Hierarchy and inhomogeneity in the systematic structure of the mammalian myocardium: Towards a comprehensive view of cardiodynamics

2012 ◽  
Vol 20 (5) ◽  
pp. 423-434 ◽  
Author(s):  
Paul Peter Lunkenheimer ◽  
Peter Niederer
Keyword(s):  
Comprehensive View ◽  
Mammalian Myocardium ◽  
Systematic Structure

Analysis of Functioning the School Council at Primary School

2012 ◽  
Vol 2 (3) ◽  
pp. 7-31
Author(s):  
Jitka Vidláková
Keyword(s):  
Primary School ◽  
Stages Of Change ◽  
School Council ◽  
School Life ◽  
School Practice ◽  
Comprehensive View ◽  
Student Council

The topic of the contribution is pupil participation in school life. In this framework we will focus on student councils, which represent one of the possible forms of pupil participation. The study analyzes the foundation and the existence of a student council at a selected primary school using a modified Lagerwei’s model of stages of change. In the text we present a comprehensive view on the functioning of student council, as we confront the data relating to its activities obtained from the headmaster, teachers and pupils. The study focuses primarily on researchers dealing with the issue of pupil participation but its focus also brings ideas and inspiration for other professionals and for school practice.

Comprehensive View on Recent Developments in Hydrogen Evolution Using MoS2 on Si Photocathode: from Electronic to Electrochemical Aspects

2021 ◽  
Author(s):  
Anirudha Jena ◽  
Chih-Jung Chen ◽  
Ho Chang ◽  
Shu-Fen Hu ◽  
Ru-Shi Liu
Keyword(s):  
Hydrogen Evolution ◽  
Water Electrolysis ◽  
Clean Energy ◽  
Alternative Route ◽  
Comprehensive View ◽  
Recent Developments ◽  
Technological Developments

The generation of clean energy is necessary for future technological developments. The utilization of solar illumination to produce H2 from water electrolysis is an alternative route to address the issue....

scholarly journals Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1380
Author(s):  
Xiutao Wu ◽  
Lijie Gong ◽  
Chen Chen ◽  
Ye Tao ◽  
Wuxi Zhou ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Normal Cell ◽  
Selectivity Index ◽  
Cytotoxic Activities ◽  
Structure Activity ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Hct 116 ◽  
Systematic Structure

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.

scholarly journals Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suxing Liu ◽  
Dong Liu ◽  
Ru Shen ◽  
Di Li ◽  
Qiyue Hu ◽  
...  
Keyword(s):  
Topical Treatment ◽  
Clinical Success ◽  
Systemic Exposure ◽  
Skin Inflammation ◽  
Targeted Therapeutics ◽  
High Exposure ◽  
Structure Activity ◽  
Potential Safety ◽  
Systematic Structure ◽  
And Function

AbstractClinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development. To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use is of great interest. Systematic structure activity relationship study and multi-parameter optimization led to the discovery of a novel RORγ antagonist (SHR168442) with desired properties for a topical drug. It suppressed the transcription of IL-17 gene, leading to reduction of IL-17 cytokine secretion. It showed high exposure in skin, but low in plasma. Topical application of SHR168442 in Vaseline exhibited excellent efficacy in the imiquimod-induced and IL-23-induced psoriasis-like skin inflammation mouse models and correlated with the reduction of Th17 pathway cytokines, IL-6, TNFα and IL-17A. This work demonstrated restricted skin exposure of RORγ antagonist may provide a new topical treatment option as targeted therapeutics for mild to moderate psoriasis patients and may be suitable for the treatment of any other inflammatory disorders that are accessible locally.

A comprehensive view of the arguments for doing space

Space Policy ◽  
1993 ◽  
Vol 9 (4) ◽  
pp. 345-347
Author(s):  
Philip R. Harris
Keyword(s):  
Comprehensive View

scholarly journals Effects of acidosis on resting cytosolic and mitochondrial Ca2+ in mammalian myocardium.

1993 ◽  
Vol 102 (3) ◽  
pp. 575-597 ◽  
Author(s):  
G Gambassi ◽  
R G Hansford ◽  
S J Sollott ◽  
B A Hogue ◽  
E G Lakatta ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Ventricular Myocytes ◽  
Free Acid ◽  
Left Ventricular ◽  
Ruthenium Red ◽  
Acetoxymethyl Ester ◽  
Cytosolic Ph ◽  
Bicarbonate Buffer ◽  
Adult Rat ◽  
Mammalian Myocardium

Acidosis increases resting cytosolic [Ca2+], (Cai) of myocardial preparations; however, neither the Ca2+ sources for the increase in Cai nor the effect of acidosis on mitochondrial free [Ca2+], (Cam) have been characterized. In this study cytosolic pH (pHi) was monitored in adult rat left ventricular myocytes loaded with the acetoxymethyl ester (AM form) of SNARF-1. A stable decrease in the pHi of 0.52 +/- 0.05 U (n = 16) was obtained by switching from a bicarbonate buffer equilibrated with 5% CO2 to a buffer equilibrated with 20% CO2. Electrical stimulation at either 0.5 or 1.5 Hz had no effect on pHi in 5% CO2, nor did it affect the magnitude of pHi decrease in response to hypercarbic acidosis. Cai was measured in myocytes loaded with indo-1/free acid and Cam was monitored in cells loaded with indo-1/AM after quenching cytosolic indo-1 fluorescence with MnCl2. In quiescent intact myocytes bathed in 1.5 mM [Ca2+], hypercarbia increased Cai from 130 +/- 5 to 221 +/- 13 nM. However, when acidosis was effected in electrically stimulated myocytes, diastolic Cai increased more than resting Cai in quiescent myocytes, and during pacing at 1.5 Hz diastolic Cai was higher (285 +/- 17 nM) than at 0.5 Hz (245 +/- 18 nM; P < 0.05). The magnitude of Cai increase in quiescent myocytes was not affected either by sarcoplasmic reticulum (SR) Ca2+ depletion with ryanodine or by SR Ca2+ depletion and concomitant superfusion with a Ca(2+)-free buffer. In unstimulated intact myocytes hypercarbia increased Cam from 95 +/- 12 to 147 +/- 19 nM and this response was not modified either by ryanodine and a Ca(2+)-free buffer or by 50 microM ruthenium red in order to block the mitochondrial uniporter. In mitochondrial suspensions loaded either with BCECF/AM or indo-1/AM, acidosis produced by lactic acid addition decreased both intra- and extramitochondrial pH and increased Cam. Studies of mitochondrial suspensions bathed in indo-1/free acid-containing solution showed an increase in extramitochondrial Ca2+ after the addition of lactic acid. Thus, in quiescent myocytes, cytoplasmic and intramitochondrial buffers, rather than transsarcolemmal Ca2+ influx or SR Ca2+ release, are the likely Ca2+ sources for the increase in Cai and Cam, respectively; additionally, Ca2+ efflux from the mitochondria may contribute to the raise in Cai. In contrast, in response to acidosis, diastolic Cai in electrically stimulated myocytes increases more than resting Cai in quiescent cells; this suggests that during pacing, net cell Ca2+ gain contributes to enhance diastolic Cai.

scholarly journals A Few Issues Surrounding Research into the General History of Chinese Film

2021 ◽  
Vol 1 (1) ◽  
pp. 83-99
Author(s):  
Yaping Ding
Keyword(s):  
Film History ◽  
Scientific Discipline ◽  
History Writing ◽  
Chinese Film ◽  
Comprehensive View ◽  
Broad Scope ◽  
History Of

Abstract The practice of film history highlights the value and significance of the researcher. A more comprehensive view of the situation of film history raises several issues. General research into the history of film is directly related to the production of film history. The question of how to reinvent general film history research is necessarily connected to ideologies, cultures, systems and concepts, as well as the broad scope and complexity of film history. Writing a general history of Chinese film demands a combination of innovation and continuing tradition, with an emphasis on the construction of a rational and scientific discipline of film history and historical empiricism. The aim should be a more rational history. The paper expresses my own thoughts and efforts with respect to relevant issues and attempts to deepen and open up general research into the history of Chinese film.

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