with mental retardation based on EEG features: A pilot study

Mental retardation (MR) is one of the most common secondary disabilities in people with Epilepsy. However, to our knowledge there are no reliable seizure detection methods specified for MR-patients. In this paper we performed a pilot study on a group of six patients with mental retardation to assess what EEG features potentially work well on this group. A group of EEG features on the time, frequency and spatio-temporal domain were extracted, the modified wrapper approach was then employed as an improved feature subset selection method. Results show high variance on obtained features subset across this group, meanwhile there exist some common features which characterize the high-frequency components of epileptic EEG signals.
Conceptus Polarity and Cell-Zona Adhesion during Early Cleavage (Fertilized Tubal Egg to 8-Cell Stage) in the Marsupial Sminthopsis macroura

This study outlines the ultrastructural changes that occur in Sminthopsis macroura tubal zygotes to the 8-cell stage in relation to observations of development in vitro, oocyte polarity and cell-zona adhesion. The extremely polarized mature oocytes and zygotes have nuclear material at one pole and accumulated vesicular bodies at the other. The first division is associated with extrusion of vesicular bodies and some cytoplasm as a membrane-bound yolk mass into the perivitelline space. Early cleavage is accompanied by the appearance of an extensive, highly structured extracellular matrix (ECM) comprised of amorphous substance, granules and filaments. At the 2- and 4-cell stage the decrease in density of the ECM in the vicinity of the blastomeres may facilitate cell-zona contact. At the 8-cell stage, discharge of vesicular bodies, which mostly appear to be empty, may contribute to the ECM by increasing the area of plasma membrane for synthesis of a hyaluronan-like ECM. As in other marsupials, the precedence of cell-zona adhesion over cell-cell contacts prevents morula formation. The earliest cell-zona contacts appear when microvilli contact the zona in the uterine zygote 12–16 h after uterine entry and continue at later stages. This early contact is possible because of the absence of a dense subzonal ECM in this species. Between late zygote and late 4-cell stage the cytoplasm also contains, beside a large amount of vesicular bodies, demarcated areas where smooth endoplasmic reticulum encloses mitochondria, vesicles, granular material and fibrillar arrays. The latter develop in the late zygote stage and are found outside demarcated areas as well, often closely surrounding large vesicles, probably helping vesicle extrusion. A putative germ plasm was identified at the 4-cell stage.
Coast-wide recruitment dynamics of Olympia oysters reveal limited synchrony and multiple predictors of failure.

Recruitment of new propagules into a population can be a critical determinant of adult density. We examined recruitment dynamics in the Olympia oyster (Ostrea lurida), a species occurring almost entirely in estuaries. We investigated spatial scales of interannual synchrony across 37 sites in eight estuaries along 2,500 km of Pacific North American coastline, predicting that high vs. low recruitment years would coincide among neighboring estuaries due to shared exposure to regional oceanographic factors. Such synchrony in recruitment has been found for many marine species and some migratory estuarine species, but has never been examined across estuaries in a species that can complete its entire life cycle within the same estuary. To inform ongoing restoration efforts for Olympia oysters, which have declined in abundance in many estuaries, we also investigated predictors of recruitment failure. We found striking contrasts in absolute recruitment rate and frequency of recruitment failure among sites, estuaries, and years. Although we found a positive relationship between upwelling and recruitment, there was little evidence of synchrony in recruitment among estuaries along the coast, and only limited synchrony of sites within estuaries, suggesting recruitment rates are affected more strongly by local dynamics within estuaries than by regional oceanographic factors operating at scales encompassing multiple estuaries. This highlights the importance of local wetland and watershed management for the demography of oysters, and perhaps other species that can complete their entire life cycle within estuaries. Estuaries with more homogeneous environmental conditions had greater synchrony among sites, and this led to the potential for estuary-wide failure when all sites had no recruitment in the same year. Environmental heterogeneity within estuaries may thus buffer against estuary-wide recruitment failure, analogous to the portfolio effect for diversity. Recruitment failure was correlated with lower summer water temperature, higher winter salinity, and shorter residence time: all indicators of stronger marine influence on estuaries. Recruitment failure was also more common in estuaries with limited networks of nearby adult oysters. Large existing oyster networks are thus of high conservation value, while estuaries that lack them would benefit from restoration efforts to increase the extent and connectivity of sites supporting oysters.
Early versus delayed initiation of continuous distending pressure for respiratory distress syndrome in preterm infants.

BACKGROUND The application of a continuous distending pressure (CDP) has been shown to have some benefits in the treatment of pre-term infants with respiratory distress syndrome (RDS). CDP has the potential to reduce lung damage, particularly if applied early before atelectasis has occurred. Early application of CDP may better conserve an infant's own surfactant stores and consequently be more effective than CDP applied later in the course of RDS. OBJECTIVES In pre-term infants with RDS to determine if early compared with delayed initiation of CDP results in lower mortality and reduced need for intermittent positive pressure ventilation. SEARCH STRATEGY The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register (Issue 1, 2002), MEDLINE (1966-2001), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal hand searching mainly in the English language. SELECTION CRITERIA Trials among pre-term infants with respiratory distress syndrome spontaneously breathing at trial entry, which used random or quasi-random allocation to either early or delayed CDP. DATA COLLECTION AND ANALYSIS Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used, including independent assessment of trial quality and extraction of data by two authors. MAIN RESULTS In six studies on a total of 165 infants, early CDP was associated with a significant reduction in subsequent use of intermittent positive pressure ventilation, typical RR 0.55, RD -0.16, NNT 6, but there was no evidence of effect on overall mortality. There was no evidence of effect on the rates of pneumothorax (five studies) or bronchopulmonary dysplasia (one study). Early CDP resulted in a reduction in duration of oxygen therapy in the single study reporting this outcome. REVIEWER'S CONCLUSIONS Early application of CDP has a clinical benefit in the treatment of RDS in that it reduces subsequent use of IPPV and thus may be useful in preventing the adverse effects of this treatment. However, many of the trials were done in the 1970s and 1980s and re-evaluation of the strategy of early CDP in the era of antenatal steroid use and early surfactant administration is indicated.
Distinct Responses in Ammonia-Oxidizing Archaea and Bacteria after Addition of Biosolids to an Agricultural Soil

ABSTRACT The recently discovered ammonia-oxidizing archaea (AOA) have been suggested as contributors to the first step of nitrification in terrestrial ecosystems, a role that was previously assigned exclusively to ammonia-oxidizing bacteria (AOB). The current study assessed the effects of agricultural management, specifically amendment of soil with biosolids or synthetic fertilizer, on nitrification rates and copy numbers of archaeal and bacterial ammonia monooxygenase (amoA) genes. Anaerobically digested biosolids or synthetic fertilizer was applied annually for three consecutive years to field plots used for corn production. Biosolids were applied at two loading rates, a typical agronomic rate (27 Mg hectare−1 year−1) and double the agronomic rate (54 Mg hectare−1 year−1), while synthetic fertilizer was applied at an agronomic rate typical for the region (291 kg N hectare−1 year−1). Both biosolids amendments and synthetic fertilizer increased soil N and corn yield, but only the biosolids amendments resulted in significant increases in nitrification rates and increases in the copy numbers of archaeal and bacterial amoA genes. In addition, only archaeal amoA gene copy numbers increased in response to biosolids applied at the typical agronomic rate and showed a significant correlation with nitrification rates. Finally, copy numbers of archaeal amoA genes were significantly higher than copy numbers of bacterial amoA genes for all treatments. These results implicate AOA as being primarily responsible for the increased nitrification observed in an agricultural soil amended with biosolids. These results also support the hypothesis that physiological differences between AOA and AOB may enable them to occupy distinct ecological niches.
The Effect of Market Orientation on Performance of Sharing Economy Business: Focusing on Marketing Innovation and Sustainable Competitive Advantage

This study investigated relationships among the market orientation of sharing economy business, marketing innovation, sustainable competitive advantage (SCA), and performance. Attempts are made to understand market orientation from cultural and behavioral perspectives to accelerate marketing innovation and identify measures for SCA and performance building. Frequency, reliability, validity, fitness, and path analyses were performed on 400 respondents, and a structural model was used. The results are as follows. First, functional coordination of the cultural market orientation of sharing economy business with consumer orientation significantly affected product innovation, but competitive orientation’s effect on product innovation was not significant. Competitive orientation and functional coordination significantly affected communication innovation, but consumer orientation’s effect on communication innovation was not significant. Second, market information generation and response to market information of behavioral market orientation of sharing economy business significantly influenced product innovation, but market information exchange’s influence on product innovation was not significant. Even though market information exchange and response to market information had a significant influence on communication innovation, the influence of market information generation on communication innovation was not significant. Third, both product and communication innovation of the marketing innovation of sharing economy business significantly influenced SCA. Fourth, the SCA of sharing economy business significantly influenced market dominating power.
Syntheses, opioid binding affinities, and potencies of dynorphin A analogues substituted in positions, 1, 6, 7, 8 and 10.

Structural, stereochemical, stereoelectronic and conformational requirements for biological activity of dynorphin A1-11-NH2 analogues at opioid receptors were explored by substitution of Tyr1, Arg6, Arg7, Ile8 and Pro10 with other amino acid residues. Interestingly, substitution of Tyr1 with N alpha-Ac-Tyr1, D-Tyr1, Phe1 or p-BrPhe1 led to analogues that were quite potent at kappa opioid receptors, and additional substitution of Ile8 with D-Ala8 and/or Pro10 with D-Pro10 retained high potency in brain binding assay: [N alpha-Ac-Tyr1]- (1), [D-Tyr1]-(2) [Phe1]- (3), [Phe1,D-Ala8]- (5), [-BrPhe1, D-Ala8]- (6), [Phe1, D-Pro10]- (7) and [Phe1,D-Ala8, D-Pro10]- Dyn A1-11-NH2 (8) had IC50 (nM) binding affinities of 13.2, 18.6, 1.64, 1.26, 1.84, 2.44 and 1.62 nM, respectively. The D-Phe1 analogue 4, however, was only weakly active (610 nM). All of the analogues except 4 were modestly selective for kappa vs. mu guinea pig brain opioid receptor (11- to 88-fold) and quite selective for kappa vs. delta receptors (65-576). However, all of the analogues appeared to have very low or essentially no activity in the guinea pig ileum and mouse vas deference functional bioassays, and one analogue, 5, appeared to have weak antagonist activities. On the other hand, if constrained amino acids such as beta-methylphenylalanine or 1,2,3,4-tetrahydroisoquinoline carboxylic acid, and hydroxyproline were placed in the 1 position, inactive analogues or analogues with greatly reduced potency and biological activity were obtained (compounds 12-14). It had previously been suggested that the Arg6 and Arg7 residues were critical for biological activity. (ABSTRACT TRUNCATED AT 250 WORDS)