Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonuniform Behavior of Intravenous Anesthetics on Postischemic Adhesion of Neutrophils in the Guinea Pig Heart

Adhesion of polymorphonuclear neutrophils (PMN) to the coronary endothelium is a crucial step in the development of ischemic myocardial injury. We tested the possible effects of six widely used IV anesthetics on non- and postischemic coronary adhesion of PMN in isolated perfused guinea pig hearts. Hearts (n = 5–11/group) were perfused under conditions of constant coronary flow. After 15 min global warm ischemia, PMN (106) were infused in the second minute of reperfusion. The number of cells reemerging in the coronary effluent within 2 min was expressed as a percentage of the total number of administered PMN. Anesthetics were given 20 min before ischemia and during reperfusion. In addition, the ability of the drugs to influence the oxidative burst reaction of PMN was assessed by measuring luminol-enhanced chemiluminescence in response to 0.1 &mgr;M N-formyl-l-methionyl-l-leucyl-l-phenylalanine. Under nonischemic conditions, 26.3% ± 0.5% of the injected PMN did not acutely reemerge from the coronary system. Subjecting the hearts to ischemia augmented retention to 40.0% ± 1.6% (P < 0.05). This postischemic stimulation of adhesion was fully prevented by ketamine (10 &mgr;M: 22.8% ± 1.6%, 20 &mgr;M: 26.6% ± 0.7%), thiopental (25 &mgr;M: 24.0% ± 1.7%, 50 &mgr;M: 24.0% ± 1.4%), and midazolam (1.5 &mgr;M: 29.0% ± 0.9%, 3 &mgr;M: 26.4% ± 1.4%). Propofol also inhibited the augmented postischemic retention at 25 &mgr;M (28.7% ± 2.4%). However, 50 &mgr;M propofol, etomidate (0.5 and 1 &mgr;M), and fentanyl (1 &mgr;M) all had no effect. Only thiopental reduced the nonischemic adhesion value (14.0% ± 3.7%). This may be linked to the direct antioxidative action of thiopental (50% reduction in oxidative burst activity). Whereas ketamine, midazolam, and propofol did not significantly influence oxidant production by PMN, etomidate and the lipid solvent Intralipid enhanced the burst reaction. This activating effect of the lipid component could explain the biphasic behavior of propofol emulsion. Despite some possible differences in efficacy, several IV anesthetics may protect the heart from PMN-mediated reperfusion injury. Implications Ketamine, thiopental, and midazolam, but not etomodate or fentanyl, reduce postischemic adhesion of neutrophils in the coronary system of isolated perfused guinea pig hearts, suggesting a role in mitigating myocardial reperfusion injury.
Stability of distributed LMS under cooperative stochastic excitation

Distributed estimation algorithms can estimate a dynamic process of interest by a set of estimators cooperatively, when any individual estimator cannot. The paper considers this kind of problems and focuses on a class of distributed least mean-square(LMS) algorithms in discrete time. Stability analysis will be provided under a weakest possible cooperative stochastic excitation condition. We remark that the stringent conditions such as independency and stationarity that have been used in almost all the existing literatures are no longer used in this paper. In addition, a simulation result comparing with the non-cooperative LMS algorithm will be provided to show the advantage of the distributed LMS algorithm studied in the paper.
Role of GM1 binding in the mucosal immunogenicity and adjuvant activity of the Escherichia coli heat‐labile enterotoxin and its B subunit

Escherichia coli (E. coli ) heat‐labile toxin (LT) is a potent mucosal immunogen and immunoadjuvant towards co‐administered antigens. LT is composed of one copy of the A subunit, which has ADP‐ribosylation activity, and a homopentamer of B subunits, which has affinity for the toxin receptor, the ganglioside GM1. Both the ADP‐ribosylation activity of LTA and GM1 binding of LTB have been proposed to be involved in immune stimulation. We investigated the roles of these activities in the immunogenicity of recombinant LT or LTB upon intranasal immunization of mice using LT/LTB mutants, lacking either ADP‐ribosylation activity, GM1‐binding affinity, or both. Likewise, the adjuvant properties of these LT/LTB variants towards influenza virus subunit antigen were investigated. With respect to the immunogenicity of LT and LTB, we found that GM1‐binding activity is essential for effective induction of anti‐LTB antibodies. On the other hand, an LT mutant lacking ADP‐ribosylation activity retained the immunogenic properties of the native toxin, indicating that ADP ribosylation is not critically involved. Whereas adjuvanticity of LTB was found to be directly related to GM1‐binding activity, adjuvanticity of LT was found to be independent of GM1‐binding affinity. Moreover, a mutant lacking both GM1‐binding and ADP‐ribosylation activity, also retained adjuvanticity. These results demonstrate that neither ADP‐ribosylation activity nor GM1 binding are essential for adjuvanticity of LT, and suggest an ADP‐ribosylation‐independent adjuvant effect of the A subunit.
Interaction of Purulent Material with Antibiotics Used to Treat Pseudomonas Infections

To define factors contributing to the adverse prognosis of patients with gram-negative bacillemia and abscess formation, we studied the interaction between polymyxin B, colistin sulfate, gentamicin, or carbenicillin with purulent material. Carbenicillin activity was not significantly altered by incubation with pus. Equal volumes of antibiotic and purulent sediment decreased the effective concentration of polymyxin B, colistin sulfate, or gentamicin from 100 μg/ml to 3 to 6 μg/ml. One milliliter of purulent sediment bound more than 700 μg of gentamicin and 1,500 μg of polymyxin B or colistin sulfate. This effect occurred rapidly, proceeded at 4 and 37 C, was stable for 24 to 48 h, and was altered, but not abolished, by varying the pH of the solution. Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation.
Comparison of Breast and Abdominal Adipose Tissue Mesenchymal Stromal/Stem Cells in Support of Proliferation of Breast Cancer Cells

In this study, we compared MSCs from breast and abdominal tissue in terms of their expression of genes deemed important in the support of breast cancer growth and their effect on gene profile of macrophages after coculture. In addition, we investigated the role of MSCs, alone or in combination with macrophages, on proliferation of breast cancer cell lines. Our results show that MSCs derived from breast and abdominal adipose tissues have a comparable gene expression profile, have similar effect on gene expression of macrophages, and are comparable in supporting breast cancer cell line proliferation.
Plasma adiponectin concentration has an inverse and a non linear association with estimated glomerular filtration rate in patients with K/DOQI 3 - 5 chronic kidney disease.

BACKGROUND Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). A few studies have demonstrated elevated plasma adiponectin and leptin levels in CKD. The aims of this study were to assess whether 1) estimated glomerular filtration rate (eGFR) is associated with plasma leptin and adiponectin; and 2) adiponectin and leptin (partly) explain associations of CKD with endothelial dysfunction, insulin resistance, and low-grade inflammation in patients with K/DOQI Stage 3 - 5 CKD. METHODS Baseline data from 91 patients with Stage 3 - 4 CKD in the anti-oxidant therapy in chronic renal insufficiency study, a randomized, double-blind, placebo-controlled trial, in which the effects of oxidative stress-lowering treatment on vascular function and structure were studied, and from 50 dialysis naïve patients, who took part in an open-label, randomized study that compared two peritoneal dialysis regimens, used in the analysis. All subjects for both the studies were recruited in the same centres. RESULTS The association between eGFR and adiponectin was non-linear. In multivariate analysis, log-eGFR (unstandardized beta = 8.303 microg/ml, p < 0.0001) was the strongest determinant of adiponectin, and body mass index the strongest determinant of leptin (beta = 2.477 ng/ml, p < 0.0001). Plasma adiponectin and leptin did not modify the associations between eGFR and plasma von Willebrand factor or soluble vascular adhesion molecule-1. Plasma leptin had the strongest association with the homeostatic model assessment (HOMA-IR) index. Plasma C-reactive protein had no association with adiponectin or leptin. CONCLUSIONS In patients with K/DOQI Stage 3 - 5 CKD, renal function had a significant non-linear inverse association with and was the strongest predictor of adiponectin. BMI was the strongest predictor of plasma leptin. Plasma adiponectin and leptin did not explain, and thus presumably are not involved in, the association between eGFR and some markers of endothelial dysfunction.
Familial predisposition to thyroid disease in Down's syndrome: controlled immunoclinical studies.

Extra twenty-first chromosomal material is now known to be the immediate cause of Down's syndrome (mongolism) [1], but primary etiologic mechanisms have not yet been firmly demonstrated. One possibility is that a factor related to thyroid autoimmunity in a mother predisposes her to having a child with a chromosomal aberration such as is seen in Down's syndrome (see [2] for review). The increased frequency of thyroid disease in mothers of subjects with Down's syndrome reported in many older studies (e.g., [3-5]) is compatible with this hypothesis. One criticism frequently leveled against the older studies is that no consistent maternal thyroid abnormalities were found, but this clinical variability would not be a surprising finding in a group of women with thyroid autoimmunity since the clinical manifestations may be extremely varied. More compelling criticisms of some of these studies are that they were poorly controlled and that the diagnoses of maternal thyroid disease were based solely on the families' responses to questionnaires without further verification. Consequently, we initiated a controlled study of thyroid disease in families whose children with Down's syndrome were living at home. Preliminary results suggested an increased frequency of thyroid disease in mothers and maternal relatives (Fialkow et al., cited in [6]). To assess the significance of those preliminary findings, the original Home Study was expanded and a study of families with institutionalized children was carried out. We report here the results of both the Home and the Institution Studies.
Repetitive control system: a new type servo system for periodic exogenous signals

A control scheme called repetitive control is proposed, in which the controlled variables follow periodic reference commands. A high-accuracy asymptotic tracking property is achieved by implementing a model that generates the periodic signals of period L into the closed-loop system. Sufficient conditions for the stability of repetitive control systems and modified repetitive control systems are derived by applying the small-gain theorem and the stability theorem for time-lag systems. Synthesis algorithms are presented by both the state-space approach and the factorization approach. In the former approach, the technique of the Kalman filter and perfect regulation is utilized, while coprime factorization over the matrix ring of proper stable rational functions and the solution of the Hankel norm approximation are used in the latter one. >
Transcutaneous vagus nerve stimulation in tinnitus: a pilot study

Abstract Conclusions: This pilot study shows that transcutaneous vagus nerve stimulation (tVNS), if combined with sound therapy (ST), reduces the severity of tinnitus and tinnitus-associated distress. Our magnetoencephalography (MEG) results show that auditory cortical activation can be modulated by the application of tVNS. Thus, tVNS might offer a new avenue to treat tinnitus and tinnitus-associated distress. Objectives: Recent studies suggest that tinnitus can be improved by tailored ST or by VNS plus ST. Our aims were to study whether tVNS has therapeutic effects on patients with tinnitus and, additionally, if tVNS has effects on acoustically evoked neuronal activity of the auditory cortex. Methods: The clinical efficacy was studied by a short-term tVNS plus ST trial in 10 patients with tinnitus using disease-specific and general well-being questionnaires. tVNS was delivered to the left tragus. The acute effects of tVNS were evaluated in eight patients in the MEG study in which the N1m response was analyzed in terms of source level amplitude and latency in the presence or absence of tVNS. Results: The treatment with tVNS plus ST produced improved mood and decreased tinnitus handicap scores, indicating reduced tinnitus severity. The application of tVNS decreased the amplitude of auditory N1m responses in both hemispheres.
Age‐Related Alterations in the Lymphohematopoietic and B‐Lineage Precursor Populations in NZB Mice

Significant disturbances in B lineage populations of New Zealand Black (NZB) mice have been reported, both with respect to their phenotypes as well as to their function. Notably, there is a profound age‐dependent decrease in B‐cell precursors in this strain of lupus prone mice. In efforts to characterize the impact of this disturbance in disease, we performed an intensive phenotypic and B‐cell population analysis in young and old NZB mice. Our results revealed that there was a significant age‐dependent decrease in B cell precursors at all levels of the B‐cell‐lineage developmental pathway. Analysis of the proliferative capacity of these cell populations showed a comparative decrease in cycling activity in the B‐cell‐lineage populations of old NZB mice. Furthermore, these cell subsets were much more susceptible to spontaneous apoptosis when compared with similar populations from age‐matched BALB/c or young NZB mice. Since the frequency of cells that express the interleukin‐7 receptor (IL‐7R) declines as NZB mice age, we hypothesize that impairment of IL‐7R signal transduction pathways could contribute to severe perturbations of B‐cell function in aged NZB mice.
Hemorheology, sickle cell trait, and alpha-thalassemia in athletes: effects of exercise.

PURPOSE This study investigated hemorheological parameters in response to exercise in sickle cell trait (SCT) athletes with or without alpha-thalassemia METHODS Six athletes with SCT (HbAS), 7 athletes with SCT and alpha-thalassemia (HbASAT), and 10 control athletes (HbAA) performed a progressive and maximal exercise test on cycloergometer. Blood viscosity (etab), plasma viscosity (etap), etab at corrected hematocrit (etab45), hematocrit (Hct), and red blood cell (RBC) rigidity were assessed at rest, at maximal exercise and 24 h after exercise RESULTS etab and etap were not different between the three groups at any time. Exercise induced changes in etab in HbAA and HbASAT groups but not in HbAS group. etab45 was higher in HbAS group compared with the other groups (P < 0.05), at rest and 24 h after exercise and increased only in HbAA group in response to exercise. HbAS group had lower Hct than HbAA group at any time. Hct and etap increased after exercise and declined under baseline values 24 h after exercise in all groups. RBC rigidity was higher in HbAS group compared with HbAA and HbASAT groups at any time, and was lower and higher at maximal exercise and 24 h after exercise, respectively, in all groups compared with resting values CONCLUSIONS These results demonstrate that HbAS group is prone to higher RBC rigidity, which might lead to hemorheological alterations that are thought to participate to microcirculation disorders. However, these alterations are limited by the coexistence of alpha-thalassemia. Moreover, hemorheological parameters were not further impaired in SCT athletes with or without alpha-thalassemia in response to exercise. Training status might be protective from physiological stresses usually leading to sickling process in SCT carriers.
Urea in sugarcane-based diets for dairy cows

We evaluated the effect of adding four levels (0, 4, 8 and 12 g/kg, as fed) of a mixture (9:1) of urea and ammonium sulfate (UAs) to sugarcane on feed intake and digestibility, productive performance and metabolism of nitrogen compounds of dairy cows. Twelve multiparous Holstein cows (12.6±0.5 kg/d of milk, 225±90 days in milk) were distributed in three 4 × 4 Latin squares, receiving diets with the same amount of nitrogen (125 g crude protein/kg of dry matter). Concentrate feed was supplied at a ratio of 1 kg for each 3 kg of milk produced. The sugarcane presented 21.9 oBrix. The level of UAs did not affect intake, total digestibility of diet components, milk production or milk components. Increasing UAs level linearly increased concentration of plasma urea nitrogen (PUN), urinary excretion of nitrogen and contribution of non-urea nitrogen in the urinary excretion and linearly reduced milk production/urinary excretion of nitrogen ratio. In spite of the linear increase of PUN with increased urea, the maximum value observed (14.31 mg/dL) was below the threshold value of 20 mg/dL, above which reproductive function may be compromised. In diets with sugarcane for dairy cows with production below 15 kg/day, the UAs level may be raised from 0 to 12 g/kg natural matter without impairing performance.
Fluorescence fingerprints of Eisenia fetida and Eisenia andrei ¶

We describe a fluorescent method that allows to differentiate the worms Eisenia fetida and Eisenia andrei. In fact, the coelomic fluid of E. andrei displays specific fluorescence absent in that of E. fetida. The two species do not metabolize the same types of molecules and thus can be differentiated at the molecular level. Each species has specific fluorescence fingerprints.
Use of temperature-sensitive mutants to study gene expression during sporulation in Bacillus subtilis

Two temperature-sensitive sporulation mutants have been characterized. One mutant, which is blocked at stage II, has a short temperature-sensitive period that occurs at about the time when the spore septum is formed. Cells can escape the sporulation block, if incubated for a short period at the permissive temperature, but are prevented from doing so by inhibitors of transcription and translation; this suggests that the product of the defective gene is a protein and that the messenger ribonucleic acid which codes for this protein is short-lived. The other mutant is blocked at stage IV to V and has a long temperature-sensitive period that starts during stage III and precedes the stage at which the mutational defect is phenotypically expressed. The behavior of this mutant in temperature-shift experiments suggests that synthesis of the product of the defective gene commences long before it assumes its physiological function.
Exhaled Nitric Oxide and Aeroallergen Sensitization in Asthmatic Children

Snežana Živanović1,2, Ljiljana Šaranac1,2, Bojko Bjelaković1,2, Slobodanka Petrović3 and Zorica Živković4,5 1Clinic of Paediatrics, Clinical Center Nis, Serbia 2Medical Faculty, University of Nis, Serbia 3Institute for Child and Youth Health Care of Vojvodina, Paediatric Clinic, Department of Pulmonology, Novi Sad, Serbia 4Children's Hospital for Lung Diseases and Tuberculosis, Medical Center "Dr Dragiša Mišović", Belgrade, Serbia 5Faculty of Pharmacy Novi Sad, Serbia
In vitro interaction between components of the inner membrane complex of the maltose ABC transporter of Escherichia coli : modulation by ATP

Interactions between domains of ATP‐binding cassette (ABC) transporters are of great functional importance and yet are poorly understood. To gain further knowledge of these protein–protein interactions, we studied the inner membrane complex of the maltose transporter of Escherichia coli. We focused on interactions between the nucleotide‐binding protein, MalK, and the transmembrane proteins, MalF and MalG. We incubated purified MalK with inverted membrane vesicles containing MalF and MalG. MalK bound specifically to MalF and MalG and reconstituted a functional complex. We used this approach and limited proteolysis with trypsin to show that binding and hydrolysis of ATP, inducing conformational changes in MalK, modulate its interaction with MalF and MalG. MalK in the reconstituted complex was less sensitive to protease added from the cytoplasmic side of the membrane, and one proteolytic cleavage site located in the middle of a putative helical domain of MalK was protected. These results suggest that the putative helical domain of the nucleotide‐binding domains is involved, through its conformational changes, in the coupling between the transmembrane domains and ATP binding/hydrolysis at the nucleotide‐binding domains.
Correlation of molecular effects and pathologic complete response to preoperative lapatinib and trastuzumab, separately and combined prior to neoadjuvant breast cancer chemotherapy.

506 Background: Extinction of HER2 signaling in HER2 driven BC may be curative. Alternative activation pathways (HER1, HER3) & mutated downstream signal transducers allow resistance to therapy. STUDY AIM molecularly characterize HER2+ BC before & after 2 wks anti-HER2 therapy (AHT) with T, L, or T+L & to correlate these with pCR to continuation of same AHT with neoadjuvant chemo (FEC75 x 4 Q3W->Paclitaxel x 12W). pCR is absence of all invasive cancer in breast & lymph nodes. pCR-Breast used for molecular analysis. METHODS 100 consenting patients (pts) with stage II/III, HER2+ BC, normal cardiac function were randomized to T, L or T+L. Before & after AHT, all pts had core needle biopsies for tissue microarray, stem cell analysis & reverse phase protein microarrays, measuring 60 different phosphoprotein/post-translationally modified protein signaling & gene expression analysis endpoints. RESULTS pCR in the ITT-E (ITT-E: Pts who had surgery, ≥75% compliant to chemo and took no prohibited meds.) pts: 54%, 45%, 74% for T, L, T+L arms. Analysis by response: 1) Responders (R) have altered HER2 downstream interconnections with PI3K (Spearman rho correlation [rho] 0.5, p=0.12) vs the non-responders [NR] (rho 0.9, p=0.037) & HER3Y1289 correlated (p<0.001 for all endpoints) with EGFRy1173, mTOR 2448, & Beta Catenin 33. 2) NR have a) intact signaling with PI3K (rho 0.9, p=0.037); b) intact interactions with autophagy (PI3K - LC3B rho 0.83, p=0.04); c) intact stem cell - proliferation signaling (Musashi - p70S6 Kinase T389 (p=0.007, rho 0.89), CD44 - PTEN S380 (p<0.001, rho 0.92) were not significant in R. Analysis by AHT, prior to AHT R vs. NR: 1) TRZ MMP-14, 2) LAP EGFRtyr1068 & Fox01/03T24/32 were statistically different. CONCLUSIONS Our study provides a unique in vivo snapshot of molecular changes in signaling pathways of microdissected tumor cells before & after anti-HER2 therapy. Molecular profiles suggest NR use autophagy & stem cell related pathways to evade therapy, while R have disruption of HER2-HER3 linkages & known downstream regulators of growth & transcription. These results provide insights into novel candidate "drugable" targets.