Miracle-dz/UniFAR-FTUs huggingface dataset:
A Reference Laboratory Experience of Clinically Achievable Voriconazole, Posaconazole, and Itraconazole Concentrations within the Bloodstream and Cerebral Spinal Fluid

ABSTRACT Interest in antifungal therapeutic-drug monitoring has increased due to studies demonstrating associations between concentrations and outcomes. We reviewed the antifungal drug concentration database at our institution to gain a better understanding of achievable triazole drug levels. Antifungal concentrations were measured by high-performance liquid chromatography (HPLC), ultraperformance liquid chromatography and single-quadrupole mass spectrometry (UPLC/MS), or a bioassay. For this study, only confirmed human bloodstream (serum or plasma) and cerebral spinal fluid (CSF) concentrations of voriconazole, posaconazole, and itraconazole were analyzed. The largest numbers of bloodstream and CSF samples were found for voriconazole (14,370 and 173, respectively). Voriconazole bloodstream concentrations within the range of 1 to 5.5 μg/ml represented 50.6% of samples. Levels below the lower limit of quantification (0.2 μg/ml) were observed in 14.6% of samples, and 10.4% of samples had levels of ≥5.5 μg/ml. CSF voriconazole levels ranged from undetectable to 15.3 μg/ml and were <0.2 μg/ml in 11% of samples. Posaconazole bloodstream concentrations were ≥0.7 and ≥1.25 μg/ml in 41.6% and 18.9% of samples, respectively. Posaconazole was detected in only 4 of 22 CSF samples (undetectable to 0.56 μg/ml). Itraconazole levels, as measured by UPLC/MS, were ≥0.5 μg/ml in 43.3% and were undetectable in 33.9% of bloodstream samples. In contrast, when measured by a bioassay, itraconazole/hydroxyitraconazole bloodstream concentrations were ≥1.0 μg/ml in 72.9% of samples and were undetectable in 18% of samples. These results indicate that there is marked variability in bloodstream concentrations achieved with these three azoles. In addition, many levels within the bloodstream for each azole and for voriconazole and posaconazole in the CSF were undetectable or below thresholds associated with efficacy.
Release from output interference in recognition memory: A test of the attention hypothesis

Retrieval results in both costs and benefits to episodic memory. Output interference (OI) refers to the finding that episodic memory accuracy decreases with increasing test trials. Release from OI is the restoration of original accuracy at some point during the test. For example, a release from OI in recognition memory testing occurs when the semantic similarity between stimuli decreases midway through testing, suggesting that item representations stored on early trials cause interference on tests occurring on later trials to the extent that the earlier items share features with the latter items. In two recognition memory experiments, we demonstrate release from OI for words and faces. We also test whether release from OI is the result of interference or is due to a boost in attention caused by reorienting to a novel stimulus type. A test for the foils presented during the initial test list supports the interference account of OI. Implications for models of memory are discussed.
Conformational changes in the bacterial SRP receptor FtsY upon binding of guanine nucleotides and SRP.

In cotranslational preprotein targeting in Escherichia coli, the signal recognition particle (SRP) binds to the signal peptide emerging from the ribosome and, subsequently, interacts with the signal recognition particle receptor, FtsY, at the plasma membrane. Both FtsY and the protein moiety of the signal recognition particle, Ffh, are GTPases, and GTP is required for the formation of the SRP-FtsY complex. We have studied the binding of GTP/GDP to FtsY as well as the SRP-FtsY complex formation by monitoring the fluorescence of tryptophan 343 in the I box of mutant FtsY. Thermodynamic and kinetic parameters of the FtsY complexes with GDP, GTP, and signal recognition particle are reported. Upon SRP-FtsY complex formation in the presence of GTP, the fluorescence of tryptophan 343 increased by 50 % and was blue-shifted by 10 nm. We conclude that GTP-dependent SRP-FtsY complex formation leads to an extensive conformational change in the I box insertion in the effector region of FtsY.
Improved sauerkraut production with probiotic strain Lactobacillus plantarum L4 and Leuconostoc mesenteroides LMG 7954.

UNLABELLED Probiotic strain Lactobacillus plantarum L4 and strain Leuconostoc mesenteroides LMG 7954 were applied for the controlled fermentation of cabbage heads. The parameters of the controlled and spontaneous fermentations, including antimicrobial effect of cabbage brines obtained at the end of both fermentations, were monitored. To check out the influence of starter culture strains, 10 randomly chosen lactic acid bacteria, isolated at the end of controlled cabbage heads fermentation were identified by API 50 CHL test, and the presence of the probiotic culture was confirmed by Pulsed Field Gel Electrophoresis. The starter cultures applied for cabbage heads fermentation allowed lowering of NaCl concentrations from 4.0% to 2.5% (w/v), considerably accelerated fermentation process by 14 d, and improved the product quality. The produced sauerkraut heads are considered probiotic product as viable probiotic cells count in final product was higher than 10(6) colony-forming units (CFU) per gram of product. PRACTICAL APPLICATION The results of this research could be applied in the production of fermented cabbage heads with added functional (probiotic) value and with lower NaCl concentration with expected shortened fermentation time. This could not only be of economic but also of ecological importance.
Research on improvement of ac sampling frequency through soft simulation interpolation

Based on the full consideration of the practical demand of power network, this paper proposes the new calculation method of soft simulation interpolation, improved AC sampling frequency the sampling accuracy, which provides a strong technical support for the security and stability of the system operation. Eliminating the abnormal points of intelligent substation integrated energy collection of comprehensively enhance the accuracy of electrical energy collection, making the integrated power more accurate and reliable. In the wide area measurement of power grid, the frequency measurement algorithm of the transient signal is improved, reduce the measurement error, and the quality of the measured phasor is improved and the precision also improved greatly.
Friendly speech analysis and perception in standard Chinese

Previous analyses on friendly speech were made using dialogues without differentiating their linguistic functions. This paper reports an analysis on declarative and interrogative sentences respectively. Pitch and duration of prosodic words were statistically analyzed and compared concerning factors of their positions and stresses. Based on the acoustic investigation of friendly speech, tonal pitch and prosodic duration distributions were adjusted in synthesis and the synthesized stimuli were subjected to perception test. It was found that: (1) Friendliness of synthesized speech could be achieved via adjusting the perceptually distinctive acoustic parameters; (2) Tonal pitch is the most important cue for better expression of friendliness; (3) Only adjusting duration is no use for expressive friendly speech; (4) Interrogative sentences got higher perceptual results than declarative sentences; (5) A high boundary tone for interrogative sentence was usually used by speakers to express friendly speech.
A Comparative Study of the Nutritive Factors and sensory acceptance of Juices from Selected Nigerian Fruits

The nutritive factors of the juices of three fruits: orange, pineapple and pawpaw were studied and compared using standard methods. Proximate analysis of the samples indicated that the nutritive factors investigated in the three juice samples were significantly different (p≤0.05). Orange juice contained 2.19% and 3.65% more moisture and 11.43% and 38.57% more crude protein than pineapple and pawpaw juices while pineapple juice had 40.16% and 45.08% more ash as well as 4.74% and 19.59% more energy content than the others. However, 40.0% and 65.71% more crude lipid, 22.39% and 14.79% more carbohydrates and 11.11% and 40.74% more crude fibre were observed in the pawpaw juice than orange and pineapple juices, respectively. The minerals and vitamin C content of the juices revealed that orange juice had 75.47% and 58.49% more Ca2+ and 31.42% and 11.33% more vitamin C than pineapple and pawpaw juices while pineapple juice had 16.67% more Mg2+ than orange and pineapple juices. Similarly, sensory evaluation showed a significant difference (p≤0.05) in taste, aroma and general acceptability of the juice samples whereas no significant difference (p≤0.05) was observed in the colour of the juice samples. Overall, pineapple juice had 4.82% and 21.69% more preference rating than orange and pawpaw juice samples.
'Surprise': Outbreak of Campylobacter infection associated with chicken liver pâté at a surprise birthday party, Adelaide, Australia, 2012.

OBJECTIVE In July 2012, an outbreak of Campylobacter infection was investigated by the South Australian Communicable Disease Control Branch and Food Policy and Programs Branch. The initial notification identified illness at a surprise birthday party held at a restaurant on 14 July 2012. The objective of the investigation was to identify the potential source of infection and institute appropriate intervention strategies to prevent further illness. METHODS A guest list was obtained and a retrospective cohort study undertaken. A combination of paper-based and telephone questionnaires were used to collect exposure and outcome information. An environmental investigation was conducted by Food Policy and Programs Branch at the implicated premises. RESULTS All 57 guests completed the questionnaire (100% response rate), and 15 met the case definition. Analysis showed a significant association between illness and consumption of chicken liver pâté (relative risk: 16.7, 95% confidence interval: 2.4-118.6). No other food or beverage served at the party was associated with illness. Three guests submitted stool samples; all were positive for Campylobacter. The environmental investigation identified that the cooking process used in the preparation of chicken liver pâté may have been inconsistent, resulting in some portions not cooked adequately to inactivate potential Campylobacter contamination. DISCUSSION Chicken liver products are a known source of Campylobacter infection; therefore, education of food handlers remains a high priority. To better identify outbreaks among the large number of Campylobacter notifications, routine typing of Campylobacter isolates is recommended.
To be kind or not to be kind: The moderating role of self-compassion in the relationship between general resourcefulness and academic self-regulation

ABSTRACT We investigated whether the relationship between students’ general resourcefulness and academic self-regulation changes as a function of self-compassion. A predominantly female sample of 196 undergraduates completed inventories assessing these and other measures. The significant moderating effect of self-compassion revealed that the positive relationship between general resourcefulness and academic self-regulation was stronger for participants scoring low in self-compassion than high in self-compassion. For those low in self-compassion, scoring low in general resourcefulness was associated with the lowest academic self-regulation, whereas scoring high in general resourcefulness was associated with the greatest academic self-regulation. The positive relationship between general and academic self-regulation was attenuated for participants high in self-compassion, with predicted scores for academic self-regulation falling in between the two values described for the low self-compassion function. Implications of the findings are discussed, including the potential value of incorporating self-compassion training alongside programs aimed at increasing general resourcefulness and academic self-regulation.
SOX 4 is a direct target gene of FRA-2 and induces expression of HDAC 8 in adult T-cell leukemia / lymphoma

• SOX4 is consistently expressed in ATL, is involved in ATL cell growth, and induces genes such as GCRK, NAP1, and HDAC8 in ATL. • FRA-2/JUND and SOX4 form an important oncogenic cascade in ATL, leading to upregulation of genes such as HDAC8. Previously, wehaveshown that anAP-1 familymember,FRA-2, is constitutively expressed in adult T-cell leukemia/lymphoma (ATL) and, together with JUND, upregulates CCR4 and promotesATLcell growth. Among the identified potential target genes of FRA-2/JUNDwas SOX4. Here, we examine the expression and function of SOX4 in ATL. SOX4 was indeed consistently expressed in primary ATL cells. FRA-2/JUND efficiently activated the SOX4 promoter via an AP-1 site. Knockdown of SOX4 expression by small interfering RNA (siRNA) strongly suppressed cell growth of ATL cell lines. Microarray analyses revealed that SOX4 knockdown reduced the expression of genes such as germinal center kinase related (GCKR), NAK-associated protein 1 (NAP1), and histone deacetylase 8 (HDAC8). We confirmed consistent expression of GCKR, NAP1, and HDAC8 in primary ATL cells. We also showed direct activation of the HDAC8 promoter by SOX4. Furthermore, siRNA knockdown ofGCKR,NAP1, andHDAC8 each significantly suppressed cell growth of ATL cell lines. Taken together, we have revealed an important oncogenic cascade involving FRA-2/JUND and SOX4 in ATL, which leads to the expression of genes such as GCKR, NAP1, and HDAC8. (Blood. 2013;121(18):3640-3649)
TOPOLOGICAL AND MOTION STRATEGIES FOR CELLULAR MEMETIC TREE-BASED PORTFOLIO OPTIMIZATION

Portfolio Optimization (PO) is a resource allocation problem where real valued weights are assigned to multiple financial assets in order to maximize the return and minimize the risk. The Memetic Tree-based Algorithm (MTGA), employing a tree representation allied with local search (LS) has shown great performance compared to other weight balancing techniques. In this work, we hybridize MTGA with topological frameworks — Cellular Memetic Algorithms (CMA) — and study four implementations, varying whether the individuals move through the grid, and whether meta-parameters are spread along the axes for self-adaptation. The approaches are compared using a historical data simulation. A CMA which incorporates motion performs best, while parameter tuning was less successful. The results not only describe an improved method for PO, but also have broader implications for cellular models wherein the benefits of motion are shown to deserve further investigation.
Inhibition of α7‐containing nicotinic ACh receptors by muscarinic M1 ACh receptors in rat hippocampal CA1 interneurones in slices

Cys‐loop ligand‐gated nicotinic ACh receptors (nAChRs) and G protein‐coupled muscarinic ACh receptors (mAChRs) are expressed on rat hippocampal interneurones where they can regulate excitability, synaptic communication and cognitive function. Even though both nAChRs and mAChRs appear to co‐localize to the same interneurones, it is not clear whether there is crosstalk between them. We utilized patch‐clamp techniques to investigate this issue in rat hippocampal CA1 interneurones in slices under conditions where synaptic transmission was blocked. The α7 nAChR‐mediated currents were activated by choline, and when the activation of this receptor was preceded by the activation of the M1 mAChR subtype, the amplitude of α7 responses was significantly reduced in a rapidly reversible and voltage‐independent manner, without any change in the kinetics of responses. This M1 mAChR‐mediated inhibition of α7 nAChRs was through a PLC‐, calcium‐ and PKC‐dependent signal transduction cascade. These data show that M1 mAChRs and α7 nAChRs are functionally co‐localized on individual rat hippocampal interneurones where the activation of these particular mAChRs inhibits α7 nAChR function. This information will help to understand how these cholinergic receptor systems might be regulating neuronal excitability in the hippocampus in a manner that has relevance for synaptic plasticity and cognition.
Longitudinal evaluation of the occurrence of MRI-detectable bone marrow edema in osteoarthritis of the knee

Background: Bone marrow edema (BME) is a condition detectable with magnetic resonance imaging (MRI) and is present in different stages of osteoarthritis (OA). Its pathogenesis is still not completely known. Purpose: To evaluate the longitudinal occurrence and persistence of BME in early OA of the knee. Material and Methods: Twenty-three patients (eight females, 15 males; mean age 55.5±10.3 years) were scanned with a 1.5T MR imaging unit (sagittal fat-suppressed intermediate-weighted fast spin echo; 4-mm section thickness, 1-mm intersection gap, 256x192 matrix, 120-mm field of view). Images were obtained in all 23 patients at two time points (TPs) and in 12 patients at three TPs. Images were evaluated by two readers independently; discrepancies in image grading were reviewed and evaluated in consensus. A four-point image-grading scale was used (absence of BME to severe BME). Four main anatomical regions were evaluated (medial femur, lateral femur, medial tibia, lateral tibia), which were subcategorized into anterior, central, and posterior regions. Results: One hundred five areas of BME in the 23 patients were found at all three TPs. In 16 areas, the BME was consistent at the same location over time, in seven locations the BME became larger, in six areas the BME became smaller, and in 16 locations it could not be detected in follow-up MRIs. In one case, the BME was smaller at TP2 but increased at TP3. In eight cases, only at the last time point could a BME be detected. Conclusion: BME is not a static phenomenon but changes over time. Correlation to physical activity and local inflammatory reaction should be evaluated.
Corticosteroid insensitive alveolar macrophages from asthma patients; synergistic interaction with a p38 mitogen-activated protein kinase (MAPK) inhibitor.

AIMS Some asthma patients remain symptomatic despite using high doses of inhaled corticosteroids (ICS). We used alveolar macrophages to identify individual patients with insensitivity to corticosteroids and to evaluate the anti-inflammatory effects of a p38 mitogen-activated protein kinase (MAPK) inhibitor combined with a corticosteroid on these cells. METHODS Alveolar macrophages from 27 asthma patients (classified according to the Global Initiative for Asthma (GINA) treatment stage. Six GINA1, 10 GINA2 and 11 GINA3/4) were stimulated with lipoploysaccharide (LPS) (1 μg ml(-1)). The effects of dexamethasone (dex 1-1000 nm), the p38 MAPK inhibitor 1-(5-tert-butyl-2-p-tolyl-2Hpyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl)urea (BIRB-796 1-1000 nm) and both drugs combined at all concentrations on supernatant TNFα, IL-6 and CXCL-8 concentrations were analyzed by ELISA. Dose-sparing and efficacy enhancing effects of combination treatment were determined. RESULTS Dexamethasone reduced LPS-induced TNFα, IL-6 and CXCL-8 in all groups, but maximum inhibition was significantly reduced for GINA3/4 compared with GINA2 and GINA1 (P < 0.01). A subgroup of corticosteroid insensitive patients with a reduced effect of dexamethasone on cytokine secretion were identified. BIRB-796 in combination with dexamethasone significantly increased cytokine inhibition compared with either drug alone (P < 0.001) in all groups. This effect was greater in corticosteroid insensitive compared with sensitive patients. There were significant synergistic dose-sparing effects (P < 0.05) for the combination treatment on inhibition of TNFα, IL-6 and CXCL-8 in all groups. There was also significant efficacy enhancing benefits (P < 0.05) on TNFα and IL-6. CONCLUSIONS p38 MAPK inhibitors synergistically enhance efficacy of corticosteroids in macrophages from asthma patients. This effect is greater in corticosteroid insensitive asthma patients, suggesting that this class of drug should be targeted to this patient phenotype.
A lymphohistiocytic variant of anaplastic large cell lymphoma with demonstration of the t(2;5)(p23;q35) chromosome translocation

Cytogenetic investigations were performed in a case of a nodal malignant non‐Hodgkin's lymphoma. Histopathological analysis from an involved lymph node as well as from a skin biopsy revealed a lymphohistiocytic variant of CD30‐positive anaplastic large cell lymphoma (ALCL). A t(2;5)(p23;q35) chromosome translocation could be observed in all metaphases analysed. This finding was confirmed both by RT‐PCR analysis of the NPM/ALK fusion protein and by positive staining with the p80NPM/ALK antibody. To the best of our knowledge, this is the first report of a t(2;5) documented by classic cytogenetics in the lymphohistiocytic variant of ALCL.
Perturbation expansion for particle distributions in hadron storage rings.

Based on the perturbation theory with multiple scales, we have developed a new technique to study the evolution of particle distribution as a function of oscillation amplitudes in hadron storage rings. With a renormalization scheme for the zeroth‐order term, a uniformly valid perturbations such as the beam‐beam interaction at colliding points, this renormalization scheme results in a functional mapping for the particle distribution, and the diffusion processes of particles in the beam can be studied numerically without resorting to the tracking of individual particles. A case involving a single nonliner kick in the ring is presented to illustrate the method in detail.
Metabolism of carbon monoxide by Rhodopseudomonas gelatinosa: cell growth and properties of the oxidation system

Rhodopseudomonas gelatinosa 1 grew as an anaerobic facultative methylotroph with carbon monoxide as the sole carbon and energy source. Carbon from CO was assimilated into cell material via the ribulose 1,5-bisphosphate carboxylase cycle. The CO oxidation system in R. gelatinosa was induced during growth with the gas substrate. Light-grown cells did not oxidize CO. Surprisingly, when strain 1 cells grown in the dark with CO were transferred to growth with both CO and light, they continued to use CO and then photometabolized after the CO gas flow was stopped. This change in the energy-yielding substrate resulted in a diauxic growth response. The use of CO in preference to light energy forms the basis of a system in the cells that controls photosynthetic differentiation. CO oxidation was assayed as CO-methyl viologen oxidoreductase. Methyl viologen reduction only occurred with CO; the dye was not reduced with other C1 compounds. In vitro methyl viologen was reduced best at 24 degrees C and at pH values above 8.5. Whole cells exhibited a Km of 12.5 microM for CO and a Vmax of 3,800 nmol of CO oxidized per mg of protein per min. This was a low-potential oxidation reaction that readily reduced the viologen dye triquat (1,1'-trimethylene-2,2'-dipyridilium dibromide) (E degrees' = -548 mV).