Miracle-dz/UniFAR-FTUs huggingface dataset:
p 38 Kinase Is a Negative Regulator of Angiotensin II Signal Transduction in Vascular Smooth Muscle Cells Effects on Na 1 / H 1 Exchange and ERK 1 / 2

Activation of the Na /H exchanger isoform-1 (NHE-1) by angiotensin II is an early signal transduction event that may regulate vascular smooth muscle cell (VSMC) growth and migration. Many signal transduction events stimulated by angiotensin II are mediated by the mitogen-activated protein (MAP) kinases. To define their roles in angiotensin II–mediated NHE-1 activity, VSMCs were treated with angiotensin II and the activities of p38, c-Jun N-terminal kinase (JNK), and extracellular signal–regulated kinases 1 and 2 (ERK1/2) were measured. Angiotensin II rapidly (peak, 5 minutes) activated p38 and ERK1/2, whereas JNK was activated more slowly (peak, 30 minutes). Because angiotensin II stimulated Na /H exchange within 5 minutes, the effects of p38 and ERK1/2 antagonists on Na/H exchange were studied. The MEK-1 inhibitor PD98059 decreased ERK1/2 activity and Na /H exchange stimulated by angiotensin II. In contrast, the specific p38 antagonist SKF-86002 increased Na /H exchange. Two mechanisms were identified that may mediate the effects of p38 and SKF-86002 on angiotensin II–stimulated Na /H exchange. First, angiotensin II activation of ERK1/2 was increased 1.5to 2.5-fold (depending on assay technique) in the presence of SKF-86002, demonstrating that p38 negatively regulates ERK1/2. Second, the ability of angiotensin II–stimulated MAP kinases to phosphorylate a glutathione S-transferase fusion protein containing amino acids 625 to 747 of NHE-1 in vitro was analyzed. The relative activities of endogenous immunoprecipitated p38, ERK1/2, and JNK were 1.0, 2.0, and 0.05 versus control, respectively suggesting that p38 and ERK1/2, but not JNK, may phosphorylate NHE-1 in VSMC. These data indicate important roles for p38 and ERK1/2 in angiotensin II–mediated regulation of the Na/H exchanger in VSMC. (Circ Res. 1998;83:824-831.)
Cryopreserved Agarose-Encapsulated Islets As Bioartificial Pancreas: A Feasibility Study

Background. A bioartificial pancreas in which islets of Langerhans (islets) are encapsulated within a semipermeable membrane, such as agarose, has been proposed for treating type I diabetic mellitus. However, the long-term storage for providing a convenient and easily accessible supply still remains an issue. We investigated cryopreservation as a potential method of long-term storage for agarose-encapsulated islets (Mic-islets). Methods. The morphology, insulin secretion, and histochemical staining of cryopreserved Mic-islets were analyzed. Streptozotocin-induced diabetic mice were transplanted intraperitoneally with 1000, 2000, and 3000 Mic-islets after cryopreservation in KYO-1 vitrification solution. Blood glucose levels were measured and immunohistochemical analyses were performed at 41 days posttransplantation. Results. Transplanted cryopreserved Mic-islets restored normoglycemia in diabetic mice. The mean (±SD) normoglycemic periods were 32.0±13.2 days and 46.3±13.3 days for recipients of 1000 (n=5) and 2000 (n=4) cryopreserved Mic-islets, respectively, whereas the mean normoglycemic period was 53.2±16.7 days for recipients of 1000 noncryopreserved Mic-islets (n=7). These data indicate that cryopreserved Mic-islets transplanted as a bioartificial pancreas successfully controlled blood glucose levels for extended periods. Conclusion. Cryopreserved agarose-encapsulated islets could successfully control the blood glucose level for a long period as a bioartificial pancreas.
Relaxant effect of Crocus sativus (saffron) on guinea‐pig tracheal chains and its possible mechanisms

As indicated in ancient Iranian medical books, Crocus sativus has therapeutic effects on respiratory diseases. The relaxant effect of this plant has been observed also on smooth muscles in previous studies. Therefore, in this study the relaxant effects of aqueous‐ethanolic extracts of C. sativus and one of its main constituents, safranal, were examined on guinea‐pig tracheal chains. The relaxant effects of four cumulative concentrations of aqueous‐ethanolic extract (0.15, 0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL−1 solution) in comparison with saline, as negative control, and four cumulative concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive control, were examined using guinea‐pig precontracted tracheal chains. The tracheal chains had been precontracted by three different methods. Group 1 had been precontracted using 10 μM methacholine. The other two groups had been precontracted using 60 mM KCl at two different conditions: non‐incubated tissues (group 2) and tissues incubated with 1 μM propranolol, 1 μM chlorpheniramine and 1 μM atropine (group 3) (for each group, n = 6). In group 1 all concentrations of theophylline, extract and safranal showed significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In group 2 theophylline, extract and safranal showed concentration‐dependent relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different concentrations except two low concentrations of safranal). However, in group 3 the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the highest concentration). The effects of the last concentration of safranal (0.60 mL 0.2 mg mL−1 solution) in group 1, and all its concentrations in group 2 were significantly lower than those of theophylline (P < 0.05 to P < 0.001). In addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL−1 solution in groups 1 and 2 were significantly lower than that of C. sativus extract. There were significant correlations between the relaxant effects and concentrations for extract, safranal and theophylline in all experimental groups (P < 0.001 for all cases). These results showed a potent relaxant effect of C. sativus on tracheal chains of guinea‐pigs that was comparable to or even higher than that of theophylline at the concentrations used. The results indicated that safranal was, at least in part, responsible for the relaxant effect of C. sativus.
Objective performance evaluation on mountain routes of diesel-electric hybrid busses

The application of hybrid buses for public transport on mountain route is an attractive idea because of the low pollutant emission footprint in touristic areas and the possibility to exploit the down hill route and the frequent stops to recover energy. Nevertheless the use of these vehicles is challenging for many aspects: technologically, the winter weather conditions may have a detrimental effect on batteries and electrical components, and road profile elevation may not allow to satisfy the target speeds required by the traditional bus' stop-to-stop schedule. In order to objectively assess the possibility to employ such type of vehicles on mountain routes, the actual fuel consumption and emission, logged in field operational tests, are compared with reference optimal stop-to-stop manoeuvres calculated a posteriori, which also include the interaction with the front traffic situation. The optimal reference manoeuvres are calculated based on two multi-physics dynamic models of the series hybrid diesel-electric buses, one with lithium batteries and the second with ultra-capacitors. Here the details of the two model developed are presented and discussed together with the first stage of the validation process carried out with the experimental data collected on-board.
Antigen Selection for Enhanced Affinity T-Cell Receptor–Based Cancer Therapies

Evidence of adaptive immune responses in the prevention of cancer has been accumulating for decades. Spontaneous T-cell responses occur in multiple indications, bringing the study of de novo expressed cancer antigens to the fore and highlighting their potential as targets for cancer immunotherapy. Circumventing the immune-suppressive mechanisms that maintain tumor tolerance and driving an antitumor cytotoxic T-cell response in cancer patients may eradicate the tumor or block disease progression. Multiple strategies are being pursued to harness the cytotoxic potential of T cells clinically. Highly promising results are now emerging. The focus of this review is the target discovery process for cancer immune therapeutics based on affinity-matured T-cell receptors (TCRs). Target cancer antigens in the context of adoptive cell transfer technologies and soluble biologic agents are discussed. To appreciate the impact of TCR-based technology and understand the TCR discovery process, it is necessary to understand key differences between TCR-based therapy and other immunotherapy approaches. The review first summarizes key advances in the cancer immunotherapy field and then discusses the opportunities that TCR technology provides. The nature and breadth of molecular targets that are tractable to this approach are discussed, together with the challenges associated with finding them.
Quality of Life in Patients with Breast Cancer–Related Lymphedema and Reconstructive Breast Surgery

Abstract Background To evaluate the quality of life (QOL) of breast cancer survivors who have undergone breast reconstruction and have breast cancer–related lymphedema (BCRL). Methods Patients with a unilateral mastectomy with or without breast reconstruction were evaluated for BCRL and their QOL. Patients were divided into a non-BCRL and a BCRL group. Patients with subjective complaints of arm swelling and/or an interlimb volume difference of >200 mL, or undergoing treatment for arm lymphedema were defined as having BCRL. QOL was assessed using cancer-specific (EORTC QLQ-C30 and EORTC QLQ-B23) and disease specific (Lymph-ICF) questionnaires. Results In total, 253 patients with a mean follow-up time of 51.7 (standard deviation = 18.5) months since mastectomy completed the QOL questionnaires. Of these patients, 116 (46%) underwent mastectomy alone and 137 (54%) had additional breast reconstruction. A comparison of the QOL scores of 180 patients in the non-BCRL group showed a significantly better physical function (p = 0.004) for patients with reconstructive surgery compared with mastectomy patients. In the 73 patients with BCRL, a comparison of the QOL scores showed no significant differences between patients with mastectomy and reconstructive surgery. After adjusting for potential confounders, multivariate analysis showed a significant impact of BCRL on physical function (β = − 7.46; p = 0.009), role function (β = − 15.75; p = 0.003), cognitive function (β = − 11.56; p = 0.005), body vision (β = − 11.62; p = 0.007), arm symptoms (β = 20.78; p = 0.000), and all domains of the Lymph-ICF questionnaire. Conclusions This study implies that BCRL has a negative effect on the QOL of breast cancer survivors, potentially negating the positive effects on QOL reconstructive breast surgery has.
Polymeric Waveguide Film With Embedded Mirror for Multilayer Optical Circuits

A polymeric waveguide film with embedded mirrors is presented for a multilayer optical circuit. For the polymeric waveguide fabrication, arrayed waveguide patterns were directly formed on a metallic master body using ultra-precision machining (UPM) method, and 45deg-angled mirrors as beam reflector were constructed at the master pattern ends. We have achieved excellent surface roughness of the pattern and mirror facet using UPM. The waveguide lines and 45deg-angled mirrors were simultaneously fabricated on an under-clad sheet using an imprint method with a mirror-integrated master. We manufactured polymer waveguide films with embedded beam reflectors and consequently measured the optical characteristics of waveguides.
Cytokine secretion by C3H-lpr and -gld T cells. Hypersecretion of IFN-gamma and tumor necrosis factor-alpha by stimulated CD4+ T cells.

Mice homozygous for lpr and gld develop profound lymphadenopathy characterized by the expansion of two unusual T cell subsets, a predominant Ly-5(B220)+ CD4- CD8- double negative (DN) population and a minor CD4 dull+ Ly-5(B220)+ population. The mechanisms promoting lymphoproliferation are unknown, but one possibility is a abnormality in the production of cytokines that regulate T cell growth. In the present report, unfractionated LN cells and sorted T cell subsets from C3H-lpr, -gld, and -+/+ mice were compared for spontaneous and induced secretion of a spectrum of lymphokines. In addition, CD4+, CD4 dull+ Ly-5(B220)+, and DN T cells were examined for expression of CD3 epsilon, TCR-alpha/beta heterodimers, Ly-6C, and CD44 and for proliferative responses to immobilized anti-TCR mAb and cofactors. These studies revealed that sorted DN T cells did not secrete IL-3, IL-4, IL-5, IL-6, GM-CSF, TNF-alpha, or IFN-gamma spontaneously or after TCR-alpha/beta cross-linking. In contrast, stimulated unfractionated lpr and gld LN cells proliferated strongly and secreted high levels of IFN-gamma and TNF-alpha and low levels of IL-3, IL-4, and IL-6. Despite a 5- to 10-fold deficit in the frequency of CD4+ and CD8+ T cells, cytokine secretion by lpr and gld LN generally exceeded that of +/+ LN. Comparisons of cytokine secretion by stimulated CD4+ T cells revealed that +/+, lpr, and gld CD4+ Ly-5(B220)- T cells proliferated strongly, but only lpr and gld cells produced significant levels of IFN-gamma. The lpr and gld CD4+ T cells also produced higher levels of TNF-alpha and IL-2 than +/+ cells. In contrast to normal CD4+ T cells, lpr and gld CD4+ Ly-5(B220)+ T cells proliferated weakly and did not secrete TNF-alpha, IL-2, or, in most experiments, IFN-gamma after stimulation. Phenotypic studies of T cell subsets revealed that unstimulated lpr and gld CD4+ Ly-5(B220)- T cells express significantly higher levels of CD44 than +/+ CD4+ T cells. In addition, CD4 dull+ Ly-5(B220)+ cells closely resembled DN T cells in size and expression of TCR-alpha/beta, CD3epsilon, CD44, and Ly-6C. Since elevated CD44 expression is generally associated with T cell activation and only previously activated normal CD4+ T cells produce high levels of IFN-gamma in vitro, our data suggest that lpr and gld CD4+ Ly-5(B220)- T cells contain a higher than normal proportion of primed or memory T cells and thus may be polyclonally activated in vivo. (ABSTRACT TRUNCATED AT 400 WORDS)
B-Cell Deficiency Predisposes Mice to Disseminating Anaerobic Infections: Protection by Passive Antibody Transfer

ABSTRACT We have previously demonstrated that a high proportion of RAG-2 SCID knockout mice, which lack T and B cells, develop orofacial abscesses and disseminated infections following pulpal infection, whereas immunocompetent control mice do not. In the present study, we sought to identify the components of the adaptive immune response which contribute to protection against disseminating anaerobic infections and sepsis. For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc0 (C5 deficient). For abscess induction, the mandibular first molars were subjected to pulp exposure on day 0. Teeth were infected with a mixture of four anaerobic pathogens, including Prevotella intermedia, Streptococcus intermedius,Fusobacterium nucleatum, and Peptostreptococcus micros, and teeth were sealed to prevent communication with the oral cavity. The findings demonstrate that both RAG-2 SCID and B-cell-deficient mice, but not T-cell- or C5-deficient mice, have increased susceptibility to the development of disseminating anaerobic infections. Abscess-susceptible RAG-2 SCID and B-cell-deficient mice also showed a significant loss of body weight, splenomegaly, and absent antibacterial antibody production. Furthermore, dissemination was significantly reduced, from 74 to 25%, in susceptible RAG-2 mice by passively transferred antibody, predominantly immunoglobulin G2b (IgG2b) and IgM, against the infecting bacterial innoculum. Fractionated IgG-enriched preparations were more efficient in transferring protection than IgM preparations. We conclude that an antibody-mediated mechanism(s), most likely bacterial opsonization, is of importance in localizing anaerobic root canal infections and in preventing their systemic spread.
Methacholine and ovalbumin challenges assessed by forced oscillations and synchrotron lung imaging.

RATIONALE Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization. OBJECTIVES To compare (1) the central versus peripheral effects of Mch and Ova within the lung by combining measurements of airway and tissue mechanics with synchrotron radiation (SR) imaging, and (2) to assess the extent to which mechanical and imaging parameters are correlated. METHODS We used the low-frequency forced oscillation technique and SR imaging in control (n = 12) and ovalbumin-sensitized (n = 13) rabbits, at baseline, during intravenous Mch infusion (2.5 microg/kg/min, 5.0 microg/kg/min, or 10.0 microg/kg/min), after recovery from Mch, and after intravenous Ova injection (2.0 mg). We compared intravenous Mch challenge with inhaled Mch (125 mg/ml, 90 s) in a separate group of control animals (n = 5). MEASUREMENTS AND MAIN RESULTS Airway conductance and tissue elastance were measured by low-frequency forced oscillation technique. The central airway cross-sectional area, the ventilated alveolar area, and the heterogeneity of specific ventilation were quantified by SR imaging. Mch infusion induced constriction predominantly in the central airways, whereas Ova provocation affected mainly the peripheral airways, leading to severe ventilation heterogeneities in sensitized animals. Mch inhalation affected both conducting and peripheral airways. The correlations between airway conductance and central airway cross-sectional area (R = 0.71) and between tissue elastance and ventilated alveolar area (R = -0.72) were strong. CONCLUSIONS The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.
Glycogen synthase kinase 3: a drug target for CNS therapies

Glycogen synthase kinase3 (GSK3) is emerging as a prominent drug target in the CNS. The most exciting of the possibilities of GSK3 lies within the treatment of Alzheimer's disease (AD) where abnormal increases in GSK3 levels and activity have been associated with neuronal death, paired helical filament tau formation and neurite retraction as well as a decline in cognitive performance. Abnormal activity of GSK3 is also implicated in stroke. Lithium, a widely used drug for affective disorders, inhibits GSK3 at therapeutically relevant concentrations. Thus while the rationale remains testable, pharmaceutical companies are investing in finding a selective inhibitor of GSK3. In the present review, we summarize the properties of GSK3, and discuss the potential for such a therapy in AD, and other CNS disorders.
Bone metabolism markers and ghrelin in boys at different stages of sexual maturity

Aim: To examine the relationship of the markers of bone formation (procollagen type I N‐terminal propeptide [PINP]) and bone resorption (type I carboxyterminal telopeptide [ICTP]) with bone mineral content (BMC), bone mineral density (BMD), ghrelin and testosterone in boys during puberty.
Interrelationships among Atg proteins during autophagy in Saccharomyces cerevisiae

Macroautophagy is a bulk degradation process induced by nutrient starvation in eukaryotic cells. In Saccharomyces cerevisiae, 16 ATG genes are essential for autophagosome formation. Recently, we demonstrated that these ATG genes can be classified into three groups on the basis of localization of GFP–Atg8p/Aut7p and Atg5p/Apg5p–GFP under nutrient‐rich conditions. In this study, we analysed the intracellular localization of GFP–Atg8p, an autophagosome marker, in atg mutants under autophagy‐inducing conditions; the localization of GFP–Atg8p exhibited several distinct patterns. Subsequent analyses revealed epistatic interrelationships among Atg proteins during the process of autophagosome formation. Copyright © 2004 John Wiley & Sons, Ltd.
An autoregressive approach to spatio‐temporal disease mapping

Disease mapping has been a very active research field during recent years. Nevertheless, time trends in risks have been ignored in most of these studies, yet they can provide information with a very high epidemiological value. Lately, several spatio‐temporal models have been proposed, either based on a parametric description of time trends, on independent risk estimates for every period, or on the definition of the joint covariance matrix for all the periods as a Kronecker product of matrices. The following paper offers an autoregressive approach to spatio‐temporal disease mapping by fusing ideas from autoregressive time series in order to link information in time and by spatial modelling to link information in space. Our proposal can be easily implemented in Bayesian simulation software packages, for example WinBUGS. As a result, risk estimates are obtained for every region related to those in their neighbours and to those in the same region in adjacent periods. Copyright © 2007 John Wiley & Sons, Ltd.
Context Modeling Approach for Geospatial Information Service

The main idea of pervasive computing is to embed computer into the living environment or tool of human, so as to make the computer invisible from userpsilas sight and the users can focus on their task itself, instead of the computer. As having natural relationship with the spatial distribution and mobile, the pervasive computing has been applied in geospatial information areas widely. However, the pervasive computing has brought challenges to the geospatial information science, and the first step of the solution to this challenge should be the modeling of geospatial context . This paper summarizes and analyses typical geospatial context, builds up a formal context model for geospatial information service based on ontology. The model is designed hierarchically and the context is expressed using the Web ontology language (OWL), which improves context expressing ability. Finally, this paper designs a context-aware computing model for geospatial information.
A [‐2]proPSA‐based artificial neural network significantly improves differentiation between prostate cancer and benign prostatic diseases

The aim of this study was to combine the new automated Access [‐2]proPSA (p2PSA) assay with a percent free PSA (%fPSA) based artificial neural network (ANN) or logistic regression (LR) model to enhance discrimination between patients with prostate cancer (PCa) and with no evidence of malignancy (NEM) and to detect aggressive PCa.