Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence of C4d Stain in Protocol Biopsies from Renal Allografts: Results from a Multicenter Trial

C4d staining of renal allografts is regarded as an in situ marker of active humoral rejection. Few data are available about the incidence of C4d deposition in protocol biopsies compared to indication biopsies. To evaluate whether center‐specific factors influence the incidence of C4d detection, we performed a multicenter study. From three European centers, 551 protocol and 377 indication biopsies were reclassified according to the updated Banff criteria and stained for C4d. C4d results were recorded as diffuse or focal positive and statistically correlated to clinical parameters, morphology and graft survival. In the protocol biopsies, a diffuse C4d stain was found in 2.0%, and a focal stain in 2.4%. In indication biopsies, 12.2% were diffusely and 8.5% focally C4d positive (protocol:indication p < 0.0001). The incidence of C4d deposition varied significantly between centers, attributable to variable numbers of presensitized patients with more C4d positive indication and protocol biopsies. Diffuse and focal C4d stain correlated with morphology of humoral rejection in protocol as well as in indication biopsies. Protocol biopsies show a significantly lower incidence of C4d deposition than indication biopsies. Subclinical C4d detection in protocol biopsies had no significant impact on allograft survival in our series.
Spatial profile of dendritic calcium transients evoked by action potentials in rat neocortical pyramidal neurones.

1. Simultaneous measurements of intracellular free calcium concentration ([Ca2+]i) and intrasomatic and intradendritic membrane potential (Vm) were performed using fura‐2 fluorimetry and whole‐cell recording in neocortical layer V pyramidal neurones in rat brain slices. 2. Back‐propagating action potentials (APs) evoked [Ca2+]i transients in the entire neurone including the soma, the axon initial segment, the apical dendrite up to the distal tuft branches, and the oblique and basal dendrites, indicating that following suprathreshold activation the entire dendritic tree is depolarized sufficiently to open voltage‐dependent calcium channels (VDCCs). 3. The [Ca2+]i transient peak evoked by APs showed large differences between various compartments of the neurone. Following a single AP, up to 6‐fold differences were measured, ranging from 43 +/‐ 14 nM in the soma to 267 +/‐ 109 nM in the basal dendrites. 4. Along the main apical dendrite, the [Ca2+]i transients evoked by single APs or trains of APs had the largest amplitude and the fastest decay in the proximal region; the [Ca2+]i transient peak and decay time constant following a single AP were 128 +/‐ 25 nM and 420 +/‐ 150 ms, respectively, and following a train of five APs (at 10‐12 Hz), 710 +/‐ 214 nM and 390 +/‐ 150 ms, respectively. The [Ca2+]i transients gradually decreased in amplitude and broadened in more distal portions of the apical dendrite up to the main bifurcation. 5. In the apical tuft branches, the profile of the [Ca2+]i transients was dependent on AP frequency. (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Remote Ischemic Preconditioning and Myocardial Ischemia on MicroRNA-1 Expression in the Rat Heart In Vivo

ABSTRACT Remote ischemic preconditioning (RIPC) is an easily applicable method for protecting the heart against a subsequent ischemia and reperfusion (I/R) injury. However, the exact molecular mechanisms underlying RIPC are unknown. We examined the involvement of microRNAs (miRNAs) and in particular the expression of miRNA-1 (miR-1) in RIPC and myocardial ischemia. Remote ischemic preconditioning was conducted by four cycles of 5-min bilateral hind-limb ischemia in male Wistar rats. Cardiac ischemia was induced by ligation of the left anterior descending coronary artery for 35 min followed by 2 or 6 h of reperfusion. MicroRNA expression was analyzed by Taqman miRNA arrays and quantitative polymerase chain reaction assays. Luciferase assays were performed to validate the miR-1 target gene brain-derived neurotrophic factor (BDNF). Brain-derived neurotrophic factor mRNA and protein levels were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Remote ischemic preconditioning led to a differential expression of miRNAs. The most abundant cardiac miRNA, miR-1, was downregulated by RIPC without following ischemia as well as after I/R and RIPC followed by I/R after 2 h of reperfusion. After 6 h of reperfusion, RIPC led to an upregulation of miR-1, whereas ischemia had no effect on miR-1 expression. Luciferase assays confirmed the interaction of miR-1 with BDNF, a protein that has been shown to exert cardioprotective effects. Brain-derived neurotrophic factor protein levels in rat hearts measured by enzyme-linked immunosorbent assay were not significantly altered after 2 or 6 h of reperfusion in all intervention groups. Remote ischemic preconditioning leads to changes in the expression levels of the most abundant cardiac miRNA, miR-1. MicroRNA 1 levels did not correlate with protein levels of BDNF, a known miR-1 target, in vivo. Further studies are needed to explore the biological significance of changes in miR-1 expression levels and the potential interaction with BDNF in RIPC-induced cardioprotection.
Long‐Term Depression in the Hippocampus In Vivo Is Associated with Protein Phosphatase‐Dependent Alterations in Extracellular Signal‐Regulated Kinase

Abstract: There is growing evidence that activation of either protein kinases or protein phosphatases determines the type of plasticity observed after different patterns of hippocampal stimulation. Because activation of the extracellular signal‐regulated kinase (ERK) has been shown to be necessary for long‐term potentiation, we investigated the regulation of ERK in long‐term depression (LTD) in the adult hippocampus in vivo. We found that ERK immunoreactivity was decreased following the induction of LTD and that this decrease required NMDA receptor activation. The LTD‐associated decrease in ERK immunoreactivity could be simulated in vitro via incubation of either purified ERK2 or hippocampal homogenates with either protein phosphatase 1 or protein phosphatase 2A. The protein phosphatase‐dependent decrease in ERK immunoreactivity was inhibited by microcystin. Intrahippocampal administration of the protein phosphatase inhibitor okadaic acid blocked the LTD‐associated decrease in ERK2, but not ERK1, immunoreactivity. Collectively, these data demonstrate that protein phosphatases can decrease ERK immunoreactivity and that such a decrease occurs with ERK2 during LTD. These observations provide the first demonstration of a biochemical alteration of ERK in LTD.
Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men.

BACKGROUND Exogenous glucagon-like peptide-1 (GLP-1) inhibits eating in healthy, overweight, and diabetic subjects. OBJECTIVE The GLP-1 receptor antagonist exendin(9-39)NH2 (ex9-39) was used to further explore the role of GLP-1 as an endogenous satiation signal. DESIGN Two double-blind, 4-way crossover studies were performed, each of which included 10 healthy men. In study A, subjects received an intravenous infusion of ex9-39 or saline plus an oral glucose preload and an intraduodenal infusion of saline or glucose for 60 min. In study B, intravenous infusions were identical, but an oral mixed-liquid meal preload and a 60-min intraduodenal infusion of saline or oleic acid were administered. Thirty minutes after oral preloads, subjects ate and drank ad libitum, and amounts ingested and the time to meal completion were quantified. In addition, appetite and plasma GLP-1, peptide YY (PYY), insulin, glucagon, and blood glucose concentrations were measured. RESULTS In both studies, GLP-1, PYY, and glucagon were substantially higher with intravenous ex9-39 than with intravenous saline (P ≤ 0.001). Insulin was lower with intravenous ex9-39 during intraduodenal glucose (P ≤ 0.05). The decrease in prospective food consumption and desire to eat during ad libitum eating after glucose ingestion was slightly attenuated (P ≤ 0.05 and P ≤ 0.01, respectively) with ex9-39. However, with intravenous ex9-39, food and fluid intakes and eating duration were not changed in either study. CONCLUSIONS GLP-1 receptor antagonism slightly modulates appetite during ad libitum eating, but food and fluid intakes and meal duration remain unchanged, suggesting that endogenous GLP-1 is a weak satiation signal. However, concomitant substantial increases in plasma PYY and glucagon may counteract a desatiating effect of ex9-39. The effect of ex9-39 on PYY secretion supports an autoinhibitory feedback mechanism that controls L cell secretion; the effect on insulin and glucagon confirms the role of GLP-1 in glycemic control through its action on pancreatic α and β cells.
Modelling and Enhancing Full-Duplex MAC for Single-Hop 802.11 Wireless Networks

Theoretically, full-duplex (FD) transmissions hold the promise of doubling the channel capacity. However, this capacity increase can not directly translate to the useful throughput at the medium access control (MAC) layer due to overheads. In this letter, we propose an enhanced full-duplex MAC (FD+) for improving the performance of wireless networks. We also present a simple analytic model for investigating what gains can be achieved at the MAC layer. The simple model for FD transmissions can accurately capture the new sub-scenarios of two-node simultaneous transmissions that are traditionally handled as collisions by IEEE 802.11 distributed coordination function (DCF). The performance of FD+ is compared with DCF, a plain FD (FD-Plain) scheme and an FD MAC (FD-MAC) scheme from the literature. The analytic and simulation results show that FD+ is able to provide an average factor of 2.3 and 1.3 throughput increase against FD-Plain and FD-MAC, respectively.
Cholesterol and Malondialdehyde Contents of Broiler-Chicken Meat Supplemented with Indigofera zolingeriana Top Leaf Meal

This research aimed to increase functional value of broiler-chicken meat containing high antioxidant and low cholesterol through substitution of soybean meal (SBM) with Indigofera zollingeriana top leaf meal (ILM). The experiment used 160 day old broiler chicken (Cobb strain). The experimental chicken were provided dietary treatments when they were 15-days old (initial body weight of 460.5±1.56 g/bird) and terminated on day 35. A completely randomized design (CRD) with four treatments and four replications and ten birds in each replication was used in this experiment. Dietary treatments were: R1= diet containing 20% soybean meal (SBM) without I. zollingeriana top leaf meal (ILM); R2= diet containing 16% SBM and 5.9% ILM; R3= diet containing 12% SBM and 11.8% ILM; R4= diet containing 8% SBM and 17.74% ILM. Variables measured were performances (feed consumption, body weight gain, and feed conversion) and the quality of broiler meat (cholesterol, fat content, and malondialdehyde [MDA] concentration). The results showed that supplementation of 17.74% ILM (R4) as the substitution of 60% soybean meal protein produced the same performances of broilers as those of control diet (R1). Supplementation of 11.8% ILM as the substitution of 40% soybean meal protein (R3) decreased meat cholesterol by 34.70%, meat fat content by 52.93%, and MDA concentration by 62.52%. The conclusion of this study was that supplementation of 17.74% ILM produced the same performances as that of control diet, increased antioxidant content of the meat, indicated by a lower MDA concentration, and decreased cholesterol, as well as fat content of broiler-chicken meat.
Un marxisme anglais. A propos d'une nouvelle interprétation du matérialisme historique

Le marxisme connaît deux « questions nationales », correspondant à la nation comme objet et comme cause des théories marxistes. D'une part il y a la question théorique et stratégique : quelle est l'importance du caractère national pour le développement d'un peuple, et quel rôle faut-il attribuer à la lutte des peuples pour l'auto-détermination comparée à la lutte des classes proprement dite ? D'autre part il y a un problème qui relève de la sociologie de la connaissance : dans quelle mesure les diverses formes du marxisme sont-elles empreintes des traditions nationales dans lesquelles elles prennent naissance ? Il est clair, pour le moins, que la prise de position sur la question nationale en ce premier sens est elle-même une question nationale au second sens. Les peuples divisés par les frontières nationales, tels les Polonais, ou intégrés avec d'autres peuples dans une unité nationale plus vaste, telle la monarchie double d'Autriche-Hongrie, sont aussi ceux où les marxistes se sont penchés le plus sur l'idée de la nation.
Heavy and light chain pairing of bivalent quadroma and knobs-into-holes antibodies analyzed by UHR-ESI-QTOF mass spectrometry

The quadroma antibody represents the first attempt to produce a bispecific heterodimeric IgG antibody by somatic fusion of 2 hybridoma cells each expressing monoclonal antibodies with distinctive specificities. However, because of random heavy and light chain pairing, the desired functional bispecific antibody represents only a small fraction of the protein produced. Subsequently, the knobs-into-holes (KiH) approach was developed to enforce correct heavy chain heterodimerization. Assuming equimolar expression of 4 unmodified chains comprising 2 heavy and 2 light chains, the statistical distribution of all paired combinations can be calculated. With equimolar expression as the goal, we transfected HEK cells with 1:1:1:1 plasmid ratios and analyzed the protein A affinity-purified antibodies from the quadroma and KiH approaches qualitatively and quantitatively with regard to the estimated relative amounts of the products using electrospray quadrupole time-of-flight mass spectrometry. Our results show that all expected species are formed, and that, within the methodological limits, the species distribution in the mixtures corresponds approximately to the statistical distribution.
Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of Pseudomonas aeruginosa

ABSTRACT Pseudomonas aeruginosa is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clinical strains of P. aeruginosa and to define the mechanism of liposome-bacterium interactions. Aminoglycosides were incorporated into liposomes, and the bactericidal efficacies of both free and liposomal drugs were evaluated. To define the mechanism of liposome-bacterium interactions, transmission electron microscopy (TEM), flow cytometry, lipid mixing assay, and immunocytochemistry were employed. Encapsulation of aminoglycosides into liposomes significantly increased their antibacterial activity against the resistant strains used in this study (MICs of ≥32 versus ≤8 μg/ml). TEM observations showed that liposomes interact intimately with the outer membrane of P. aeruginosa, leading to the membrane deformation. The flow cytometry and lipid mixing assays confirmed liposome-bacterial membrane fusion, which increased as a function of incubation time. The maximum fusion rate was 54.3% ± 1.5% for an antibiotic-sensitive strain of P. aeruginosa and 57.8% ± 1.9% for a drug-resistant strain. The fusion between liposomes and P. aeruginosa significantly enhanced the antibiotics' penetration into the bacterial cells (3.2 ± 2.3 versus 24.2 ± 6.2 gold particles/bacterium, P ≤ 0.001). Our data suggest that liposome-entrapped antibiotics could successfully resolve infections caused by antibiotic-resistant P. aeruginosa through an enhanced mechanism of drug entry into the bacterial cells.
Preparation of Novel Core-shell Nanoparticles as Non-viral Gene Delivery Vectors: Surface Charge, Particle size, and Morphology

The well-defined core-shell amphiphilic nanoparticles consisting of the poly(methyl methacrylate) (PMMA) cores surrounded by the modified chitosan shells were prepared via a surfactant-free emulsion graft-copolymerization of methyl methacrylate from an aqueous modified chitosan solution induced by a small amount of tert-butyl hydroperoxide. The PMMA-chitosan core-shell particles have an average particle diameter of approximately 200 nm and display highly positive surface charges (+70 mV). Transmission electron microscopic (TEM) images clearly reveal a well-defined core-shell morphology of the nanoparticles where the PMMA cores are coated with chitosan shells. The core-shell nanoparticles were investigated as novel carriers for gene delivery. The nanoparticle/plasmid DNA complexes were characterized with respect to their binding affinity, particle size, and zeta-potential.
Comparative pharmacology of the H 1 antihistamines

The United States National Library of Medicine defi nes the term pharmacokinetics as “the dynamic and kinetic mechanisms of exogenous chemical products, and the absorption, biotransformation, distribution, release, transport and elimination of drug substances according to their dosage and extent and rate of metabolism”. Although the effi cacy of the different H 1 antihistamines in the treatment of allergic patients is similar, even when comparing fi rstand second-generation drugs, they are very different in terms of chemical structure, pharmacology and toxic potential. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is important for the correct usage of such drugs, particularly in patients belonging to extreme age groups, pregnant women, or subjects with concomitant diseases. The current requirements of the different drug agencies for authorizing the introduction of a new medication have led to the availability of much more information on the pharmacokinetic and pharmacodynamic characteristics of the second-generation antihistamines than on their fi rstgeneration predecessors. It seems that this consideration alone would advise the more widespread use of these more modern antihistamines – in contrast to the evidence supplied by the current sales statistics, which show fi rstgeneration antihistamines to be much more widely used. Curiously, most of the pharmacological aspects of the new antihistamines are diffi cult to document, and remain largely unpublished – the only source for consultation being the summaries presented by the drug manufacturers at scientifi c congresses and meetings, or the famous
Endostatin Inhibits Human Tongue Carcinoma Cell Invasion and Intravasation and Blocks the Activation of Matrix Metalloprotease-2, -9, and -13*

Endostatin, a 20-kDa collagen XVIII fragment, inhibits angiogenesis and tumor growth in vivo, but the mechanisms are still unclear. Matrix metalloproteases (MMPs), a family of extracellular and membrane-associated endopeptidases, collectively digest almost all extracellular matrix and basement membrane components, and thus play an important role in tumor progression. We studied the effects of recombinant human endostatin on human MMP-2, -9, -8, and -13. We found that endostatin inhibited the activation and catalytic activity of pro-MMP-9 and -13 as well as recombinant pro-MMP-2. It prevented the fragmentation of pro-MMP-2 that was associated with reduction of catalytic activity. Endostatin had no effect on MMP-8 as shown by collagenase activity assays. An in vitro migration assay and an in vivo chicken chorioallantoic membrane intravasation assay with the human tongue squamous cell carcinoma cell line HSC-3 revealed the biphasic nature of endostatin; low endostatin concentrations inhibited intravasation and migration of these cells in a dose-dependent manner, but at increased concentrations, the inhibitory effect was far less efficient. The results show that endostatin blocks the activation and activities of certain tumor-associated pro-MMPs, such as pro-MMP-2, -9, and -13, which may explain, at least in part, the antitumor effect of endostatin. Our results also suggest that endostatin inhibits tumor progression by directly affecting the tumor cells and not just acting via endothelial cells and blockage of angiogenesis.
21-kV SiC BJTs With Space-Modulated Junction Termination Extension

We report here 20-kV-class small-area (0.035 mm2) 4H-SiC bipolar junction transistors. We implemented edge termination techniques featuring two-zone junction termination extension and space-modulated rings. On-state characteristics showed a current gain of 63 and a specific on-resistance of 321 mΩ·cm2, which is slightly below the SiC unipolar limit. We achieved the open-base blocking voltage of 21 kV at a leakage current of 0.1 mA/cm2, which is the highest blocking voltage among any semiconductor switching devices.
Methyl alcohol poisoning. (Experience of an outbreak in Bombay).

Etude de 47 sujets empoisonnes par du methanol. Les symptomes observes sont variables et apparaissent apres une periode de latence probablement due a une ingestion concomitante d'ethanol. Des modifications oculaires sont les aspects les plus caracteristiques (70,2%). Tous les sujets presentent une acidose. Un hematocrite est eleve chez 35 sujets et une hypokalemie est observee chez 8 sujets. 2 sujets moururent avant qu'un traitement soit instaure
Trends of Postmenopausal Estrogen Plus Progestin Prevalence in the United States Between 1970 and 2010

OBJECTIVE: To estimate long term trends in estrogen–progestin prevalence for the U.S. female population by year and age. METHODS: We integrated data on oral estrogen–progestin use from the National Health and Nutrition Examination Survey 1999–2010 with data from the National Prescription Audit 1970–2003. Distributions of estrogen–progestin by age from the National Health and Nutrition Examination Survey were applied to the prescription data, and calibration and interpolation procedures were used to generate estrogen–progestin prevalence estimates by single year of age and single calendar year for 1970–2010. RESULTS: Estimated prevalence of oral estrogen–progestin was below 0.5% in the 1970s, began to rise in the early 1980s, and almost tripled between 1990 and the late 1990s. The age-adjusted prevalence for women aged 45–64 years peaked at 13.5% in 1999 with highest use among 57-year-old women (23.2%). Prevalence of estrogen–progestin use declined dramatically in the early 2000s with only 2.7% of women aged 45–64 years using estrogen–progestin in 2010, which is comparable to prevalence levels in the mid-1980s. CONCLUSION: The dramatic rise and fall of estrogen–progestin use over the past 40 years provides an illuminating case study of prescription practices before, during, and after the development of evidence regarding benefits and harms. LEVEL OF EVIDENCE: II