Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of therapy with soluble tumour necrosis factor receptor fusion protein on pulmonary cytokine expression and lung injury following haemorrhage and resuscitation

Acute lung injury frequently develops following haemorrhage, and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in tumour necrosis factor‐alpha (TNF‐α) mRNA expression among pulmonary cell populations which precede the development of lung injury. In order to examine the role of TNP‐α in producing acute inflammatory lung injury, we treated mice following haemorrhage and resuscitation with a TNF antagonist, composed of soluble dimeric human p80 TNF receptor linked to the Fc region of human IgG1 (sTNFR:Fc). Therapy with sTNFR:Fc prevented the post‐haemorrhage increases in circulating and pulmonary TNF‐α levels normally found following blood loss. Administration of sTNFR:Fc also diminished the increase in IL‐1/β, IL–6, TNF‐α and interferon‐gamma (IFN‐γ) mRNA normally found in the lungs following haemorrhage. However, therapy with sTNFR:Fc was not associated with improvement in the histologic parameters of post‐haemorrhage lung injury, such as neutrophil infiltration and interstitial oedema. In contrast lo the effects of sTNFR:Fc on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, such therapy following haemorrhage was associated with increased amounts of mRNA for TNF‐α among peripheral blood mononuclear cells, as well as increased IFN‐γ titres in serum and bronchoalveolar lavage (BAL) specimens. These results indicate that therapy with sTNFR:Fc in the post‐haemorrhage period, although capable of decreasing proinflammatory cytokine expression in the lungs, does not prevent the development of acute lung injury in this setting.
Neurological complications of organ transplantation

Over the last thirty years, organ transplantation has become a practical treatment option for many otherwise fatal diseases. New immunosuppressive agents, advances in tissue matching, and improvements in surgical technique have increased both the number and type of transplants performed. Kidney, bone marrow, heart, lung, liver, and pancreas transplants are now used regularly in the treatment of end‐stage disease. However, these advances have come at a price. Transplant recipients are subject to numerous complications, many of which involve the nervous system. Depending on the type of organ transplanted, 30 to 60% of transplant recipients experience neurological problems. Most neurological complications, especially those related to immunosuppression, are common to all transplant types; other complications are associated predominantly with specific transplant types. This report reviews the general categories of neurological complications as well as the specific problems associated with each kind of transplant.
Radar-aided optical navigation for long and large-scale flights over unknown and non-flat terrain

For flight automation tolerable to satellite navigation dropouts, this paper presents a simultaneous localization and mapping method based on radar altimeter measurements and monocular camera images. The novelty within mapping is the combination of radar distance and image triangulation. This approach verifies whether the radar measurement fits to a specific horizontal plane in the map, yielding the sub-set of image features that do most probably correspond with the radar measurement. With this map match of the radar altitude, ambiguities in the radar measurement can be resolved. Since unusable radar measurements are suppressed, this method is suitable for positioning in non-flat terrain, e.g. in mountain areas. For matched data, the method estimates a scale correction factor for the image projection rays in order to remove scale ambiguities of the monocular navigation. Together with mapping, vehicle localization is done which is essentially camera resectioning. Localization can be parameterized with the required number of degrees of freedom depending on the availability of additional position sensors. The incremental positioning is tested in kilometer-scale outdoor flights of a 30 kg unmanned airplane as well as in flights with a Cessna 172R equipped with camera and radar sensors. The tests show the benefits of the proposed method in flat and hilly terrain, and demonstrate reduction of accumulation errors down to 2-6% over the distance flown. Some constraints of the method for the altitude range are existent, however it is highlighted that this method will generally work on typical flight profiles.
Immunoblot assay using excreted-secreted antigens of Trypanosoma cruzi in serodiagnosis of congenital, acute, and chronic Chagas' disease

Immunoblotting with trypomastigote excreted-secreted antigens (TESA blot) of Trypanosoma cruzi was evaluated as a method for diagnosis of chronic and acute phases as well as congenital (in newborn children) Chagas' disease. Serum samples from acute-phase and congenital infections were considered to be positive when they reacted with ladder-like bands of 130- to 200-kDa antigens, recognized by immunoglobulin M (IgM) and IgG antibodies, while IgG from chronic-phase sera recognized a broad band antigen of 150 to 160 kDa. Nonchagasic sera were not reactive to these antigens. The study was carried out on 512 patients, 111 of whom were nonchagasic but included cases of leishmaniasis or other pathologies, and 401 chagasic patients. The latter group comprised 361 chronic cases, 36 acute cases, and 4 congenital cases in newborn children. Among the chronic cases, 256 were from areas in which T. cruzi is endemic but which differed widely in the pathogenic expression of T. cruzi infection and in parasitemia levels. These patients at the same time showed a broad range of low, medium, and high reactivity to conventional enzyme-linked immunosorbent assays and indirect immunofluorescence serotests for Chagas' disease. For these reasons they may better represent the universe of chagasic patients than would a sample of highly reactive sera obtained from chagasic patients in a single area endemic for T. cruzi. All acute and congenital cases showed positivity in the IgM and IgG TESA blots, while chronic cases were 100% positive for IgG antibodies. In nonchagasic sera, including 30 cases of visceral and muco-cutaneous leishmaniasis, the specificity index was 1.000, and no cross-reactions were observed. The TESA blot thus seems to be useful as a sensitive and specific diagnostic assay in cases of suspected acute or congenital T. cruzi infection and as a general confirmatory test for conventional Chagas' disease serology.
Harmonic analysis of RC-active phase shift oscillators

This paper describes a significantly improved method for calculating the harmonic distortion content of active-RC phase shift oscillators. The proposed method introduces the truncated harmonic transfer function (THTF) which is related to the two-sinusoidal-input describing function (TSIDF) of non-linear control theory. This allows accurate calculation of the distortion terms in oscillator systems containing higher signal levels and therefore higher levels of nonlinearity than is possible with conventional methods. The method is quite general in its application and this paper considers both cubic and quadratic nonlinearities. The method is demonstrated using examples employing the Wien RC-bandpass oscillator with a quadratic nonlinearity.
Identification of Antigenic Targets for Immunodetection of Balamuthia mandrillaris Infection

ABSTRACT The free-living amoeba Balamuthia mandrillaris causes granulomatous amoebic encephalitis (GAE) in humans. Rapid identification of balamuthiasis is critical for effective therapeutic intervention and case management. In the present study we identified target antigens for the development of a serological assay for B. mandrillaris infection. We demonstrated by silver staining that protein profiles for all eight isolates of B. mandrillaris, independent of human or animal origin or geographic origin, appeared to be similar except for some minor differences, indicating the molecular homogeneity of these strains. The profiles of all isolates, which ranged from 200 to 10 kDa, were similar, with a prominent protein visible around 30 kDa; all appeared considerably different from protein profiles of the control E6 cells and Acanthamoeba castellanii and Naegleria fowleri isolates. Western blot analysis with rabbit hyperimmune serum identified the major immunodominant antigens of 25, 50, 75, and 80 kDa; positive human sera reacted strongly with proteins around 25, 40, 50, and 75 kDa. Proteins around 40 kDa detected by human serum were not recognized by hyperimmune rabbit serum. None of the target proteins were detected by uninfected control sera. Reactivities of five patients' sera with 4 different isolates of B. mandrillaris (2 strains of human and 2 strains of animal origins) revealed that patients' sera reacted slightly differently with different B. mandrillaris isolates, although major proteins of approximately 25, 50, and 75 kDa were present in all extracts.
Ligand-independent Activation of the Androgen Receptor by Interleukin-6 and the Role of Steroid Receptor Coactivator-1 in Prostate Cancer Cells*

The androgen receptor (AR) can be activated in the absence of androgens by interleukin-6 (IL-6) in human prostate cancer cells. The events involved in ligand-independent activation of the AR are unknown, but have been suggested to involve phosphorylation of the AR itself or a receptor-associated protein. Steroid receptor coactivator-1 (SRC-1) has been shown to interact with the human AR and to modulate ligand-dependent AR transactivation and is regulated by phosphorylation by MAPK. To date, no one has examined the role of SRC-1 in ligand-independent activation of the AR by IL-6 or other signaling pathways known to activate the full-length receptor. This study addressed this and has revealed the following. 1) SRC-1 similarly enhanced ligand-independent activation of the AR by IL-6 to the same magnitude as that obtained via ligand-dependent activation. 2) Androgen and IL-6 stimulated the MAPK pathway. 3) MAPK was required for both ligand-dependent and ligand-independent activation of the AR. 4) Phosphorylation of SRC-1 by MAPK was required for optimal ligand-independent activation of the AR by IL-6. 5) Protein-protein interaction between endogenous AR and SRC-1 was dependent upon treatment of LNCaP cells with IL-6 or R1881. 6) Protein-protein interaction between the AR N-terminal domain and SRC-1 was independent of MAPK. 7) Ligand-independent activation of the AR did not occur by a mechanism of overexpression of either solely wild-type SRC-1 or mutant SRC-1 that mimics its phosphorylated form.
Novel aphidicolin‐inducible common fragile site FRA9G maps to 9p22.2, within the C9orf39 gene

Common fragile sites represent a component of normal chromosome structure that form gaps and breaks on metaphase chromosomes after partial inhibition of DNA synthesis. In humans, cytogenetic locations of 89 common fragile sites are listed in the Genome Database; however, the exact number of fragile sites remains unknown. The application of high resolution mapping approaches continues to reveal new common fragile sites in the human genome. Here, we identified a novel aphidicolin‐inducible common fragile site FRA9G, which maps to chromosomal band 9p22.2. We have characterized the structure of the fragile DNA sequence that extends over a genomic region of ∼300 kb within the C9orf39 (chromosome 9 open reading frame 39) gene. Analysis of incidence in healthy individuals showed that FRA9G is commonly expressed in the population. Heterozygous BRCA2 mutation carriers exhibit an almost sevenfold increase of FRA9G expression compared to an unrelated control population group. Identification of a novel aphidicolin‐inducible common fragile site at 9p22 may have implications for understanding the mechanism of genetic instability in tumorigenesis and other genetic disorders. © 2007 Wiley‐Liss, Inc.
Both Cleavage Products of the mCLCA3 Protein Are Secreted Soluble Proteins*

Members of the chloride channels, calcium-activated (CLCA) family of proteins and in particular the murine mCLCA3 (alias gob-5) and its human ortholog hCLCA1 have been identified as clinically relevant molecules in diseases with secretory dysfunctions including asthma and cystic fibrosis. Initial studies have indicated that these proteins evoke a calcium-activated chloride conductance when transfected into human embryonic kidney cells 293 cells. However, it is not yet clear whether the CLCA proteins form chloride channels per se or function as mediators of other, yet unknown chloride channels. Here, we present a systematic biochemical analysis of the posttranslational processing and intracellular trafficking of the mCLCA3 protein. Pulse-chase experiments after metabolic protein labeling of mCLCA3-transfected COS-1 or human embryonic kidney 293 cells revealed cleavage of a primary 110-kDa mCLCA3 translation product in the endoplasmic reticulum into a 75-kDa amino-terminal and a 35-kDa carboxyl-terminal protein that were glycosylated and remained physically associated with each other. Confocal fluorescent analyses identified both cleavage products in vesicles of the secretory pathway. Neither cleavage product was associated with the cell membrane at any time. Instead, both subunits were fully secreted into the extracellular environment as a soluble complex of two glycoproteins. These results suggest that the two mCLCA3 cleavage products cannot form an anion channel on their own but may instead act as extracellular signaling molecules. Furthermore, our results point toward significant structural differences between mCLCA3 and its human ortholog, hCLCA1, which is thought to be a single, non-integral membrane protein.
Sequence-specific Binding Protein of Single-stranded and Unimolecular Quadruplex Telomeric DNA from Rat Hepatocytes*

A rat liver nuclear protein, unimolecular quadruplex telomere-binding protein 25, (uqTBP25) is described that binds tightly and specifically single-stranded and unimolecular tetraplex forms of the vertebrate telomeric DNA sequence 5′-d(TTAGGG) n -3′. A near homogeneous uqTBP25 was purified by ammonium sulfate precipitation, chromatographic separation from other DNA binding proteins, and three steps of column chromatography. SDS-polyacrylamide gel electrophoresis and Superdex© 200 gel filtration disclosed for uqTBP25 subunit and nativeM r values of 25.4 ± 0.5 and 25.0 kDa, respectively. Sequences of uqTBP25 tryptic peptides were closely homologous, but not identical, to heterogeneous nuclear ribonucleoprotein A1, heterogeneous nuclear ribonucleoprotein A2/B1, and single-stranded DNA-binding proteins UP1 and HDP-1. Complexes of uqTBP25 with single-stranded or unimolecular quadruplex 5′-d(TTAGGG)4-3′, respectively, had dissociation constants,K d , of 2.2 or 13.4 nm. Relative to d(TTAGGG)4, complexes with 5′-r(UUAGGG)4-3′, blunt-ended duplex telomeric DNA, or quadruplex telomeric DNA had >10 to >250-fold higher K d values. Single base alterations within the d(TTAGGG) repeat increased theK d of complexes with uqTBP25 by 9–215-fold. Association with uqTBP25 protected d(TTAGGG)4 against nuclease digestion, suggesting a potential role for the protein in telomeric DNA transactions.
Interaction Effects of Neighborhood Disadvantage and Individual Social Support on Frequency of Alcohol Use in Youth Living with HIV

Youth living with HIV (YLH) experience multiple disease-related stresses along with the same structural and developmental challenges faced by their uninfected peers; alcohol use among YLH represents a risk behavior by virtue of potential effects on youth health and increased likelihood of engaging in unprotected sex while drinking alcohol. Research aimed at better understanding the interplay of individual- and neighborhood-level influences on alcohol use for YLH is needed to inform interventions. This study examined whether socioeconomic disadvantage (SED) and social support influence, independently and through interaction, alcohol use in YLH. Data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) consisted of YLH across 538 neighborhoods in the United States who acquired HIV behaviorally. Neighborhood-specific data were compiled from the 2010 U.S. Census Bureau and matched with individual-level data from the ATN (N = 1,357) to examine effects that contribute to variation in frequency of alcohol use. Other drug use, being male, being non-Black, and older age were associated with greater alcohol use. Higher social support was negatively associated with alcohol use frequency. A cross-level interaction indicated that the association found between decreasing social support and increasing alcohol use frequency was weakened in areas with lower SED. Implications are discussed.
A Multitasking Electrical Impedance Tomography System Using Titanium Alloy Electrode

This paper presents a multitasking electrical impedance tomography (EIT) system designed to improve the flexibility and durability of an existing EIT system. The ability of the present EIT system to detect, locate, and reshape objects was evaluated by four different experiments. The results of the study show that the system can detect and locate an object with a diameter as small as 1.5 mm in a testing tank with a diameter of 134 mm. Moreover, the results demonstrate the ability of the current system to reconstruct an image of several dielectric object shapes. Based on the results of the experiments, the programmable EIT system can adapt the EIT system for different applications without the need to implement a new EIT system, which may help to save time and cost. The setup for all the experiments consisted of a testing tank with an attached 16-electrode array made of titanium alloy grade 2. The titanium alloy electrode was used to enhance EIT system's durability and lifespan.
The influences of place of birth and socioeconomic factors on attempted suicide in a defined population of 4.5 million people.

BACKGROUND Our knowledge of the influence of place of birth and socioeconomic status on attempted suicide in a defined national population is limited. METHODS The study population at baseline in 1993 included approximately 4.5 million Swedish persons aged 25 to 64 years, of whom 570 000 had been born abroad. Each individual was tracked until attempted suicide, remigration, death, or the end of the study on December 31, 1998. The Cox regression was used in the analysis. RESULTS Labor migrants from Finland and other OECD (Organisation for Economic Cooperation and Development) countries and refugees from Poland and Iran had higher hazard ratios of attempted suicide than Swedish-born control subjects. Women born in Latin America, Asia, and Eastern Europe had significantly higher hazard ratios of attempted suicide than Swedish-born women. In contrast, men born in southern Europe and Asia had significantly lower hazard ratios of attempted suicide. The hazard ratios of attempted suicide among women from Iran, Asia, southern Europe, Latin America, and eastern Europe considerably exceeded those of men from the same country of origin. When socioeconomic status was included in the final model, the hazard ratios remained high for women, while the risk of attempted suicide among men declined sharply with increased income. CONCLUSIONS Place of birth, socioeconomic status, and sex are associated with attempted suicide. Socioeconomic status explains only part of the association between place of birth and attempted suicide.
Crack-Cocaine Use Accelerates HIV Disease Progression in a Cohort of HIV-Positive Drug Users

Background:HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. Methods:A prospective, 30-month, longitudinal study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4+ cell count, and viral load were performed every 6 months. Results:Crack-cocaine users were 2.14 times [95% confidence interval (CI): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to ≤200 cells/mL, independent of antiretroviral use. Viral load over 30 months was significantly higher in crack users (β = 0.315, P = 0.037) independent of highly active antiretroviral therapy (HAART) over time. The only multidrug combination that significantly increased the risk of disease progression was crack cocaine with marijuana (hazard ratio = 2.42; 95% CI: 1.042 to 5.617, P = 0.04). Of those on HAART, a significantly lower proportion of crack-cocaine users versus nonusers had controlled viral load (P < 0.001), suggesting lower medication adherence, whereas crack-cocaine users not on HAART showed a greater risk for HIV disease progression than nonusers (hazard ratio = 3.946; 95% CI: 1.049 to 14.85, P = 0.042). Conclusions:Crack-cocaine use facilitates HIV disease progression by reducing adherence in those on HAART and by accelerating disease progression independently of HAART.
Monoclonal antibodies to Escherichia coli heat-labile enterotoxins: neutralising activity and differentiation of human and porcine LTs and cholera toxin.

Forty-four monoclonal antibodies (MAbs) prepared against heat-labile enterotoxins (LTs) from human (LTh) or porcine (LTp) E. coli isolates were characterised, especially with regard to their reactivity with epitopes shared with the heterologous LT and/or cholera toxin (CT), and their toxin neutralising activity. Of 24 MAbs against LTh (all directed against the B subunit portion) 12 cross-reacted with LTp and CT, 4 with LTp but not CT, and 1 with CT but not LTp; 7 MAbs reacted with LTh epitope(s) not shared by either LTp or CT. Among 20 MAbs against LTp (9 directed against the B subunits and 11 against the A subunit) 2 cross-reacted with LTh as well as CT, 13 with LTh but not CT, and 5 MAbs were specific for LTp. Irrespective of whether the anti-LT MAbs were directed against shared or unshared epitopes, or against the A or B subunits, they neutralised their homologous toxin in direct proportion to their toxin-binding titre. The results show how minute differences in enterotoxin primary structures e.g., the LTh and LTp B chains differ in only 4 of 103 amino acid residues, are associated with antigenic epitopes against which toxin-differentiating MAbs with neutralising activity can be produced. Such MAbs are promising tools for species-specific diagnostic detection of enterotoxins in clinical specimens.
Iatrogenic Creutzfeldt–Jakob disease at the millennium

Article abstract The causes and geographic distribution of 267 cases of iatrogenic Creutzfeldt–Jakob disease (CJD) are here updated at the millennium. Small numbers of still-occurring cases result from disease onsets after longer and longer incubation periods following infection by cadaveric human growth hormone or dura mater grafts manufactured and distributed before the mid-1980s. The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4% in different countries, and acquisition from dura mater varies between 0.02 and 0.05% in Japan (where most cases occurred). Incubation periods can extend up to 30 years, and cerebellar onsets predominate in both hormone and graft recipients (in whom the site of graft placement had no effect on the clinical presentation). Homozygosity at codon 129 of the PRNP gene is over-represented in both forms of disease; it has no effect on the incubation period of graft recipients, but may promote shorter incubation periods in hormone cases. Knowledge about potential high-risk sources of contamination gained during the last quarter century, and the implementation of methods to circumvent them, should minimize the potential for iatrogenic contributions to the current spectrum of CJD.