Miracle-dz/UniFAR-FTUs huggingface dataset:
MyD88 Signaling Contributes to Early Pulmonary Responses to Aspergillus fumigatus

ABSTRACT Toll-like receptors and the β-glucan receptor, dectin-1, mediate macrophage inflammatory responses to Aspergillus fumigatus through MyD88-dependent and -independent signaling mechanisms; however, pulmonary inflammatory responses in MyD88-deficient mice challenged with A. fumigatus are poorly defined. The role of MyD88 signaling in early pulmonary inflammation and fungal clearance was evaluated in C57BL/6J wild-type (WT) and MyD88-deficient (MyD88−/−) mice. Early (<48 h) after infection, MyD88−/− mice had higher fungal burdens than those of WT mice, although fungal burdens rapidly declined (>72 h) in both. MyD88−/− mice had less consolidated inflammation, with fewer NK cells, in lung tissue early (24 h) after infection than did WT mice. At the latter time point, MyD88−/− mouse lungs were characterized by a large amount of necrotic cellular debris and fibrin, while WT lungs had organized inflammation. Although there were equivalent numbers of macrophages in WT and MyD88−/− mouse lung tissues, MyD88−/− cells demonstrated delayed uptake of green fluorescent protein-expressing A. fumigatus (GFP-Af293); histologically, MyD88−/− mouse lungs had more hyphal invasion of terminal airways and vessels, the appearance of bronchiolar epithelial cell necrosis, and necrotizing vasculitis. MyD88−/− lung homogenates contained comparatively decreased amounts of interleukin-1β (IL-1β), IL-6, KC, and gamma interferon and paradoxically increased amounts of tumor necrosis factor alpha and macrophage inflammatory protein 1α. These data indicate that the MyD88-dependent pathway mediates acute pulmonary fungal clearance, inflammation, and tissue injury very early after infection. Resolution of abnormalities within a 3-day window demonstrates the importance of redundant signaling pathways in mediating pulmonary inflammatory responses to fungi.
Co‐existence of P2Y‐ and PPADS‐insensitive P2U‐purinoceptors in endothelial cells from adrenal medulla

1 We have studied the effects of purinoceptor stimulation on Ca2+ signals in bovine adrenomedullary endothelial cells. [Ca2+]i was determined with the fluorescent probe fura‐2 both in population samples and in single, isolated, endothelial cells in primary culture and after subculturing. 2 In endothelial cells, maintained in culture for more than one passage, several purinoceptor agonists elicited clear [Ca2+]i transient peaks that remained in the absence of extracellular Ca2+. Adenosine 5′‐triphosphate (ATP) and uridine 5′‐triphosphate (UTP) were equipotently active, with EC50 values of 8.5 ± 0.9 μm and 6.9 ± 1.5 μm, respectively, whereas 2‐methylthioadenosine 5′‐triphosphate (2MeSATP), adenosine 5′‐(α, β‐methylene)triphosphate (α, β‐MeATP) and adenosine(5′)tetraphospho(5′)adenosine (AP4A) were basically inactive. Adenosine 5′‐O‐(2‐thiodiphosphate) (ADPβS) was a weak agonist. The apparent potency order was UTP = ATP > ADPβS > > 2MeSATP > α, β‐MeATP. 3 Cross‐desensitization experiments revealed that UTP or ATP, added sequentially at concentrations of maximal effect, could completely abolish the [Ca2+]i response to the second agonist. ADPβS exerted only a partial desensitization of the response to maximal ATP, in accordance with its lower potency in raising [Ca2+]i. 4 The effect on [Ca2+]i of 100 μm ATP in subcultured cells was reduced by only 25% with 100 μm suramin pretreatment and was negligibly affected by exposure to 10 μm pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS). The concentration‐effect curve for ATP was not significantly affected by PPADS, but was displaced to the right by a factor of 6.5 by 100 μm suramin. 5 In primary cultures, clear [Ca2+]i responses were elicited by 2MeSATP. Suramin totally and selectively blocked 2MeSATP responses, whereas UTP‐evoked [Ca2+]i transients were mainly unaffected by suramin or PPADS. Over 80% of cells tested showed responses to both 2MeSATP and UTP. The [Ca2+]i response to UTP was not desensitized in the presence of 2MeSATP. 6 ATP and UTP stimulated the release of preloaded [3H]‐arachidonic acid ([3H]‐AA), both in the presence and in the absence of extracellular Ca2+, by approximately 135% with respect to basal levels. Suramin and PPADS enhanced, rather than inhibited, the [3H]‐AA releasing effect of ATP by 2.5 times. Suramin also potentiated the effect of the calcium ionophore A23187. 7 These results indicate that endothelial cells from adrenomedullary capillaries co‐express both P2Y‐and P2U‐purinoceptors. P2Y‐purinoceptors are lost in culture with the first passage of the cells. The P2U‐purinoceptor subtype present in these cells is insensitive to PPADS and thus similar to that found in aortic endothelial cells.
αB‐crystallin as a marker of lymph node involvement in breast carcinoma

It was found previously that αB‐crystallin, a small heat‐shock protein, was overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The objective of the current study was to determine whether the expression of αB‐crystallin in primary breast carcinomas was associated with lymph node metastasis and survival.
Fluorescent-Antibody Approach to Study of Rhizobia in Soil

Application of fluorescent-antibody (FA) techniques to the study of rhizobia as free-living soil bacteria was explored. Antiserum to a particular strain of Rhizobium japonicum proved specific in both agglutination and FA tests. Within the R. japonicum group, 2 of 12 strains were stained by the conjugate and these fluoresced brightly; all others were entirely negative. FA tests were negative for 7 strains of R. meliloti, 9 strains of R. leguminosarum, 9 strains of R. trifolii, 6 strains of R. phaseoli, and 65 unidentified bacteria isolated from 12 soils. R. japonicum grew in autoclaved soil and was readily detectable by FA examination of contact slides. The FA technique also detected antibody-reacting bacteria in a field soil whose rhizobial content was unknown. Fluorescent cells were probably R. japonicum, since nodules developed on soybean plants grown in the same soil sample and FA preparations of the crushed nodules proved positive. Autofluorescence was not a problem, but nonspecific adsorption of conjugate restricted observations to microscopic fields free from soil particles. Nonspecific adsorption was substantial, irrespective of the soil used.
Shoe Allergens: Retrospective Analysis of Cross‐Sectional Data from the North American Contact Dermatitis Group, 2001‐2004

Background: Chemicals used in leather tanning, rubber processing, and/or adhesives are the most often‐cited culprits in footwear dermatitis. Patch testing patients with suspected shoe dermatitis is essential for diagnosis and management. Objectives: The four goals for this study were to (1) determine the frequency of allergens associated with a shoe source in North American Contact Dermatitis Group (NACDG) patients with footwear allergic contact dermatitis; (2) compare these results to allergen frequencies from other published studies; (3) quantify the number of shoe‐related reactions that were not identified with the NACDG standard series; and (4) identify relevant allergens not included on the NACDG standard series, based on data from other published studies. Methods: The NACDG patch‐tested 10,061 patients between 2001 and 2004. Data were retrospectively analyzed by (1) allergen source coded as “shoe,” (2) site of dermatitis as “feet,” and (3) diagnosis of “allergic contact dermatitis. ” Results: Among the 109 NACDG patients with allergic contact dermatitis (ACD) of the foot and a shoe source of allergens, ptertiary butylphenol formaldehyde resin, an adhesive, was the most common allergen, accounting for 24.7% of positive patch‐test results, followed by potassium dichromate (17.5%) and carba mix (11.7%). When the data were examined according to groups of allergens, rubber chemicals (40.4%) were the most frequent allergens, followed by adhesives (32.5%), and leather components (20.1%). When data from published studies were pooled, potassium dichromate (31.5%) was the most frequent allergen, followed by p‐tertiary butylphenol formaldehyde resin (17.1%) and cobalt chloride (12.9%). NACDG patients were statistically more likely to have positive patch‐test reactions to p‐tertiary butylphenol formaldehyde resin and statistically less likely to have a positive patch‐test reaction to potassium dichromate than patients represented in pooled data from past studies. Nineteen (17.4%) of the 109 NACDG patients with ACD of the foot and a shoe source of allergens were identified as having a shoe source of a relevant allergen not included in the NACDG standard series. Conclusions: In NACDG patients, the most common individual shoe allergen was p‐tertiary butylphenol formaldehyde resin. As a group, rubber chemicals were most common, a finding consistent with those of other studies.
Intracellular calcium clearance in Purkinje cell somata from rat cerebellar slices

1 The mechanisms governing the return of intracellular calcium (Ca2+i) to baseline levels following depolarization‐evoked [Ca2+]i rises were investigated in Purkinje cell somata using tight‐seal whole‐cell recordings and fura‐2 microfluorometry, for peak [Ca2+]i ranging from 50 nM to 2 μM. 2 Ca2+i decay was well fitted by a double exponential with time constants of 0.6 and 3 s. Both time constants were independent of peak [Ca2+]i but the contribution of the faster component increased with [Ca2+]i. 3 Thapsigargin (10 μM) and cyclopiazonic acid (50 μM) prolonged Ca2+i decay indicating that sarco‐endoplasmic reticulum Ca2+ (SERCA) pumps contribute to Purkinje cell Ca2+i clearance. 4 A modest participation in clearance was found for the plasma membrane Ca2+ (PMCA) pumps using 5,6‐succinimidyl carboxyeosin (40 μM). 5 The Na+‐Ca2+ exchanger also contributed to the clearance process, since replacement of extracellular Na+ by Li+ slowed Ca2+i decay. 6 Carbonyl cyanide m‐chlorophenylhydrazone (CCCP, 2 μM) and rotenone (10 μM) increased [Ca2+]i and elicited large inward currents at −60 mV. Both effects were also obtained with CCCP in the absence of external Ca2+, suggesting that mitochondrial Ca2+ uptake uncouplers release Ca2+ from intracellular stores and may alter the membrane permeability to Ca2+. These effects were irreversible and impeded tests on the role of mitochondria in Ca2+i clearance. 7 The relative contribution of the clearance systems characterized in this study varied as a function of [Ca2+]i. At 0.5 μM Ca2+i, SERCA pumps, PMCA pumps and the Na+‐Ca2+ exchanger contribute equally to removal and account for 78 % of the process. Only 45 % of the removal at 2 μM Ca2+i can be explained by these systems. In this high [Ca2+]i range the major contribution is that of SERCA pumps (21 %) and of the Na+‐Ca2+ exchanger (18 %), whereas the contribution of PMCA pumps is only 6 %.
Fibrinogen substitution improves whole blood clot firmness after dilution with hydroxyethyl starch in bleeding patients undergoing radical cystectomy: a randomized, placebo‐controlled clinical trial

Summary. Background: Infusion of artificial colloids such as hydroxyethyl starch (HES) induces coagulopathy to a greater extent than simple dilution. Several studies have suggested that the coagulopathy could be corrected by substitution with a fibrinogen concentrate. Objectives: The aims of the present prospective, randomized, placebo‐controlled trial were to investigate the hemostatic effect of a fibrinogen concentrate after coagulopathy induced by hydroxyethyl starch in patients experiencing sudden excessive bleeding during elective cystectomy. Methods: Twenty patients were included. Blood loss was substituted 1:1 with HES 130/0.4. At a dilution level of 30%, patients were randomly selected for intra‐operative administration of a fibrinogen concentrate or placebo. The primary endpoint was maximum clot firmness (MCF), as assessed by thromboelastometry. Secondary endpoints were blood loss and transfusion requirements, other thromboelastometry parameters, thrombin generation and platelet function. Results: Whole‐blood MCF was significantly reduced after 30% dilution in vivo with HES. The placebo resulted in a further decline of the MCF, whereas randomized administration of fibrinogen significantly increased the MCF. Furthermore, only 2 out of 10 patients randomly chosen to receive fibrinogen substitution required postoperative red blood cell transfusions, compared with 8 out of 10 in the placebo group (P = 0.023). Platelet function and thrombin generation were reduced after 30% hemodilution in vivo, and fibrinogen administration caused no significant changes. Conclusions: During cystectomy, fluid resuscitation with HES 130/0.4 during sudden excessive bleeding induces coagulopathy that shows reduced whole‐blood maximum clot firmness. Randomized administration of fibrinogen concentrate significantly improved maximum clot firmness and reduced the requirement for postoperative transfusion.
Transcriptional activation of the NF‐κB p65 subunit by mitogen‐ and stress‐activated protein kinase‐1 (MSK1)

Nuclear factor κB (NF‐κB) is one of the key regulators of transcription of a variety of genes involved in immune and inflammatory responses. NF‐κB activity has long been thought to be regulated mainly by IκB family members, which keep the transcription factor complex in an inactive form in the cytoplasm by masking the nuclear localization signal. Nowadays, the importance of additional mechanisms controlling the nuclear transcription potential of NF‐κB is generally accepted. We show that the mitogen‐activated protein kinase inhibitors SB203580 and PD98059 or U0126, as well as a potent mitogen‐ and stress‐ activated protein kinase‐1 (MSK1) inhibitor H89, counteract tumor necrosis factor (TNF)‐mediated stimulation of p65 transactivation capacity. Muta tional analysis of p65 revealed Ser276 as a target for phosphorylation and transactivation in response to TNF. Moreover, we identified MSK1 as a nuclear kinase for p65, since MSK1 associates with p65 in a stimulus‐dependent way and phosphorylates p65 at Ser276. This effect represents, together with phosphorylation of nucleosome components such as histone H3, an essential step leading to selective transcriptional activation of NF‐κB‐dependent gene expression.
The politics of research on farmer-managed irrigation systems in Asia : Some reflections for Africa.

This article presents a reconstruction of the 1980s' research-policy debate on farmer-managed irrigation systems (FMIS) in Asia. Such a reconstruction yields important lessons for the role of academic researchers in the current research-policy debate on African farmer-led irrigation development (FLID). Two interrelated insights stand out: (1) academic irrigation research was (and is) produced in an institutional context that is infused with the politics of the professional tradition in irrigation, and more specifically, (2) academic knowledge on the institutional heterogeneity of farmer-organized irrigation was (and is) incompatible with how things really work in the institution of the irrigation tradition. These insights raise critical questions on the politics of academic research on FLID, whose research agenda is really pursued, what roles do academic researchers want to play, and how to make irrigation research in development more democratic?
5C-5 A Rigid Wall Approach to Physiologic Motion Rejection in Arterial Radiation Force Imaging

Physiologic motion corrupts measurements of induced tissue displacements and obscures tissue mechanical properties in radiation force ultrasound. Wall dilation and contraction with cardiac pulsation is especially disruptive to radiation force imaging the arterial system. We hypothesize that exploiting a rigid arterial wall model, which assumes long wavelength arterial pulse waves, will improve physiologic motion rejection in arterial radiation force imaging. Three rigid wall assuming filters (polynomial regression, principal component regression, and FIR high-pass filters) were compared to four filters that did not assume a rigid arterial wall (linear regression, quadratic regression, principal component regression, and FIR high-pass filters). The filters were tested using Field II generated data inclusive of simulated arterial wall motion combined with experimental acoustic radiation force impulse (ARFI) or shear wave elastography imaging (SWEI) displacement profiles. Performance metrics were sum of absolute differences (SAD) between original and filtered ARFI or SWEI displacement profiles in terms of total profile error, measured peak displacement error, measured recovery time error, and time-to-peak displacement error. Rigid wall assuming polynomial and principal component regression filters yielded the lowest SAD scores. The filters were also qualitatively compared on in vivo ARFI and SWEI data acquired in healthy pig iliac arteries.
Motion estimation in video coding using simplified optical flow technique

We propose an interpolation-free sub-pixel Motion Estimation (ME) technique that particularly aims at providing accurate Motion Vectors (MVs), where conventional sub-pixel interpolation ME algorithms used in video coding are too complex and time consuming. The proposed algorithm is a combination of block matching algorithms and simplified optical flow, which is Taylor approximation. The technique does not require any pixel interpolation and it is much faster than conventional ME methods. Statistical results illustrate that the new technique performs quickly and accurately with a compatible performance with respect to the benchmarking full search algorithm.
Preceptors' Use of Reflection to Teach in Ambulatory Settings: An Exploratory Study

Purpose Reflection on one's teaching behavior is a means to question teaching events to bring teaching actions to a conscious level, to interpret the consequences of those actions, and to conceptualize alternative teaching actions. Ambulatory teaching settings are variable, unpredictable, and discontinuous, often resulting in lessfocused teaching. The authors sought to measure the level of reflection on teaching used by preceptors to plan teaching in these settings. Method Three preceptors who had participated in the Case Western Reserve University's peer-coaching program each answered four questions about how they planned to respond to two teaching case studies. The questions were posed by a medical educator who, for three of the four questions, also prompted the preceptors to stimulate their reflection. The audiotaped responses were assessed using Sparks-Langer and Colton's framework for reflective thinking. Results The levels of reflective thinking increased after prompting, but they did not exceed the rather low technical and practical levels, particularly for the more complex of the two cases. Conclusion This exploratory intervention suggests that faculty rely more on external and non-reflective levels of thought when planning to teach in the ambulatory setting. The authors recommend further research to foster discussions about the cognitive processes involved in planning for teaching in this setting.
Design of Data-Driven Mathematical Laws for Optimal Statistical Classification Systems

This article will devise data-driven, mathematical laws that generate optimal, statistical classification systems which achieve minimum error rates for data distributions with unchanging statistics. Thereby, I will design learning machines that minimize the expected risk or probability of misclassification. I will devise a system of fundamental equations of binary classification for a classification system in statistical equilibrium. I will use this system of equations to formulate the problem of learning unknown, linear and quadratic discriminant functions from data as a locus problem, thereby formulating geometric locus methods within a statistical framework. Solving locus problems involves finding equations of curves or surfaces defined by given properties and finding graphs or loci of given equations. I will devise three systems of data-driven, locus equations that generate optimal, statistical classification systems. Each class of learning machines satisfies fundamental statistical laws for a classification system in statistical equilibrium. Thereby, I will formulate three classes of learning machines that are scalable modules for optimal, statistical pattern recognition systems, all of which are capable of performing a wide variety of statistical pattern recognition tasks, where any given M-class statistical pattern recognition system exhibits optimal generalization performance for an M-class feature space.
Evanescent Field Biosensor Using Polymer Slab Waveguide-Based Cartridges for the Optical Detection of Nanoparticles

We present a polymer optical waveguide integration technology for the detection of nanoparticles in an evanescent field (EF)-based biosensor. Polymer waveguides together with their light coupling structures are designed to be integrated in a novel cartridge concept which will eventually lead to cost-effective, rapid, and easy-to-use point-of-care testing (POCT). The selected slab waveguides generate a homogeneous and well-defined EF, illuminating magnetic nanoparticles that are used as optical contrast labels and are measured using dark-field microscopy. The nanoparticles quantitatively bind to the sensor surface in the presence of target molecules, mediated by antibodies. Compatibility of the waveguide materials with these biomolecules is therefore a strong requirement. When designing a biosensor for POCT, it is also necessary to consider fabrication and manipulation tolerances, targeting the compatibility with mass-production technologies. In this context, polymer optics offer unique advantages, and in combination with the optical contrast labels a very high sensitivity can be achieved. The sensing concept was assessed by comparing various commercially available polymer materials (LightLink, Ormocer, Epocore/Epoclad) in terms of waveguide design and fabrication, optical performance (detection of nanoparticles), and biological compatibility and performance as a sensor surface in an immuno-assay for cardiac troponin I.
Purification, characterization, and cloning of a heme-binding protein (23 kDa) in rat liver cytosol.

A heme-binding protein (designated HBP23) has been purified from rat liver cytosol using heme-affinity chromatography and either reverse-phase high-performance liquid chromatography or sequential ion-exchange chromatography. The protein (23 kDa) binds heme with an affinity (Kd = 55 nM) higher than that of the abundant cytosolic heme-binding proteins, heme-binding protein (HBP)/liver fatty acid-binding protein (L-FABP) and the glutathione S-transferases (GSTs) (Kd = 100-200 nM). HBP23 is present in the cytosol of liver, kidney, spleen, small intestine, and heart, with the liver showing the highest content. A cDNA coding the 23-kDa protein was cloned using reverse transcription polymerase chain reaction with degenerative oligonucleotides derived from partial amino acid sequences. The cloned cDNA encoded 199 amino acids, and its amino acid sequence showed no homology to HBP/L-FABP, GSTs, or any other heme-binding proteins or hemeproteins. Homology search showed that HBP23 is highly homologous to mouse macrophage 23-kDa stress protein, which is inducible by oxidant stress in peritoneal macrophages [Ishii, T. , Yamada, M. , Sato, H. , Matsue, M. , Taketani, S. , Nakayama, K. , Sugita, Y. , and Bannai, S. (1993) J. Biol. Chem. 268, 18633-18636]. Thioredoxin peroxidase as well as HBP23 and the mouse macrophage 23-kDa stress protein are members of the peroxiredoxin family, a recently recognized class of antioxidant proteins [Chae, H. Z. , Chung, S. J., & Rhee, S. G. (1994) J. Biol. Chem. 269, 27670-27678]. An increase in HBP23 mRNA was observed in Hepa 1-6 cells after treatment with heme and cadmium and during liver regeneration after partial hepatectomy. (ABSTRACT TRUNCATED AT 250 WORDS)