Miracle-dz/UniFAR-FTUs huggingface dataset:
Studies on the Mode of Vasodilating Action of Carvedilol*

Summary: Investigations were performed on isolated rat aortic strips and in pithed rats in order to elucidate the mechanism of vasorelaxation or the acute blood pressure lowering effect induced by carvedilol. In particular, the possible role of the &bgr;‐receptor‐stimulating activities or &agr;‐blocking properties has been investigated. &bgr;2‐stimulation can be ruled out, since preincubation of isolated vessels with the &bgr;2‐receptor blocker ICI 118.551 does not influence the vasorelaxing activity of carvedilol. Additionally, its optical enantiomers also induce the same vasorelaxing effect in vitro. In contrast to the standard &agr;‐blocking agents phentolamine or prazosin, carvedilol does not inhibit effects of &agr;‐receptor agonists at hypotensive doses, but inhibition of the effects of &agr;‐receptor agonists has been found in vitro and in vivo at high concentrations or doses and indicates a potential &agr;‐blocking activity of carvedilol. For example, the dose required for a specific inhibitory effect on norepinephrine responses observed in pithed rats is at least 20 times higher than that required for a decrease in blood pressure in spontaneously hypertensive rats. Furthermore, the &agr;‐blocking activity is at least 20 times lower than the &bgr;‐blocking activity, whereas hypotension and &bgr;‐blockade can be observed in intact animals after acute administration in the same dose range of carvedilol. It can therefore be assumed that the &agr;‐blocking activity does not contribute substantially to the decrease in blood pressure at doses normally used. It is suggested that a not yet defined postreceptor mechanism is involved in the vasorelaxing and acute blood pressure lowering activity of carvedilol.
Permanent Growth Arrest in Irradiated Human Fibroblasts

Abstract Savell, J., Rao, S. , Pledger, W. J. and Wharton, W. Permanent Growth Arrest in Irradiated Human Fibroblasts. Exposure of human fibroblasts to doses of ionizing radiation sufficient to cause a permanent growth arrest repressed the expression of genes induced late during G0/G1-phase traverse, including both cyclin A and cyclin E. In addition, radiation prevented the cell cycle-dependent activation of cyclin D1-associated kinase activity and the subsequent phosphorylation of the RB tumor suppressor protein. Exposure to radiation did not alter the cellular levels of cyclin D1 protein, nor did it alter the formation of cyclin D1-CDK4 complexes. Surprisingly, the repression of cyclin D1-associated kinase activity in damaged mitogen-stimulated quiescent cells could not be accounted for by a relative increase in the association of CDKN1A (also known as p21Cip1) with cyclin D1 complexes, nor was cyclin D1 activity targeted by increased levels of CDKN1A in irradiated, logarithmically growing cultures under conditions where cyclin A activity was acutely repressed. Therefore, a radiation-induced permanent growth arrest is mediated by pathways that are distinct from those that cause cell cycle delay in damaged cells involving repression of cyclin-dependent kinase activity by CDKN1A.
Expression of basic and acidic fibroblast growth factors and their receptor in normal and atherosclerotic human arteries.

OBJECTIVE Acidic and basic fibroblast growth factors (FGF) are potent mitogens for vascular endothelial and smooth muscle cells and also promote angiogenesis. Given that atheroma is associated with the proliferation of a range of cell types, including smooth muscle cells, it has been proposed that these growth factors may play a part in the genesis and/or maintenance of atheromatous lesions. The aim of our study was to examine the distribution of acidic and basic FGF and their known receptor, fibroblast growth factor receptor 1 (FGFR-1), in normal and atherosclerotic arteries. METHODS Formalin fixed was embedded archival material from a wide range of vessels was examined using a three stage avidin-biotin immunoperoxidase technique and specific polyclonal antibodies to acidic and basic FGF and FGFR-1. RESULTS In normal arteries basic FGF immunoreactivity was found in medial smooth muscle cells and adventitial blood vessels, the luminal endothelium being non-reactive. Acidic FGF expression was observed predominantly in adventitial fibroblasts, while FGFR-1 expression was confined to the adventitial microvasculature. In early, simple, and advanced lesions acidic and basic FGF were expressed in macrophages and smooth muscle cells, the principal cell types involved in atherosclerotic lesion formation. Increased expression of basic FGF and FGFR-1 was particularly associated with neovascularisation of the atheromatous lesions. CONCLUSIONS Acidic and basic FGF are expressed in early, simple and advanced atherosclerotic plaques. This suggests that in vivo these growth factors may have a role in the genesis of this disease. Basic FGF and FGFR-1 may potentially be involved in plaque neovascularisation. Such FGF driven angiogenic events may be central to the life threatening complications of atheroma and provide new options for therapeutic intervention.
Resveratrol-loaded nanoparticles conjugated with kidney injury molecule-1 as a drug delivery system for potential use in chronic kidney disease.

AIM We used resveratrol (Res)-loaded nanoparticles (Res NPs) as a novel method for improving the pharmacokinetic properties of Res and analyzed the effect of Res NPs in chronic kidney disease (CKD). MATERIALS & METHODS We coupled anti-kidney injury molecule-1 antibodies to Res NPs and analyzed safety and efficacy. RESULTS Res NPs had low toxicity and induced autophagy. Res NPs inhibited the NLRP3 inflammasome and IL-1β secretion. Higher NLRP3 expression levels were observed in peripheral blood monocytic cells of CKD patients than healthy individuals. Treatment with kidney injury molecule-1-Res NPs significantly reduced creatinine and protected against tubulointerstitial injury in a murine model of CKD. CONCLUSION Res NPs through NLRP3 inflammasome attenuation and autophagy induction may be as a strategy to prevent CKD.
Mitotic DNA damage response: Polo-like Kinase-1 is dephosphorylated through ATM-Chk1 pathway

DNA damage during the cell division cycle can activate ATM/ATR and their downstream kinases that are involved in the checkpoint pathway, and cell growth is halted until damage is repaired. As a result of DNA damage induced in mitotic cells by doxorubicin treatment, cells accumulate in a G2-like phase, not in mitosis. Under these conditions, two mitosis-specific kinases, Cdk1 and Plk1, are inhibited by inhibitory phosphorylation and dephosphorylation, respectively. G2-specific phosphorylation of Cdc25 was increased during incubation after mitotic DNA damage. Inhibition of Plk1 through dephosphorylation was dependent on ATM/Chk1 activity. Depleted expression of ATM and Chk1 was achieved using small hairpin RNA (shRNA) plasmid constructs. In this condition, damaged mitotic cells did not accumulated in a G2-like stage, and entered into G1 phase without delay. Protein phosphatase 2A was responsible for dephosphorylation of mitotic Plk1 in response to DNA damage. In knockdown of PP2A catalytic subunits, Plk1 was not dephosphorylated, but rather degraded in response to DNA damage, and cells did not accumulate in G2-like phase. The effect of ATM/Chk1 inhibition was counteracted by overexpression of PP2A, indicated that PP2A may function as a downstream target of ATM/Chk1 at a mitotic DNA damage checkpoint, or may have a dominant effect on ATM/Chk1 function at this checkpoint. Finally, we have shown that negative regulation of Plk1 by dephosphorylation is important to cell accumulation in G2-like phase at the mitotic DNA damage checkpoint, and that this ATM/Chk1/PP2A pathway independent on p53 is a novel mechanism of cellular response to mitotic DNA damage.
Attribute-Oriented Induction in Relational Databases

It is beneficial as well as challenging to learn knowledge rules from relational databases because of the vast amount of knowledge implied in databases and the large amount of data stored in databases. In this thesis, we develop an attributeoriented induction method to extract characteristic rules and classification rules from relational databases. The method adopts the artificial intelligence "learning from examples" paradigm and applies an attribute-oriented concept tree ascending technique in the learning process which integrates database operations with the learning process and provides a simple, efficient way of learning from large databases. Conjunctive rules as well as restricted forms of disjunctive rules are learned using this method. Moreover, by incorporating statistical techniques, qualitative rules with quantitative information can be learned and noisy data and exceptional cases are elegantly handled. Our analysis of the algorithms indicates that attribute-oriented induction substantially reduces the complexity of database learning processes. A prototype database learning system, DBLEARN, has been designed and implemented; early experiments with the prototype system illustrate the promise of attribute-oriented learning in relational databases.
A prospective study of the onset of PTSD symptoms in the first month after trauma exposure.

BACKGROUND The course of posttraumatic stress disorder (PTSD) symptoms in the month after trauma exposure has not been determined adequately. Symptom group C (avoidance/numbing) has been identified retrospectively as a marker for PTSD, but prospective studies are needed to determine whether these symptoms can provide substantially earlier identification of those who will have PTSD 1 month after trauma exposure. METHODS We evaluated 42 patients hospitalized for traumatic injuries over the first post-injury month to track development of posttraumatic symptoms. RESULTS Symptoms emerged rapidly, with group B (intrusion) and group D (hyperarousal) symptoms occurring earlier than group C symptoms. At 1 week, group C criteria accurately predicted who would develop PTSD by 1 month, and by 2 weeks, group C criteria also predicted who would not develop PTSD by 1 month. CONCLUSIONS The findings, if replicated, may permit earlier identification of PTSD and more timely, appropriate treatment.
Interprocedural Parallelization Analysis: A Case Study

We present an overview of our interprocedural analysis system, which applies the program analysis required for parallelization across procedure boundaries. We discuss the issues we addressed to efficiently obtain precise results in the interprocedural setting. We present the analysis required for parallelization, illustrated with an excerpt from a Fortran benchmark program. By integrating a comprehensive suite of interprocedural analyses, we have built a system that is much more effective at locating parallelism in scientific benchmarks than earlier interprocedural systems.
Decentralized Adaptive and Nonadaptive Position/Force Controllers for Redundant Manipulators in Cooperations

This paper addresses the problem of controlling positions and forces of multiple redundant manipulators cooperatively handling an ob ject in a decentralized manner while optimizing a performance in dex. The authors propose one adaptive and two nonadaptive de centralized controllers. The adaptive controller is able to cope with unknown or uncertain physical parameters of the system. The Lya punov approach proves that this controller not only yields asymp totic convergence of the position and force errors but also opti mizes the specified performance index. To improve the transition performance, besides the nonadaptive version of the controller, an implicit decentralized force controller with exponential stability is developed. The controllers realize the force and position controls simultaneously by using coupled force and position signals. The coupled signals distinguish these methods from traditional hybrid controllers in which decoupling of the signals is a must. The de centralized architectures of all the controllers must be emphasized. In detail, the joint input for each robot is designed in its own state space; thus, no coordinator exists, and the computation cost is less expensive than that of centralized controllers designed in the state space of the whole system.
THE ANTIGENICITY OF MOUSE TROPHOBLAST

The fetus, or at least the placenta, is a homograft possessing some of the genetic characteristics of the father; however, it survives throughout the course of pregnancy in intimate association with maternal decidua and is perfused by maternal blood. In an early statement of this problem, Medawar’ suggested three possible mechanisms that might explain the survival of the conceptus: (1) some form of anatomical separation of the fetus from the mother; (2) antigenic immaturity of the fetus; (3) immunological inertness of the mother. I t has since been shown that the fetus possesses mature transplantation antigens and that the mother is fully able to reject grafts containing these antigen^. ^-^ These facts give support to the idea that there may be a “barrier zone” between mother and fetus which, to be effective, must function in two important respects. I t must not only prevent the sensitization of the mother by antigens derived from the father5 but i t must also prevent the destruction of the fetus when the mother has been previously immunized against the foreign antigens which it contains.2*6 I t would seem unlikely that such a barrier zone could be of uterine or decidual origin since the implantation sites of ectopic pregnancies are frequently devoid of all decidua.7 For such a barrier to be of fetal origin, however, it must not only prevent effective contact between the mother and the antigens of the embryo, but must also be incapable of sensitizing the mother in its own right. Thus it must not itself display histocompatibility antigens in a way that can be appreciated by the mother. The experiments reported here were designed to assess the antigenic capacity of the trophoblast, which is the portion of the conceptus in most intimate contact with the mother. If an immunological buffer zone between mother and fetus exists it was reasoned that the trophoblast must fulfil this role.
Multi-lead ST-monitoring in the early assessment of patients with suspected or confirmed unstable coronary artery disease

This study evaluated the use of multi-lead ST-monitoring in the early assessment of patients with suspected or confirmed unstable coronary artery disease (UCAD). At continuous 12-lead ECG (c12ECG), the definition of an ischemic episode as a transient ST-deviation iÝ0 for at least 1 minute resulted in a good observer agreement (kappa=0.72) and an acceptable incidence of postural ST-changes.When c12ECG was performed from admission and for 12 hours in 630 patients with suspected UCAD, 16% had ischemic episodes. At 30 days, patients with episodes had a higher risk of cardiac death or myocardial infarction (MI) (10% vs. 1.5%). In a multivariate analysis, troponin TiÝ0. 10¦Ig/l and presence of ischemic episodes were independent predictors of cardiac death or MI. When ST-monitoring and troponin T status were combined, patients could be divided into a low-, intermediate-, and high-risk group with 1%, 4% and 12% risk for cardiac death or MI at 30 days of follow up.As a part of a multicenter trial, including patients with UCAD, 1016 patients underwent ST-monitoring with c12ECG or continuous vectorcardiography (cVCG). Ischemia was detected in 32% and 35%, respectively. When the groups with ischemia were compared, the groups were similar with respect to several clinical variables. Thus, these methods identify the same high-risk population.Of the 629 patients treated non-invasively with extended treatment of low-molecular- weight heparin (LMWH) or placebo, 34% had ischemic episodes. In this group at 3 months, patients administered LMWH had a significantly lower risk of death, MI, or revascularization than patients treated with placebo (35.2% vs. 53.4%). In patients without transient ischemic episodes, the outcome in the LMWH and placebo group was similar.Thus, multi-lead monitoring provides important prognostic information early after admission in this population, and seems to identify patients who benefit most from extended antithrombotic treatment.
In Vitro and In Vivo Fitness of Respiratory Syncytial Virus Monoclonal Antibody Escape Mutants

ABSTRACT Respiratory syncytial virus (RSV) is the only infectious disease for which a monoclonal antibody (MAb) is used in humans. Palivizumab (PZ) is a humanized murine MAb to the F protein of RSV. PZ-resistant viruses appear after in vitro and in vivo growth of RSV in the presence of PZ. Fitness for replication could be a determinant of the likelihood of dissemination of resistant viruses. We assessed the fitness of two PZ-resistant viruses (F212 and MP4). F212 grew less well in cell culture than the parent A2 virus and was predicted to be less fit than A2. Equal amounts of F212 and A2 were mixed and passaged in cell culture. F212 disappeared from the viral population, indicating it was less fit than the A2 virus. The MP4 virus grew as well as A2 in culture and in cotton rats. A2/MP4 virus input ratios of 1:1, 10:1, 100:1, and 1,000:1 were compared in competitive replication. For all input ratios except 1,000:1, the MP4 virus became dominant, supplanting the A2 virus. The MP4 virus also dominated the A2 virus during growth in cotton rats. Thus, the mutant MP4 virus was more fit than A2 virus in both in vitro and in vivo competitive replication. Whether this fitness difference was due to the identified nucleotide substitutions in the F gene or to mutations elsewhere in the genome is unknown. Understanding the mechanisms by which mutant virus fitness increased or decreased could prove useful for consideration in attenuated vaccine design efforts.
Genetic Analysis of a Chromosomal Region Containing Genes Required for Assimilation of Allantoin Nitrogen and Linked Glyoxylate Metabolism in Escherichia coli

ABSTRACT Growth experiments with Escherichia coli have shown that this organism is able to use allantoin as a sole nitrogen source but not as a sole carbon source. Nitrogen assimilation from this compound was possible only under anaerobic conditions, in which all the enzyme activities involved in allantoin metabolism were detected. Of the nine genes encoding proteins required for allantoin degradation, only the one encoding glyoxylate carboligase (gcl), the first enzyme of the pathway leading to glycerate, had been identified and mapped at centisome 12 on the chromosome map. Phenotypic complementation of mutations in the other two genes of the glycerate pathway, encoding tartronic semialdehyde reductase (glxR) and glycerate kinase (glxK), allowed us to clone and map them closely linked to gcl. Complete sequencing of a 15.8-kb fragment encompassing these genes defined a regulon with 12 open reading frames (ORFs). Due to the high similarity of the products of two of these ORFs with yeast allantoinase and yeast allantoate amidohydrolase, a systematic analysis of the gene cluster was undertaken to identify genes involved in allantoin utilization. A BLASTP search predicted four of the genes that we sequenced to encode allantoinase (allB), allantoate amidohydrolase (allC), ureidoglycolate hydrolase (allA), and ureidoglycolate dehydrogenase (allD). The products of these genes were overexpressed and shown to have the predicted corresponding enzyme activities. Transcriptional fusions to lacZpermitted the identification of three functional promoters corresponding to three transcriptional units for the structural genes and another promoter for the regulatory gene allR. Deletion of this regulatory gene led to constitutive expression of the regulon, indicating a negatively acting function.
Effects of Bowman-Birk Inhibitor on Rat Colon Carcinogenesis

The present study was undertaken to determine whether the Bowman-Birk inhibitor (BBI) could prevent colon carcinogenesis in rats treated with dimethylhydrazine (DMH) and whether there were adverse side effects associated with treatment with BBI for cancer prevention. BBI was evaluated in the forms of purified BBI (PBBI) or an extract of soybeans enriched in BBI, termed BBI concentrate (BBIC). The results demonstrate that PBBI and BBIC reduced the incidence and frequency of tumors in DMH-treated rats compared with animals treated with DMH alone. Autoclaved BBIC, in which the protease inhibitor activity of BBI was destroyed, had a weak and statistically insignificant, suppressive effect on DMH-induced colon carcinogenesis in rats, suggesting that the protease inhibitor activity of BBI is likely to be responsible for the anticarcinogenic activity of BBIC. Soy molasses, which contains soy isoflavones, did not have an effect on colon cancer carcinogenesis in DMH-treated rats. Similar to results from previous studies (Nauss et al. JNCI 73, 915-924, 1984), the most aggressive, malignant colon adenocarcinomas developed within or in association with gut-associated lymphoid tissue aggregates. No adverse side effects on the pancreas or animal growth were observed in rats treated with PBBI or BBIC. These results demonstrate that PBBI and BBIC may be used to prevent colon cancer without significant adverse side effects.
Firefighter Health and Fitness Assessment: A Call to Action

Abstract Storer, TW, Dolezal, BA, Abrazado, ML, Smith, DL, Batalin, MA, Tseng, C-H, and Cooper, CB; The PHASER Study Group. Firefighter health and fitness assessment: A call to action. J Strength Cond Res 28(3): 661–671, 2014—Sudden cardiac deaths experienced by firefighters in the line of duty account for the largest proportion of deaths annually. Several fire service standards for fitness and wellness have been recommended but currently only 30% of U.S. fire departments are implementing programs for this purpose. The Department of Homeland Security Science and Technology Directorate has initiated the Physiological Health Assessment System for Emergency Responders (PHASER) program aiming to reduce these line-of-duty deaths through an integration of medical science and sensor technologies. Confirming previous reports, PHASER comprehensive risk assessment has identified lack of physical fitness with propensity for overexertion as a major modifiable risk factor. We sought to determine if current levels of fitness and cardiovascular disease (CVD) risk factors in a contemporary cohort of firefighters were better than those reported over the past 30 years. Fifty-one firefighters from a Southern California department were characterized for physical fitness and CVD risk factors using standard measures. Overall, physical fitness and risk factors were not different from previous reports of firefighter fitness and most subjects did not achieve recommended fitness standards. Considering the lack of widespread implementation of wellness/fitness programs in the U.S. fire service together with our findings that low physical fitness and the presence of CVD risk factors persist, we issue a call to action among health and fitness professionals to assist the fire service in implementing programs for firefighters that improve fitness and reduce CVD risk factors. Fitness professionals should be empowered to work with fire departments lending their expertise to guide programs that achieve these objectives, which may then lead to reduced incidence of sudden cardiac death or stroke.
Enhanced Electrochromism in Gyroid‐Structured Vanadium Pentoxide

Manufacturing V(2)O(5) in a 3D periodic highly interconnected gyroid structure on the 10 nm length scale is shown to lead to a significant electrochromic performance enhancement. The structured devices surpass previous inorganic electrochromic materials in all relevant parameters: the switching speed, coloration contrast, and composite coloration efficiency. In particular, the 85 ms switching speed lies within a factor of two of video rate. Enhanced ion intercalation into the gyroid morphology can be extended to other transition-metal oxides and is therefore promising for lithium ion batteries, supercapacitors, and sensors.