Miracle-dz/UniFAR-FTUs huggingface dataset:
Review: Lipopolysaccharide biosynthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa causes serious nosocomial infections, and an important virulence factor produced by this organism is lipopolysaccharide (LPS). This review summarizes knowledge about biosynthesis of all three structural domains of LPS — lipid A, core oligosaccharide, and O polysaccharides. In addition, based on similarities with other bacterial species, this review proposes new hypothetical pathways for unstudied steps in the biosynthesis of P. aeruginosa LPS. Lipid A biosynthesis is discussed in relation to Escherichia coli and Salmonella, and the biosyntheses of core sugar precursors and core oligosaccharide are summarised. Pseudomonas aeruginosa attaches a Common Polysaccharide Antigen and O-Specific Antigen polysaccharides to lipid A-core. Both forms of O polysaccharide are discussed with respect to their independent synthesis mechanisms. Recent advances in understanding O-polysaccharide biosynthesis since the last major review on this subject, published nearly a decade ago, are highlighted. Since P. aeruginosa O polysaccharides contain unusual sugars, sugar-nucleotide biosynthesis pathways are reviewed in detail. Knowledge derived from detailed studies in the O5, O6 and O11 serotypes is applied to predict biosynthesis pathways of sugars in poorly-studied serotypes, especially O1, O4, and O13/O14. Although further work is required, a full understanding of LPS biosynthesis in P. aeruginosa is almost within reach.
Human pro alpha 1(I) collagen: cDNA sequence for the C-propeptide domain

We have previously constructed a cDNA clone pHCALl, covering most of the Cterminal propeptide domain of human proal(I) collagen mSNA, by inserting a 678 bp EcoRI-XhoI fragment of cDNA into pBR322 (1). Since the Xhol/Sall ligation prevented removal of the insert, we used the same strategy to obtain a similar clone in pUC8. RNA was isolated from fetal calvarial bones. The cDNA was digested with EcoRI and Xhol and fractionated on a 1 X agarose gel. Fragments of 650-700 bp were cloned in pUC8 at the polylinker site, which now permits easy removal of the insert (2). The new clone was named pHCALIU since the RNA was isolated from another individual. Sequencing of pHCALlU by the Sanger dideoxy method filled the two gaps (nucleotides 67 and 487) which remained in the previously published sequence (3). Three base differences were observed (shown above pHCALIU sequence): two of these bordered the missing nucleotide (positions 66 and 68). The third difference (a transversion at nucleotide 616) changes the codon from TCC (ser, ref. 3) to ACC (thr), and may represent individual variation. The corresponding chick sequence also contains ACC (4). The approach outlined here is useful for studies on individual variation which is important to recognize when searching for disease-related mutations in type I collagen.
Screening for postoperative delirium in patients with acute hip fracture: Assessment of predictive factors

The aim of the present study was to estimate the incidence and risk factors of delirium during the early postoperative period after hip fracture surgery. Furthermore, we investigated the accuracy of the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) for detection and assessment of delirium in orthopedic patients.
Cellular Events Involved in Survival of Individual Arbuscular Mycorrhizal Symbionts Growing in the Absence of the Host

ABSTRACT A survival strategy operating in the absence of the host was shown in obligately biotrophic arbuscular mycorrhizal (AM) symbionts. When no host-derived signals from the surrounding environment were perceived by germinating spores, fungal hyphae underwent a programmed growth arrest and resource reallocation, allowing long-term maintenance of viability and host infection capability. The early stages of mycelial growth of AM fungi were studied by a combination of time-lapse and video-enhanced light microscopy, image analysis, and immunodetection, with the aim of acquiring knowledge of cell events leading to the arrest of mycelial growth. The time-course of growth arrest was resolved by precisely timing the growth rate and magnitude of the mycelium originating from individual spores of Glomus caledonium. Extensive mycelial growth was observed during the first 15 days; thereafter, fungal hyphae showed retraction of protoplasm from the tips, with formation of retraction septa separating viable from empty hyphal segments. This active process involved migration of nuclei and cellular organelles and appeared to be functional in the ability of the fungus to survive in the absence of a host. Immunodetection of cytoskeletal proteins, metabolic activity, and the retention of infectivity of germinated spores confirmed the developmental data. The highest amounts of tubulins were detected when hyphal growth had ceased but when retraction of protoplasm was most active. This was consistent with the role of the cytoskeleton during protoplasm retraction. Succinate dehydrogenase activity in hyphae proximal to the mother spore was still detectable in 6-month-old mycelium, which remained viable and able to form appressoria and produce symbiotic structures.
Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin.

The effect of oral controlled-release (CR), oral transmucosal (buccal; TMD) and transdermal (TDD) drug delivery systems on plasma concentrations of melatonin (MT) and its principal metabolite in human subjects using a crossover, single dose design was evaluated. Twelve adult male volunteers participated in the study and received all three dosage forms on three separate occasions. All patch dosage forms were removed after 10 h of wear. Plasma concentrations of the parent drug and its metabolite, 6-sulfatoxymelatonin (MT6s) were measured by radioimmunoassay. Between-subject plasma concentrations of MT were very variable following both oral CR and TDD. Use of the oral CR system gave plasma MT profiles in some subjects that were initially similar to physiological levels, but then differed substantially from physiological in the rate of MT offset; in a few subjects, plasma MT levels remained consistently much below normal nocturnal physiological levels. Also, the ratio of metabolite to parent drug by the oral CR route was many times greater than physiological. TDD resulted in a significant delay in systemic drug levels and a gradual decline in drug delivery after patch removal, possibly due to deposition of melatonin in the skin. TDD failed to simulate the physiological plasma profile of MT (rapid achievement of steady-state blood levels and rapid decline after removal of the patch; i.e., so-called "square-wave" profile). TMD provided prompt systemic drug levels with less variability than oral CR or TDD delivery. Also, plasma MT levels fell promptly and rapidly after removal of the patch. No indication of mucosal deposition was observed. TMD was able to mimic the physiological plasma profiles of both MT and its principal metabolite.
Estimating the transmission parameters of pneumococcal carriage in households

This paper analyses Streptococcus pneumoniae transmission dynamics in households using longitudinal data on pneumococcal (Pnc) carriage in the United Kingdom. Ten consecutive swabs were taken at 4-week intervals from all members of 121 households. The family status is derived from the observed Pnc carriage status of each family member. Transition matrices are built for each family size and composition containing the observed frequency of transitions between family statuses over a 28-day interval. A density-dependent transmission model is fitted to derive maximum-likelihood estimates of the duration of carriage and acquisition rates from the community and from infected individuals within the household. Parameter values are estimated for children (<5 years) and adults (5+ years). The duration of carriage is longer in children <5 years of age than in older family members (51 vs. 19 days). Children are 3–4 times more likely than adults to acquire Pnc infection from the community. Transmission rates within the household suggest that adults are more infectious but less susceptible than children. Transmission within the household is most important in large families. The proportion of household-acquired infection ranges from 29 to 46% in households of three persons to 38–50% in larger households. Evidence of density-dependent within-household transmission is found, although the strength of this relationship is not clear from the model estimates.
Endotoxin induces respiratory failure and increases surfactant turnover and respiration independent of alveolocapillary injury in rats.

Although endotoxin-induced acute lung injury is associated with inflammation, alveolocapillary injury, surfactant dysfunction, and altered lung mechanics, the precise sequence of these changes is polemic. We have studied the early pathogenesis of acute lung injury in spontaneously breathing anesthetized rats after intravenous infusion of Salmonella abortus equi endotoxin. The animals became hypoxic, and airway resistance, tissue resistance, lung elastance, and static compliance all deteriorated well before any change in alveolar neutrophils, macrophages, lung fluid (99mTc-labeled diethylenetriamine pentaacetic acid), or 125I-albumin flux, which were only appreciably increased at 8.5 hours. Lung elastance deteriorated before airway resistance, indicating that the compliance change was specific rather than caused by reduced lung volume. The subcellular and alveolar content of surfactant proteins A and B, cholesterol, disaturated phospholipids, and phospholipid classes remained normal in the face of a dramatic increase in the synthesis and turnover of 3H-disaturated phosphatidylcholine. Our findings indicate that the increase in surfactant disaturated phospholipid turnover reflects, at least in part, an approximately five-fold increase in "sigh frequency. " We suggest that endotoxin has direct effects on tissue resistance and lung elastance independent of surfactant composition and that the initial respiratory failure results primarily from endotoxin-induced ventilation/perfusion mismatch independent of edema or alveolocapillary injury per se.
Dose-dependent effects of a microbial phytase on phosphorus digestibility of common feedstuffs in pigs

Objective The objective of this study was to evaluate increasing doses of a novel microbial phytase (Cibenza Phytaverse, Novus International, St. Charles, MO, USA) on standardized total tract digestibility (STTD) of P in canola meal (CM), corn, corn-derived distiller’s dried grains with solubles (DDGS), rice bran (RB), sorghum, soybean meal (SBM), sunflower meal (SFM), and wheat. Methods Two cohorts of 36 pigs each (initial body weight = 78.5±3.7 kg) were randomly assigned to 2 rooms, each housing 36 pigs, and then allotted to 6 diets with 6 replicates per diet in a randomized complete block design. Test ingredient was the only dietary source of P and diets contained 6 concentrations of phytase (0, 125, 250, 500, 1,000, or 2,000 phytase units [FTU]/kg) with 0.4% of TiO2 as a digestibility marker. Feeding schedule for each ingredient was 5 d acclimation, 5 d fecal collection, and 4 d washout. The STTD of P increased (linear or exponential p≤0.001) with the inclusion of phytase for all ingredients. Results Basal STTD of P was 37.6% for CM, 37.6% for corn, 68.6% for DDGS, 10.3% for RB, 41.2% for sorghum, 36.7% for SBM, 26.2% for SFM, and 55.1% for wheat. The efficiency of this novel phytase to hydrolyze phytate is best described with a broken-line model for corn, an exponential model for CM, RB, SBM, SFM, and wheat, and a linear model for DDGS and sorghum. Based on best-fit model the phytase dose (FTU/kg) needed for highest STTD of P (%), respectively, was 735 for 64.3% in CM, 550 for 69.4% in corn, 160 for 55.5% in SBM, 1,219 for 57.8% in SFM, and 881 for 64.0% in wheat, whereas a maximum response was not obtained for sorghum, DDGS and RB within the evaluated phytase range of 0 to 2,000 FTU/kg. These differences in the phytase concentration needed to maximize the STTD of P clearly indicate that the enzyme does not have the same hydrolysis efficiency among the evaluated ingredients. Conclusion Variations in enzyme efficacy to release P from phytate in various feedstuffs need to be taken into consideration when determining the matrix value for phytase in a mixed diet, which likely depends on the type and inclusion concentration of ingredients used in mixed diets for pigs. The use of a fixed P matrix value across different diet types for a given phytase concentration is discouraged as it may result in inaccurate diet formulation.
Government expenditure and growth in Libya.

This study attempts to answer two main questions. First, how does the composition of public expenditure affect the economic growth rate of macroeconomic variables such as the real output of the non-oil sector, employment, and total imports in Libya? Second, what is the appropriate fiscal and/or monetary policy to be used by the Libyan government to finance public expenditure, especially after the collapse in the oil price in the 1990s? To achieve these ends, a small macro-econometric model of the Libyan economy is constructed for the period 1962-1992 and estimated using the Johansen approach. The model reflects the Libyan institutional environment relevant to the observation period. The model links public finances to the monetary sector, the real sector, the role of foreign trade and the balance of payments, and the labour market. The model is utilised to (1) examine the impact of government expenditure on the growth of the macro-economic variables mentioned above; (2) examine the impact of different ways of funding these expenditures; (3) examine long-run equilibrium relationships estimated through the cointegration approach. The short-run dynamics was modelled via error correction models. Evaluation of the model was through standard single equation diagnostics, model simulation, and forecasting. Policy simulation was used to evaluate macro-economic policy options open to the government of Libya. As a result this study provides considerable knowledge about the structure of the Libyan economy through the period 1962-1992, and about the impact of government expenditure and its finance instrument (fiscal and/or monetary means) on growth.
Image analysis of neutrophil nuclear morphology: Learning about phenotypic range and its reliable analysis from patients with pelger‐Huët‐anomaly and treated with colchicine

The nuclear morphology of neutrophils depends on different endogenous and exogenous factors, which can lead to hypo‐ or hypersegmentation of the normally 2–4 segmented nucleus. Hyposegmentation can be due to mutations in the LBR‐gene (Pelger‐Huët‐Anomaly) or can be induced, for example, by colchicine treatment. The range of this phenotypic variation is known as “norm of reaction,” which can be of major relevance for clinical diagnosis and therapeutic intervention. In this project, we studied the norm of reaction in 26 subjects with 0–3 wild type LBR alleles. In addition, the phenotypic variation was analyzed in 3 patients with Familial Mediterranean Fever (FMF), before and after colchicine treatment. We measured the phenotype nuclear segmentation of neutrophils based on two conventional qualitative methods, the “rule of threads” and the “rule of thirds. ” In addition, we tested a morphometric quantitative approach, the “circularity index. ” The circularity index was superior in cases with hyposegmentation; the rule of thirds with respect to hypersegmentation. Approximately 65% of the observed phenotypic variance was explainable by the number of LBR wild type alleles. The gene‐dosage effect followed a non‐additive, hysteresis‐like characteristic with lower and upper plateaus. Colchicine treatment had a clear, although minor phenotypic effect compared to the number of LBR wild type genes or the mutation type. Thus, the nuclear morphology of granulocytes and its norm of reaction can be regarded as an excellent model both for detailing the interplay between endogenous and exogenous factors and for clinical diagnostic purposes. © 2016 International Clinical Cytometry Society
Modeling and simulation of complex heterogeneous systems

Given the increasing heterogeneity and complexity of systems being developed, untimed modeling at a system level becomes more and more important for design space exploration and verification, due to its conciseness and speed. After showing inadequacies of SystemC, which is the predominant modeling environment in this area, we propose a paradigm shift from immediate notifications and coroutines in SystemC to Atomic Actions and true parallelism in an extension of Esys.NET. We exploit the introspection and attribute programming to extend the capabilities of the environment and to build the basis for heterogeneous cosimulation. This paper aims to show the main advantages of this paradigm shift, such as (1) the improvement of simulation time by exploiting the capabilities of multicore simulation hosts, (2) the reduction of modeling hazards related to parallelism and resource sharing, and (3) a more efficient design space exploration.
The “Toilet Circuit”: Cultural Production, Fandom and Heritage in England's Small Music Venues

Abstract In its broadest sense, the Toilet Circuit comprises smaller and independent music venues in the UK that launched many now famous artists and bands, alongside supporting many that are locally known, igniting or sustaining all-important local music scenes and their cultural production. Fueled by alcohol, drugs and adrenalin, the turbulent atmosphere of Toilet Circuit venues offer escapism for disaffected youth within the seedy aesthetic environment evocative of a recalcitrant culture. These raucous grime-pits play a vital role in the ecology of Britain's music scene and broader cultural sector. Against a backdrop of closures, this paper seeks to explore the significance of these venues and their future, using three iconic examples in London, Leeds and Kent.
The mechanism of Drosophila leg development along the proximodistal axis

During development of higher organisms, most patterning events occur in growing tissues. Thus, unraveling the mechanism of how growing tissues are patterned into final morphologies has been an essential subject of developmental biology. Limb or appendage development in both vertebrates and invertebrates has attracted great attention from many researchers for a long time, because they involve almost all developmental processes required for tissue patterning, such as generation of the positional information by morphogen, subdivision of the tissue into distinct parts according to the positional information, localized cell growth and proliferation, and control of adhesivity, movement and shape changes of cells. The Drosophila leg development is a good model system, upon which a substantial amount of knowledge has been accumulated. In this review, the current understanding of the mechanism of Drosophila leg development is described.
3-D Silicon Integration and Silicon Packaging Technology Using Silicon Through-Vias

System-on-Chip (SOC) and System-on-Package (SOP) technologies each have advantages depending on application needs. As system architects and designers leverage ever-increasing CMOS technology densities, a range of two- and three-dimensional silicon integration technologies are emerging which will likely support next-generation high-volume electronic applications and may serve high-performance computing applications. This paper will discuss a few emerging technologies which offer opportunities for enhanced circuit performance, or reduced power as one example. Silicon-on-silicon integration may include three-dimensional (3-D) integration on-chip or may leverage chip stacking or chip integration on package. Common technology features include silicon through-vias, high-I/O interconnection and silicon-on-silicon either as 3-D integrated circuits, integrated chip stacks or silicon-on-silicon packages with passive function or high-bandwidth wiring. Silicon chips on silicon interposers with integrated function such as decoupling capacitors may provide a better module architecture compared to increased on-chip decoupling or off chip discrete capacitors mounted on package at the chip perimeter or underside of the package. Advanced silicon carrier package technology with fine pitch (50 mum) interconnection is described. This silicon carrier package contains silicon through-vias and offers >16times increase over standard chip I/O, a 20times to 100times increase in wiring density over traditional organic and ceramic packaging, and allows for integrated high-performance passives. Silicon carrier technology supports lithographic scaling and provides a basis for known good die (KGD) wafer testing. It may be considered for use in a number of applications including optoelectronic (OE) transceivers, silicon interposers with integrated decoupling capacitors, and mini-multi-chip modules (MMCMs) which integrate heterogeneous dies forming a single "virtual chip. "
Pharmacokinetics of a testosterone gel in healthy postmenopausal women.

BACKGROUND The paucity of pharmacokinetic data on androgen formulations in women has hindered clinical trials of testosterone supplementation in women. OBJECTIVE The objective of this study was to determine the time course and profile of serum testosterone concentrations during treatment with different doses of testosterone gel in postmenopausal women and assess whether estrogen treatment affects the pharmacokinetics of testosterone gel. METHODS Postmenopausal women with total testosterone levels less than 33 ng/dl after baseline 24-h sampling were treated with 4.4, 8.8, or 13.2 mg testosterone gel daily for 7 d each in random order, with a 7-d washout period between doses. We studied 13 women who had not received estrogen therapy (group I) and 13 who had received stable estrogen therapy for 3 months or more (group II). Total and free testosterone concentrations were measured for 48 h on the seventh day of each dose administration. RESULTS Twenty-six women were randomized; of these, 24 were evaluable, 13 in group I and 11 in group II. The average steady-state concentrations (Cav) of serum total and free testosterone increased with increasing testosterone dose and were highly correlated with the dose (dose effect, P < 0.00001), but were not affected by estrogen therapy (P = 0.43). In both groups, the 4.4-mg dose increased Cav total and free testosterone into the mid- to high-normal range, whereas 8.8- and 13.2-mg doses raised total (Cav: 22.3, 51.6, 80.3, and 92.0 ng/dl in group I; 22.7, 59.8, 82.0, and 114.3 ng/dl in group II at 0, 4.4, 8.8, and 13. 2 mg, respectively) and free testosterone (5.9, 8.4, 11.5,12.8 pg/ml in group I and 5.0,7.6,11.1,10.8 in group II, respectively, at the various doses) above the physiological range. The area under the curve, maximum and minimum concentrations, and the change in Cav for total and free testosterone were dose related and significantly higher during administration of the 13.2-mg dose than during the 0- or 4.4-mg dose; estrogen therapy had no significant effect on these measures. Serum estradiol, LH, FSH, and SHBG levels did not change significantly at any dose. Testosterone gel was well tolerated. CONCLUSIONS Administration of testosterone gel to postmenopausal women raised total and free testosterone concentrations in proportion to the administered dose without affecting estradiol levels. A 4.4-mg dose raised testosterone levels into the mid- to high-normal range. Previous estrogen therapy had no significant effect on testosterone pharmacokinetics over this short duration.