Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystals of monosodium urate monohydrate enhance lipopolysaccharide-induced release of interleukin 1β by mononuclear cells through a caspase 1-mediated process

Objective: Recent studies suggest that crystals of monosodium urate (MSU), deposited in joints of patients with acute gouty arthritis, activate the NACHT domain, leucine-rich repeat and pyrin domain-containing protein (NALP)3 inflammasome. In the present study we have investigated whether production of proinflammatory cytokines by crystals was exacerbated during costimulation with Toll-like receptor (TLR) ligands. Methods: Mononuclear cells of 22 healthy donors were stimulated by various concentrations of MSU crystals in the absence or presence of lipopolysaccharide (LPS), Pam3Cys and flagellin. Production of tumour necrosis factor α (TNFα), interleukin (IL)1β and IL6, as well as the intracellular concentrations of proIL1β were measured by ELISA. mRNA transcripts of TNFα and IL1β were assessed by real-time PCR. Stimulation experiments were also performed with peripheral blood mononuclear cells (PBMCs) of one patient carrying a NALP3 mutation. Results: MSU induced a moderate release of IL1β and IL6, but not of TNFα. Urate crystals amplified IL1β production stimulated by the TLR4 ligand LPS, while no synergy was apparent for IL6 production. In addition, no synergy between urate crystals and Pam3Cys (TLR2 ligand) or flagellin (TLR5 ligand) was apparent. The synergy between urate crystals and LPS was directed at the level of the NALP3 inflammasome, as it was present only when active IL1β was measured, but not at the level of IL1 mRNA or proIL1β. The synergy between LPS and MSU crystals ceased to exist in the presence of a caspase 1 inhibitor. Conclusions: MSU crystals act in synergy with LPS for the induction of enhanced release of IL1β. Increased cleavage of proIL1β by urate-activated caspase 1 is proposed as the underlying mechanism.
Characterizing microscale biological samples under tensile loading: stress-strain behavior of cell wall fragment of onion outer epidermis.

UNLABELLED PREMISE OF THE STUDY The results of published studies investigating the tissue-scale mechanical properties of plant cell walls are confounded by the unknown contributions of the middle lamella and the shape and size of each cell. However, due to their microscale size, cell walls have not yet been characterized at the wall fragment level under tensile loading. It is imperative to understand the stress-strain behavior of cell wall fragments to relate the wall's mechanical properties to its architecture. • METHODS This study reports a novel method used to characterize wall fragments under tensile loading. Cell wall fragments from onion outer epidermal peels were cut to the desired size (15 × 5 µm) using the focused ion beam milling technique, and these fragments were manipulated onto a microelectromechanical system (MEMS) tensile testing device. The stress-strain behavior of the wall fragments both in the major and minor growth directions were characterized in vacuo. • KEY RESULTS The measured mean modulus, fracture strength, and fracture strain in the major growth direction were 3.7 ± 0.8 GPa, 95.5 ± 24.1 MPa, and 3.0 ± 0.5%, respectively. The corresponding properties along the minor growth direction were 4.9 ± 1.2 GPa, 159 ± 48.4 MPa, and 3.8 ± 0.5%, respectively. • CONCLUSIONS The fracture strength and fracture strain were significantly different along the major and minor growth directions, the wall fragment level modulus of elasticity anisotropy for a dehydrated cell wall was 1.23, suggesting a limited anisotropy of the cell wall itself compared with tissue-scale results.
Using debriefing and feedback in simulation to improve participant performance: an educator’s perspective

As a clinical skills educator I am involved in the delivery of simulation based education for UK trained doctors in their first year post qualifying (Foundation Year 1 [FY1]). I have an interest in the use of feedback and debrief as a tool to improve performance through reflection. When relating simulation to Kolb’s1 learning cycle it is evident that taking part in the simulated scenario only accounts for the concrete experience component. Debrief and feedback accounts for the reflective observation, abstract conceptualization and active experimentation components of the learning cycle by helping participants make sense of the simulation scenario and reflect on their practice to improve future performance.
Development of the Lateral Line System in the Shovelnose Sturgeon

The lateral line systems of aquatic amphibians and all chondrichthyan and osteichthyan fish present a similar array of mechanoreceptors. However, electroreceptors, the second major component of the lateral line system, have clearly undergone more significant evolutionary change. Chondrichthyans and non-neopterygian fish possess primitive ampullary organ electroreceptors, whereas significantly different ‘new’ ampullary organs and tuberous electroreceptors are found in a few groups of teleosts (mormyrids, gymnotids and some catfish). The pairing of mechano- and electroreceptors in the lateral line system, as well as the morphologically and physiologically distinct electroreceptors of teleosts have inspired several recent studies on the origin and evolution of the lateral line receptors. We described the development of the lateral line system in sturgeon (Scaphirhynchus platorynchus) as part of an outgroup analysis of lateral line development in three taxa: vertebrates that have both mechanoreceptive neuromasts and primitive electroreceptors; neopterygian fish that only have mechanoreceptors; and teleosts that have re-evolved new electroreceptors. Development in Scaphirhynchus was consistent with previously studied taxa in that the lateral line system developed from a series of six dorsolateral placodes. Interestingly, we found that the octaval placode was bound rostrally and caudally by large placodal fields, out of which the six lateral line placodes arose. This finding supports recent suggestions for a common placodal primordium for all placodes. Each of the six placodes gave rise to the lateral line nerves before elongating into sensory ridges, which contained neuromast primordia. The ampullary organ fields of Scaphirhynchus arose from the lateral zones of the anterodorsal, anteroventral, otic and supratemporal sensory ridges, which is also consistent with recently studied taxa. Comparisons of the lateral line system of Scaphirhynchus and close relatives, Acipenser and Polyodon, indicate that variation in some aspects of lateral line receptor numbers and distribution are related to changes in head morphology and feeding strategy, whereas other changes, such as a reduction in receptor number without a change in placode field size, indicate changes in placode development.
The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes

Postprandially, the blood flow and uptake of non‐esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin‐resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age‐ and weight‐matched healthy subjects were studied. Contrast‐enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75‐g oral glucose load. Abdominal subcutaneous ATBF was measured using 133Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. Conclusion: After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight‐matched healthy subjects.
Land grabbing or economic development? A modernisation debate enacted on Bugala Island, Uganda

ABSTRACT Globally, the phenomenon of large-scale land leasing, or ‘land grabbing’, is the subject of increasing concern. At the heart of the criticism of this phenomenon is the debate over the most appropriate methods of achieving economic development within the context of a rapidly globalising world. This paper analyzes the process and outcomes of establishing an oil palm plantation on Bugala Island, Uganda. The author asserts that tensions over land use within Uganda reflect incompatible understandings of the relations between land and society and distrust amongst stakeholders. In this case, in spite of these incompatibilities and distrust, the plantation has resulted in positive results for both local land users and the national economy. Yet at the same time, it demonstrates a traditional approach to land use that ignores past injustice and does not recognise power differentials.
Is Exposure to Tobacco Advertising, Promotion and Sponsorship Associated with Initiation of Tobacco Use among Current Tobacco Users in Youth in India?

BACKGROUND The rise in consumption of tobacco products among youth is a public health concern in India. Several studies have shown that advertisements promoting tobacco products influence decisions and behaviour of youth towards smoking. OBJECTIVE To ascertain which method of Tobacco Advertising, Promotion and Sponsorship (TAPS) was more influential for initiating tobacco use in youth in India. MATERIALS AND METHODS The secondary data of youth (15-24 years) from nationally representative Global Adult Tobacco Survey (GATS) conducted in 2009-2010 was analyzed. Odds ratio and p-value were used to know the association between TAPS and initiation of use of tobacco products among youth. Logistic regression was used to determine the most significant means of TAPS altering the youth's behaviour towards tobacco products. RESULTS Out of 13,383 youths, 1,982 (14.7%) used smokeless forms of tobacco and 860 (6.38%) used smoke forms. Logistic regression reveals that promotional activities mainly through cinemas (p<0.05) and providing free samples of tobacco products (p<=.001) were most influential means of initiating consumption of tobacco products among youth. CONCLUSIONS The smoking in youth is associated with watching advertisements particularly in cinema and promotional activities like distribution of free samples, coupons and sales on the price of tobacco products. Stronger legislative measures should be enforced to curb promotional advertisements in cinemas and distribution of free samples.
Autoimmune bullous disorders

Abstract Bullous skin diseases represent a group of organ-specific autoimmune disorders characterised by binding of circulating autoantibodies to adhesion molecules of the epidermis and the dermo-epidermal basement membrane zone. Binding of these autoantibodies to their antigenic targets results in loss of adhesion between epidermal keratinocytes and at the level of the basement membrane zone. Chronic blisters and secondary painful erosions are the clinical hallmark of autoimmune bullous disorders. Histopathology reveals the location of blister formation and helps to classify the subtype of the bullous skin disorder. Immunofluorescence is crucial for diagnosing autoimmune bullous skin disorders. Tissue-bound autoantibodies are detected by direct immunofluorescence of perilesional skin. Circulating autoantibodies can be visualised by indirect immunofluorescence using tissue substrates such as monkey oesophagus and sodium chloride-split human skin. Most of the autoantigens are available as recombinant proteins, which allows for autoantibody screening by ELISA or immunoblot analysis to confirm the primary diagnosis and, importantly, for immunoserological follow-up of patients.
Clinical importance of increased sensitivity of BacT/Alert FAN aerobic and anaerobic blood culture bottles

Two recent multicenter blood culture studies found that BacT/Alert FAN (FAN) bottles (Organon Teknika, Durham, N.C.) had increased yields in detecting bacteremia and fungemia compared with standard BacT/Alert (STD) bottles. Because the clinical importance of this increase in microbial recovery is unknown, we performed a retrospective analysis to determine the frequency with which FAN bottles were the sole means of detecting an episode of bacteremia. There were 1,047 positive blood cultures in which both study bottles were adequately filled and the organism isolated was judged to be the cause of sepsis: 240 (23%) were positive only in FAN bottles and 73 (7%) were positive only in STD bottles. Of a total of 664 episodes of bacteremia, 126 (19%) were identified only by FAN bottles and 43 (7%) were identified only by STD bottles (P < 0.0001). Episodes detected only by FAN bottles more often were recurrent events (23 of 126, or 18%) than episodes detected only by STD bottles (2 of 43, or 5%) (P < 0.05) and more commonly occurred in patients receiving theoretically effective antibiotic therapy (33 of 126 [26%] versus 4 of 43 [9%]) (P < 0.05). The medical records for patients with 127 of these episodes (92 FAN bottles only; 35 STD bottles only) were available for review. More than half of both FAN bottle-only (60 of 92, or 65%) and STD bottle-only (20 of 35, or 57%) episodes were judged to be clinically important. We conclude that FAN bottles improve the detection of bacteremia and that the majority of the additional episodes detected are clinically important. The benefits of the greater yield in specific patient populations must be balanced against the higher costs of FAN bottles.
Control of Cajal body number is mediated by the coilin C-terminus

Cajal bodies (CBs) are nuclear suborganelles implicated in the post-transcriptional maturation of small nuclear and small nucleolar RNAs. The number of CBs displayed by various cell lines and tissues varies, and factors that control CB numbers within a given cell have yet to be described. In this report, we show that specific regions within the C-terminus of coilin, the CB marker protein, are responsible for regulating the number of nuclear foci. Despite the fact that the coilin N-terminal domain is responsible for its self-oligomerization activity, truncation or mutation of predicted sites of phosphorylation in the conserved C-terminal region leads to a striking alteration in the number of nuclear bodies. Similarly, coilin constructs from various species display differential propensities to form nuclear foci when expressed in heterologous backgrounds. We mapped the domain responsible for this variability to the coilin C-terminus utilizing chimeric proteins. Furthermore, the activities responsible for regulating coilin self-association must reside in the nucleus, as constructs lacking critical nuclear localization sequences fail to form foci in the cytoplasm. Factors controlling the putative signal transduction cascade that phosphorylates coilin are also discussed. The results point to a model whereby phosphorylation of the coilin C-terminus regulates the availability of the N-terminal self-interaction domain.
Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis.
A Longitudinal Study of Aboriginal Images in Annual Reports: Evidence from an Arts Council

This paper provides a longitudinal analysis of Aboriginal and Torres Strait Islander imagery use in the annual reports (ARs) of the Australia Council for the Arts (ACA). Content analysis based on imagery, textual narrative and para-text analyses of ARs over 43 years (1973-2015) reveals that the nature and extent of Aboriginal images in ACA's ARs systematically varies with the broader contemporary socio-political and economic developments. Our findings provide insights on an institutional response to the portrayal and shaping of the identity of a key stakeholder group, i.e. Aboriginal artists, which are associated with gaining and maintaining organisational legitimacy.
TSPY and Male Fertility

Spermatogenesis requires the concerted action of thousands of genes, all contributing to its efficiency to a different extent. The Y chromosome contains several testis-specific genes and among them the AZF region genes on the Yq and the TSPY1 array on the Yp are the most relevant candidates for spermatogenic function. TSPY1 was originally described as the putative gene for the gonadoblastoma locus on the Y (GBY) chromosome. Besides its oncogenic properties, expression analyses in the testis and in vitro and in vivo studies all converge on a physiological involvement of the TSPY1 protein in spermatogenesis as a pro-proliferative factor. The majority of TSPY1 copies are arranged in 20.4 kb of tandemly repeated units, with different copy numbers among individuals. Our recent study addressing the role of TSPY1 copy number variation in spermatogenesis reported that TSPY1 copy number influences spermatogenic efficiency and is positively correlated with sperm count. This finding provides further evidence for a role of TSPY1 in testicular germ cell proliferation and stimulates future research aimed at evaluating the relationship between the copy number and the protein expression level of the TSPY1 gene.
The motives of China’s foreign aid

This chapter discusses the political, economic, and humanitarian motives driving Chinese aid. Concerning the political drivers, the Chinese government uses aid as a foreign policy tool, which should help the country to create a favorable international environment for China’s development, support the country’s rise to global power status, influence global governance, and reward countries that abide by the One-China Policy. Moreover, aid has increasingly been used to promote trade with developing countries and loans are extended in exchange for natural resources. Finally, China emphasizes that it gives aid in order to help other developing countries to reduce poverty and improve people’s livelihoods, a claim supported by the data as poorer countries receive more support. While the mixture of political, economic and humanitarian goals does not set China apart from the so-called “traditional” Western donors, China differs in the detailed content of its interests and the explicit emphasis on “mutual benefit” in the pursuance of its goals. Acknowledgements: Excellent research assistance was provided by Samuel Siewers and Felix Turbanisch. We further thank Jamie Parsons for proof-reading of an earlier version of this chapter. This is a draft chapter. The final version will be available in the Handbook of the International Political Economy of China edited by Ka Zeng, forthcoming, Edward Elgar Publishing Ltd The material cannot be used for any other purpose without further permission of the publisher, and is for private use only.
An Allometric Model of Remifentanil Pharmacokinetics and Pharmacodynamics

Background: Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide range of age and weight. Methods: Remifentanil pharmacokinetic data were obtained from three previously published studies of adults and children, one of which also contained pharmacodynamic data from adults. NONMEM was used to estimate allometrically scaled compartmental pharmacokinetic and pharmacodynamic models. Weight, age, height, sex, and body mass index were explored as covariates. Predictive performance was measured across young children, children, young adults, middle-aged, and elderly. Results: Overall, 2,634 remifentanil arterial concentration and 3,989 spectral-edge frequency observations from 131 individuals (55 male, 76 female) were analyzed. Age range was 5 days to 85 yr, weight range was 2.5 to 106 kg, and height range was 49 to 193 cm. The final pharmacokinetic model uses age, weight, and sex as covariates. Parameter estimates for a 35-yr-old, 70-kg male (reference individual) are: V1, 5.81 l; V2, 8.82 l; V3, 5.03 l; CL, 2.58 l/min; Q2, 1.72 l/min; and Q3, 0.124 l/min. Parameters mostly increased with fat-free mass and decreased with age. The pharmacodynamic model effect compartment rate constant (ke0) was 1.09 per minute (reference individual), which decreased with age. Conclusions: We developed a pharmacokinetic-pharmacodynamic model to predict remifentanil concentration and effect for a wide range of patient ages and weights. Performance exceeded the Minto model over a wide age and weight range.
Money, Asset Markets and Efficiency of Capital Formation

Holdings of money and illiquid assets are likely to be determined jointly. Therefore, frictions that give rise to a need for money may affect capital formation, resulting in either too much or too little investment. Existing models of money and capital however tend to overlook that both types of investment inefficiencies can be equilibrium outcomes. Building upon insights from the New-Monetarist literature, we construct a model in which preference heterogeneity between agents implies that both over- and under-investment can arise. We use our framework to study whether monetary policy can effectively resolve both types of investment inefficiencies, and find that increasing inflation could resolve under-investment inefficiencies while reducing inflation could curb over-investment inefficiencies.