Miracle-dz/UniFAR-FTUs huggingface dataset:
Current concepts of IgE regulation and impact of genetic determinants

Immunoglobulin E (IgE) mediated immune responses seem to be directed against parasites and neoplasms, but are best known for their involvement in allergies. The IgE network is tightly controlled at different levels as outlined in this review. Genetic determinants were suspected to influence IgE regulation and IgE levels considerably for many years. Linkage and candidate gene studies suggested a number of loci and genes to correlate with total serum IgE levels, and recently genome‐wide association studies (GWAS) provided the power to identify genetic determinants for total serum IgE levels: 1q23 (FCER1A), 5q31 (RAD50, IL13, IL4), 12q13 (STAT6), 6p21.3 (HLA‐DRB1) and 16p12 (IL4R, IL21R). In this review, we analyse the potential role of these GWAS hits in the IgE network and suggest mechanisms of how genes and genetic variants in these loci may influence IgE regulation.
Trade‐off between steady and unsteady swimming underlies predator‐driven divergence in Gambusia affinis

Differences in predation intensity experienced by organisms can lead to divergent natural selection, driving evolutionary change. Western mosquitofish (Gambusia affinis) exhibit larger caudal regions and higher burst‐swimming capabilities when coexisting with higher densities of predatory fish. It is hypothesized that a trade‐off between steady (constant‐speed cruising; important for acquiring resources) and unsteady (rapid bursts and turns; important for escaping predators) locomotion, combined with divergent selection on locomotor performance (favouring steady swimming in high‐competition scenarios of low‐predation environments, but unsteady swimming in high‐predation localities) has caused such phenotypic divergence. Here, I found that morphological differences had a strong genetic basis, and low‐predation fish required less hydromechanical power during steady swimming, leading to increased endurance. I further found individual‐level support for cause‐and‐effect relationships between morphology, swimming kinematics and endurance. Results indicate that mosquitofish populations inhabiting low‐predation environments have evolved increased steady‐swimming abilities via stiffer bodies, larger anterior body/head regions, smaller caudal regions and greater three‐dimensional streamlining.
Low-tar cigarettes: bane or benefit.

Modern cigarettes are generally low in tar (which includes many toxic products) and nicotine although not always in carbon monoxide delivery. The natural experiments available to epidemiologists, however, have not shown a very positive reduction in mortality that can be attributed to the lowering of tar. Campaigns by public health bodies have sometimes appeared to be effective in persuading the tobacco industry to lower tar generally (for example, Australia), but such low tar campaigns have been used by the tobacco industry to promote smoking itself and to sell the view that the habit is not as dangerous as it was (for example, U.K.). Outside the U.S., there has been very little advertising that features tar content. Comparisons made in sophisticated countries may not be relevant to developing countries. The matter of tar delivery by Third World smoking products needs attention. There is little argument that cigarettes should be lower in tar. There is, however, argument as to whether an optimal dose of nicotine reward is needed in order to prevent the development of compensatory smoking habits. There is also argument as to how the levels of tar and other toxic constituents in cigarettes should be lowered. Legislation and taxation are probably better weapons than public health advertising campaigns.
Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics

The synergy between Mycobacterium tuberculosis (Mtb) and HIV-1 interferes with therapy and facilitates pathogenesis of both human pathogens. Fundamental mechanisms by which Mtb exacerbates HIV-1 are not clear. Here, we show that exosomes secreted by macrophages infected with Mtb, including drug-resistant clinical strains, reactivate HIV-1 by inducing oxidative stress. Mechanistically, Mtb-specific exosomes realign mitochondrial and non-mitochondrial oxygen consumption rate (OCR) and modulates the expression of genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics revealed the enrichment of several host factors (e.g., HIF-1α, galectins, Hsp90) known to promote HIV-1 reactivation in the Mtb-specific exosomes. Treatment with a known antioxidant, N-acetyl cysteine, or with the inhibitors of host factors galectins and Hsp90 attenuated HIV-1 reactivation by Mtb-specific exosomes. Our findings uncovered new paradigms for understanding the redox and bioenergetics basis of HIV-TB co-infection, which will enable the design of effective therapeutic strategies.
THE REDUCTION OF HYPERCALCEMIA IN CASES OF POLYCYTHEMIA VERA BY PHENYLHYDRAZINE.

The range of variation in serum calcium is relatively narrow in health and in most diseases. The accepted normal level is from 9 to 11 mgm. for each 100 cc. of serum or plasma. Lowered values for serum calcium have been found in tetany (parathyroid), rickets, nephritis, osteomalacia and sprue; elevated values are rare. High values have been found by Wells in terminal acidosis and by Coates and Raiment in gout, averaging 19 mgm. for each 100 cc. of serum; these data, however, have been questioned by Cameron. Horowitz has reported values as high as 16.8 mgm. for each 100 cc. of serum in cases of acute gout, and values as high as 16.2 mgm. in five of fourteen cases of arthritis deformans. Hench found that the serum calcium was normal in four cases of gout and in twenty-five cases of infectious arthritis. The calcium content of the whole blood in healthy subjects has been found by Kramer and Tisdall (16) to vary from 5.3 to 6.8 mgm. for each 100 cc. of blood. Calcium is absent, or present in small amounts, in the corpuscles of the blood. The calcium content of the whole blood and of the serum in cases of polycythemia vera has not been carefully studied, probably because of the relative rarity of the disease. Rabinowitch (18), employing McCallum's gravimetric method (quantitative determination of calcium as calcium oxide) found lowered serum calcium in two cases of polycythemia vera.
Functionally Different Agonists Induce Distinct Conformations in the G Protein Coupling Domain of the β2Adrenergic Receptor*

G protein-coupled receptors represent the largest class of drug discovery targets. Drugs that activate G protein-coupled receptors are classified as either agonists or partial agonists. To study the mechanism whereby these different classes of activating ligands modulate receptor function, we directly monitored ligand-induced conformational changes in the G protein-coupling domain of the β2 adrenergic receptor. Fluorescence lifetime analysis of a reporter fluorophore covalently attached to this domain revealed that, in the absence of ligands, this domain oscillates around a single detectable conformation. Binding to an antagonist does not change this conformation but does reduce the flexibility of the domain. However, when the β2 adrenergic receptor is bound to a full agonist, the G protein coupling domain exists in two distinct conformations. Moreover, the conformations induced by a full agonist can be distinguished from those induced by partial agonists. These results provide new insight into the structural consequence of antagonist binding and the basis of agonism and partial agonism.
Can we rely on lymphovascular invasion for determining the need for adjuvant chemotherapy in organ‐confined bladder cancer?

1 Palou J, Hern andez C, Solsona E et al. Effectiveness of hexaminolevulinate fluorescence cystoscopy for the diagnosis of non-muscle-invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study. BJU Int 2015; 116: 37–43 2 Burger M, Grossman HB, Droller M et al. Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol 2013; 64: 846–54 3 Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Palou J, Algaba F, Vicente-Rodriguez J. Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 2000; 164: 680–4 4 van der Meijden A, Oosterlinck W, Brausi M, Kurth KH, Sylvester R, de Balincourt C. Significance of bladder biopsies in Ta,T1 bladder tumors: a report from the EORTC Genito-Urinary Tract Cancer Cooperative Group. EORTC-GU Group Superficial Bladder Committee. Eur Urol 1999; 35: 267–71 5 Kiemeney LA, Witjes JA, Heijbroek RP, Koper NP, Verbeek AL, Debruyne FM. Should random urothelial biopsies be taken from patients with primary superficial bladder cancer? A decision analysis Br J Urol 1994; 73: 164–71 6 Gravas S, Efstathiou K, Zachos I, Melekos MD, Tzortzis V. Is there a learning curve for photodynamic diagnosis of bladder cancer with hexaminolevulinate hydrochloride? Can J Urol 2012; 19: 6269–73
Covariant path integral for chiral p-forms.

The covariant path integral for chiral bosons obtained by McClain, Wu, and Yu is generalized to chiral {ital p}-forms. In order to handle the reducibility of the gauge transformations associated with the chiral {ital p}-forms and with the new variables (in infinite number) that must be added to eliminate the second class constraints, the field-antifield formalism is used. {copyright} {ital 1996 The American Physical Society. }
Prion Protein Glycosylation Is Sensitive to Redox Change*

The conversion of soluble prion protein into an insoluble, pathogenic, protease-resistant isoform is a key event in the development of prion diseases. Although the mechanism by which the conversion engenders a pathogenic event is unclear, there is increasing evidence to suggest that this may depend on the function of the prion protein in preventing oxidative damage. Therefore, in this study, we assessed the interrelationship between redox-sensitive cysteine, glycosylation, and prion metabolism. Cells were treated with a thioreductant, dithiothreitol, to assess the effect of the cellular oxidation state on the synthesis of the prion protein. This change in redox balance affected the glycosylation of the prion protein, resulting in the sole production of glycosylated forms. The role of the single disulfide bridge in mediating this effect within the prion protein was confirmed by mutating the cysteine residues involved in its formation. These data suggest that conditions that increase the rate of formation of the disulfide bridge favor formation of the unglycosylated prion protein. Thus, since the presence of glycans on the prion protein is protective against its pathogenic conversion, a change in the redox status of the cell would increase the risk of developing a prion disease by favoring the production of the unglycosylated form.
Three Channel-Spacing Switchable Multiwavelength Fiber Laser With Two Segments of Polarization-Maintaining Fiber

A three channel-spacing tunable multiwavelength fiber ring laser by using two segments of polarization-maintaining fiber (PMF) is experimentally demonstrated. By adjusting the polarization controllers, the wavelength spacing could be efficiently switched among 0.48, 0.73, and 1.45 nm. Moreover, we also analyzed theoretically the equivalent Lyot birefringence fiber filter with two segments of PMF. Theoretical prediction was verified by experimentally obtained multiwavelength outputs.
A Fuel Cell Power Conditioning System With Low-Frequency Ripple-Free Input Current Using a Control-Oriented Power Pulsation Decoupling Strategy

This paper proposes a fuel cell power conditioning system based on the current-fed dual-half-bridge (CF-DHB) dc-dc converter that can achieve low-frequency ripple-free input current using a control-oriented power pulsation decoupling strategy when an inverter load is connected to the fuel cell system. Without adding any extra circuit components, the proposed power pulsation decoupling strategy can realize a smaller dc bus capacitor; a film capacitor, therefore, can be applied in this fuel cell power conditioning system to replace the bulky electrolytic capacitor. In order to eliminate the double-frequency ripple current disturbance introduced by the inverter load to the fuel cell stack, a proportional-resonant controller is developed to achieve an extra high control gain at a designed resonant frequency. The operation principles of the CF-DHB converter with a proposed power pulsation decoupling strategy are analyzed. In addition, the controller design guidelines are derived based on the system small-signal model. The experimental results of a 1-kW fuel cell power conditioning system are presented to validate the proposed technology.
Transitions in coral reef accretion rates linked to intrinsic ecological shifts on turbid-zone nearshore reefs

Nearshore coral communities within turbid settings are typically perceived to have limited reef-building capacity. However, several recent studies have reported reef growth over millennial time scales within such environments and have hypothesized that depth-variable community assemblages may act as equally important controls on reef growth as they do in clear-water settings. Here, we explicitly test this idea using a newly compiled chronostratigraphic record (31 cores, 142 radiometric dates) from seven proximal (but discrete) nearshore coral reefs located along the central Great Barrier Reef (Australia). Uniquely, these reefs span distinct stages of geomorphological maturity, as reflected in their elevations below sea level. Integrated age-depth and ecological data sets indicate that contemporary coral assemblage shifts, associated with changing light availability and wave exposure as reefs shallowed, coincided with transitions in accretion rates at equivalent core depths. Reef initiation followed a regional ∼1 m drop in sea level (1200–800 calibrated yr B.P.) which would have lowered the photic floor and exposed new substrate for coral recruitment by winnowing away fine seafloor sediments. We propose that a two-way feedback mechanism exists where past growth history influences current reef morphology and ecology, ultimately driving future reef accumulation and morphological change. These findings provide the first empirical evidence that nearshore reef growth trajectories are intrinsically driven by changes in coral community structure as reefs move toward sea level, a finding of direct significance for predicting the impacts of extrinsically driven ecological change (e.g., coral-algal phase shifts) on reef growth potential within the wider coastal zone on the Great Barrier Reef.
Sequential detection in radar with multiple resolution elements

In this paper the techniques of sequential analysis are applied to a multiple-resolution-element search radar for different types of detection. By using sequential methods such a radar shows considerable saving compared to fixed-scan-rate detection radars. Many of the problems occurring in sequential radar detection are examined; the difficulties of obtaining analytical results for multiple-resolution-element sequential radars are discussed. Most of the results of this paper were obtained by simulation. Included are interesting results which suggest that truncation is not necessary for the tests which were considered. Curves are given describing the improvement obtained by sequential detection procedures. The curves are discussed in detail to make this paper useful to those whose primary interest is in the results which are obtained.
Phenotype of two males with abnormal Y chromosomes

Two infertile males with sex chromosomal abnormalities and mosaic karyotype, 45,X/ 46,X,dic(Yq) and 45,X/46,X,ring(Y), had considerably changed physical findings, including tooth sizes and craniofacial dimensions. Spermatogenesis was preserved with abnormal meiotic chromosomal behaviour. Mosaic karyotype and structurally changed Y chromosome in both cases had an influence on physical parameters. Testes were normally developed and spermatogenesis was preserved but depressed in later stages.
The Origin and Mechanism of Circulating DNA

Although it is evident that DNA circulates freely in blood plasma both in disease and in health, the source of this DNA remains enigmatic. It can be presumed that circulating DNA in healthy subjects derives from lymphocytes or other nucleated cells. Yet, it is not known why cancer patients have such large quantities of plasma DNA. There is no doubt that a proportion seems to originate from nucleated blood cells since wild-type DNA has been detected in the plasma of all cancer patients studied as well as in that of healthy controls. However, a substantial proportion of plasma DNA in cancer patients derives from tumor cells. This latter concept is supported by both quantitative and qualitative observations. Plasma DNA levels are not only greater in cancer patients than in normal subjects,1–5 but also correlate inversely with outcome and tend to fall with effective treatment.1,5 In addition, the ability to detect LOH in plasma DNA6–13 suggests that tumor-related DNA is the predominant subtype in at least some cancer patients. What is responsible for the presence of tumor DNA shed in the bloodstream? It could be due to lysis of circulating cancer cells or of micrometastases, to DNA leakage resulting from tumor necrosis or apoptosis, or to a new mechanism of active release.
Heat Shock Proteins and Scavenger Receptors: Role in Adaptive Immune Responses

Tumor-derived heat shock proteins have shown promise as anti-cancer vaccines in clinical trials. Heat shock proteins (HSPs) can generate potent anti-tumor immunity and elicit antigen-specific CD8 + T cell responses in murine studies. Antigen presenting cells (APC), such as macrophages and dendritic cells (DCs), can elicit antigen-specific CD8 + T cell responses mediated by HSPs. CD91 was the first identified endocytic scavenger receptor for HSPs on APC that can facilitate the process of cross-presentation. Other scavenger receptors may also play a similar role in this process. The present review critically evaluates the identified HSP endocytic receptors on APCs that may generate adaptive immune responses. A better understanding of this interaction between HSPs and APCs may further unravel mechanisms of immunoadjuvant function of HSPs.
Molecular Cytogenetics of Brain Tumors

Molecular cytogenetics includes a spectrum of methodologies that use molecular reagents to better define chromosomal alterations in normal and neoplastic cells. Brain tumors are a group of neoplasms for which there is a wealth of cytogenetic and molecular genetic information, and some of the newer techniques have extended the types of samples from which genetic information which can be obtained to biopsies and even paraffin-embedded sections. Fluorescence in situ hybridization on interphase nuclei has been used to confirm gains of chromosome 7, loss of chromosome 10, 9p deletion and gene amplification in malignant gliomas, and to visualize isochromosome 17q in medulloblastomas. Comparative genomic hybridization uses genomic DNA to determine gains and losses of chromosomes and chromosomal regions. This approach is particularly useful for identifying gene amplification. For cases in which chromosomal spreads are obtained, chromosomal painting is helpful in determining the origin of chromosomal segments. Several methods are now available in which each of the 22 autosomes and the sex chromosome can be identified by unique colors, termed Spectral karyotyping and multiplex-FISH. These molecular cytogenetic techniques are important clinical and experimental tools that have provided new insight into the genetic alterations of brain tumors.
How is 68Ga Labeling of Macrocyclic Chelators Influenced by Metal Ion Contaminants in 68Ge/68Ga Generator Eluates?

To assess the influence of Zn2+, Cu2+, Fe3+, Al3+, TiIV, and SnIV on incorporation of 68Ga3+ into pendant‐arm macrocyclic chelators, the 68Ga labeling of 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid (NOTA), 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA), 1,4,7‐triazacyclononane‐1,4,7‐tris[methyl(2‐carboxyethyl)phosphinic acid]) (TRAP), and 1,4,7‐triazacyclononane‐1‐[methyl(2‐carboxyethyl)phosphinic acid]‐4,7‐bis[methyl(2‐hydroxymethyl)phosphinic acid] (NOPO), as well as their peptide conjugates, was investigated in the presence of varying concentrations of these metal ions. The 68Ga labeling yield for carboxylate‐type chelators NOTA and DOTA is decreased at lower metal ion contaminant concentrations compared with phosphinate‐type chelators TRAP and NOPO. The latter are able to rapidly exchange coordinated ZnII with 68Ga3+, as confirmed by mass spectrometry and 31P NMR spectroscopy. 68Ga labeling of ZnII complexes of TRAP and NOPO proceeds as efficient as labeling of neat NOTA; this applies also to the corresponding peptide conjugates of these chelators. This behavior results in substantially improved selectivity for Ga3+ and, therefore, in more robust and reliable 68Ga labeling procedures. In addition, none of the investigated chelators binds 68Ge, rendering post‐labeling purification protocols, for example, solid‐phase extraction, a reliable means of removal of 68Ge contamination from 68Ga radiopharmaceuticals.
Quantity and quality of information, education and communication during antenatal visit at private and public sector hospitals of Bahawalpur, Pakistan.

BACKGROUND Information, education and communication (IEC) by health care provider to pregnant woman during the antenatal visit are very crucial for healthier outcome of pregnancy. This study analysed the quality and quantity of antenatal visit at a private and a public hospital of Bahawalpur, Pakistan. METHODS An exit interview was conducted from 216 pregnant women by using validated, reliable and pre-tested adapted questionnaire. First sample was selected by simple random sampling, for rest of the sample selection systematic random sampling was adapted by selecting every 7th women for interview. Ethical considerations were taken. RESULTS Average communication time among pregnant woman and her healthcare provider was 3 minute in public and 8 minutes in private hospital. IEC mainly focused on diet and nutrition in private (86%) and (53%) public, advice for family planning after delivery was discussed with 13% versus 7% in public and private setting. None of the respondents in both facilities got advice or counselling on breastfeeding and neonatal care. Birth preparedness components were discussed, woman in public and private hospital respectively. In both settings antenatal clients were not received information and education communication according to World Health Organization guidelines. CONCLUSION Quality and quantity of IEC during antenatal care was found very poor in both public and private sector hospitals of urban Pakistan.
The reliability index approach with evolutionary algorithms: application to the RBRDO problem of composite structures

A new methodology to solve the Reliability Index Approach (RIA) minimization problem with high levels of accuracy and still with practical efficiency is presented. This method is based on the exclusive use of genetic algorithms with elitist strategy, to make possible to find the global Most Probable Failure Point, in the uncertainty space. To overcome the computational costs inherent to these class of algorithms, the RIA minimization problem is reformulated and a new heuristic is proposed. The method is then applied to the Reliabilitybased Robust Design Optimization problem of composite structures, where minimum weight and maximum system robustness are objectives and the target reliability index is a constraint.