scholarly journals Fluorescence-Labeled Amyloid Beta Monomer: A Molecular Dynamical Study

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3524
Author(s):  
János Gera ◽  
Gábor Paragi
Keyword(s):  
Single Molecule ◽  
Early Stage ◽  
Conformational Space ◽  
Dynamic Simulations ◽  
Dynamical Study ◽  
Fluorescence Dye ◽  
Aβ Aggregation ◽  
The Difference ◽  
Open Question ◽  
The Impact

The aggregation process of the Amyloidβ (Aβ) peptide is one of the central questions in Alzheimers’s research. Fluorescence-labeled single-molecule detection is a novel technique concerning the early stage investigation of Aβ aggregation, where the labeling dyes are covalently bound to the Aβ monomer. As the influence of the dye on the conformational space of the Aβ monomer can be significant, its effect on the seeding process is an open question. The applied fluorescent molecule continuously switches between an active (ON) and an inactive (OFF) state, where the latter supports an extra rotational restriction at many commercially available dyes. However, only a few theoretical studies simulated the Aβ monomer in the presence of a dye and none of them considered the difference between the ON and the OFF states. Therefore, we examined the impact of a selected fluorescence dye (Alexa 568) on the conformational space of the monomeric Aβ(1–42) peptide in its ON and OFF state by replica exchange molecular dynamic simulations. Investigations on secondary structure elements as well as dye-peptide contact analysis for the monomers are presented. Experimental and theoretical NMR shifts were contrasted to qualify the calculation protocol and theoretical values of the labeled and the non-labeled peptide were also compared. We found that the first five residues have higher helical propensity in the presence of the dye, and electrostatic properties could strongly affect the connection between the dye and the peptide parts.

scholarly journals Requirements for Electric Machine Design based on Operating Points from Real Driving Data in Cities

2019 ◽  
Vol 10 (4) ◽  
pp. 60
Author(s):  
Svenja Kalt ◽  
Lucas Brenner ◽  
Markus Lienkamp
Keyword(s):  
Time Pressure ◽  
Early Stage ◽  
Driving Cycle ◽  
Driving Cycles ◽  
New Concepts ◽  
The Difference ◽  
Electric Machine Design ◽  
The Impact ◽  
Operating Points

Increasing environmental awareness leads to the necessity for more efficient powertrains in the future. However, the development of new vehicle concepts generates a trend towards ever shorter development cycles. Therefore, new concepts must be tested and validated at an early stage in order to meet the increasing time pressure. This requires the determination of real driving data in fleet tests in order to generate realistic driving cycles, which correspond as closely as possible to the actual driving behavior of the applications use case. Within the scope of this paper, real driving data are analyzed and used to create a representative driving cycle. The resulting driving cycle based on real driving characteristics is then used to investigate the impact of application-based design for powertrains on the design of electric machines, by illustrating the difference between synthetic operating points and real driving data.

scholarly journals PIP2 promotes conformation-specific dimerization of the EphA2 membrane region

2020 ◽  
Author(s):  
Katherine M. Stefanski ◽  
Charles M. Russell ◽  
Justin M. Westerfield ◽  
Rajan Lamichhane ◽  
Francisco N. Barrera
Keyword(s):  
Single Molecule ◽  
Oncogenic Signaling ◽  
Independent States ◽  
Conformational Coupling ◽  
The Difference ◽  
Tm Domain ◽  
Hydrophobic Matching ◽  
The Impact ◽  
Membrane Region ◽  
Positively Charged

AbstractThe impact of the EphA2 receptor on cancer malignancy hinges on the two different ways it can be activated. EphA2 induces anti-oncogenic signaling after ligand binding, but ligand-independent activation of EphA2 is pro-oncogenic. It is believed that the transmembrane (TM) domain of EphA2 adopts two alternate conformations in the ligand-dependent and the ligand-independent states. However, it is poorly understood how the difference in TM helical crossing angles found in the two conformations impacts the activity and regulation of EphA2. We devised a method that uses hydrophobic matching to stabilize two conformations of a peptide comprising the EphA2 TM domain and a portion of the intracellular juxtamembrane (JM) segment. The two conformations exhibit different TM crossing angles, resembling the ligand-dependent and ligand-independent states. We developed a single-molecule technique using SMALPs to measure dimerization in membranes. We observed that the signaling lipid PIP2 promotes TM dimerization, but only in the small crossing angle state, which we propose corresponds to the ligand-independent conformation. In this state the two TM are almost parallel, and the positively charged JM segments are expected to be close to each other, causing electrostatic repulsion. The mechanism PIP2 uses to promote dimerization might involve alleviating this repulsion due to its high density of negative charges. Our data reveal a conformational coupling between the TM and JM regions, and suggest that PIP2 might directly exert a regulatory effect on EphA2 activation in cells that is specific to the ligand-independent conformation of the receptor.

scholarly journals Peranan Kadar Feritin Serum terhadap Kejadian Preeklampsia

2015 ◽  
Vol 4 (3) ◽  
Author(s):  
Mega Ulfah ◽  
Masrul Masrul ◽  
Arni Amir
Keyword(s):  
Serum Level ◽  
Early Stage ◽  
Serum Levels ◽  
Total Sample ◽  
Normal Pregnancy ◽  
P Value ◽  
Excess Iron ◽  
The Difference ◽  
The Impact ◽  
Biomedical Laboratory

Abstrak Preeklampsia merupakan penyebab utama kematian maternal dan perinatal diseluruh dunia. Peningkatan kadar serum besi dan feritin memiliki potensi untuk digunakan secara diagnostik untuk memperingatkan preeklampsia tahap awal. Tujuan penelitian ini adalah untuk menentukan peranan kadar serum feritin terhadap kejadianpreeklampsia. Penelitian ini merupakan penelitian analitik observasional dengan desain case-control. Penelitian dilakukan dari Agustus 2013 hingga Juli 2014, bertempat di RS dr. M. Djamil, RS dr. Reksodiwiryo dan Laboratorium Biomedik UNAND Padang.  Jumlah sampel yang diteliti adalah 40 responden dimana sampel terdiri dari 2 kelompok,masing-masing terdiri dari 20 sampel. Pemeriksaan serum feritin dilakukan dengan metode ELISA. Perbedaan rerata kadar feritin serum antara kelompok preeklampsia dan kehamilan normal dianalisa dengan mengunakan independen ttest. Hasil penelitian diperoleh rerata kadar serum feritin pada kelompok preeklampsia dan kehamilan normal adalah50,46+4,37 ng/ml dan 17,64+1,6 ng/ml, dengan nilai p=0,004. Kadar feritin pada kedua kelompok masih dalam batas normal dan tidak ditemukan indikasi adanya kelebihan besi sebagai faktor resiko preeklampsia. Kesimpulan penelitian ini yaitu kadar serum feritin tidak memiliki peranan terhadap kejadian preeklampsia. Kata kunci: preeklampsia, hipertensi dalam kehamilan, serum feritin Abstract Preeclampsia is a major cause of worldwide maternal and prenatal mortality. The increase in iron serum and ferritin can be used as a diagnosis to warn of the early stage of preeclampsia. The objective of this study was to determine the impact of ferritin serum levels on preeclampsia. This study was an observational analytic study withcase-control design. It has been done from August 2013 to Juli 2014, in RS dr. M. Djamil, RS dr. Reksodiwiryo and Biomedical Laboratory of Andalas University Padang. Total sample evaluated was 40 samples. The sample consist of two groups, each group consist of 20 respondents. Ferritin serum level was examined by using ELISA method. The difference of ferritin serum level between preeclampsia and normal pregnancy analyzed by using independen t test.The result of this study shows that the avarage of ferritin serum levels in preeclampsia group and normalpregnancy is 50,46+4,37 ng/ml and 17,64+1,6  ng /ml, with a p-value 0,004. The ferritin serum level in both groups is normal  and didn’t find that excess iron as a risk factor for preeclampsia. It can be concluded that ferritin serum level has no role on preeclampsia. Keywords: preeclampsia, hypertension in pregnancy, ferritin serum

scholarly journals PIP2 promotes conformation-specific dimerization of the EphA2 membrane region

2020 ◽  
pp. jbc.RA120.016423
Author(s):  
Katherine M Stefanski ◽  
Charles M Russell ◽  
Justin M Westerfield ◽  
Rajan Lamichhane ◽  
Francisco N Barrera
Keyword(s):  
Single Molecule ◽  
Oncogenic Signaling ◽  
Independent States ◽  
Conformational Coupling ◽  
The Difference ◽  
Tm Domain ◽  
Hydrophobic Matching ◽  
The Impact ◽  
Membrane Region ◽  
Positively Charged

The impact of the EphA2 receptor on cancer malignancy hinges on the two different ways it can be activated. EphA2 induces anti-oncogenic signaling after ligand binding, but ligand-independent activation of EphA2 is pro-oncogenic. It is believed that the transmembrane (TM) domain of EphA2 adopts two alternate conformations in the ligand-dependent and the ligand-independent states. However, it is poorly understood how the difference in TM helical crossing angles found in the two conformations impacts the activity and regulation of EphA2. We devised a method that uses hydrophobic matching to stabilize two conformations of a peptide comprising the EphA2 TM domain and a portion of the intracellular juxtamembrane (JM) segment. The two conformations exhibit different TM crossing angles, resembling the ligand-dependent and ligand-independent states. We developed a single-molecule technique using SMALPs to measure dimerization in membranes. We observed that the signaling lipid PIP2 promotes TM dimerization, but only in the small crossing angle state, which we propose corresponds to the ligand-independent conformation. In this state the two TM are almost parallel, and the positively charged JM segments are expected to be close to each other, causing electrostatic repulsion. The mechanism PIP2 uses to promote dimerization might involve alleviating this repulsion due to its high density of negative charges. Our data reveal a conformational coupling between the TM and JM regions, and suggest that PIP2 might directly exert a regulatory effect on EphA2 activation in cells that is specific to the ligand-independent conformation of the receptor.

scholarly journals Safety and Prognostic Impacts of Ovarian Preservation during Radical Hysterectomy for Early-Stage Adenocarcinoma and Adenosquamous Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Arisa Theplib ◽  
Jitti Hanprasertpong ◽  
Kittinun Leetanaporn
Keyword(s):  
Cervical Cancer ◽  
Radical Hysterectomy ◽  
Early Stage ◽  
Pelvic Lymphadenectomy ◽  
Ovarian Metastasis ◽  
Ovarian Preservation ◽  
Oncological Outcomes ◽  
The Difference ◽  
The Impact

Objective. To identify the incidence of ovarian metastasis and the impact of ovarian preservation on oncological outcomes for early-stage adenocarcinoma and adenosquamous cervical cancer. Methods. 281 patients with stages IA2-IB1 adenocarcinoma and adenosquamous cervical cancer who underwent radical hysterectomy with pelvic lymphadenectomy (RHND) were included in the study. The incidence of ovarian metastasis was evaluated from 173 patients who underwent oophorectomy during RHND. Subgroup analysis was performed for patients less than 50 years (196 of 281 patients) who were classified into two groups, ovarian preservation and nonovarian preservation groups. 5-year recurrence-free survival (5-yr RFS) and 5-year overall survival (5-yr OS) were evaluated and compared between these groups. Results. There was no evidence of ovarian metastasis, synchronous ovarian cancer, or ovarian recurrence during follow-up. In patients less than 50 years of age, there were no statistically significant differences in the 5-yr RFS ( P = 0.363 ), or 5-yr OS ( P = 0.974 ) between the ovarian preservation and nonovarian preservation groups. In Kaplan–Meier analysis, the ovarian preservation group seemed to have a slightly better OS in long-term follow-up (after 15 years); however, the difference was not statistically significant. Conclusions. Ovarian preservation was safe in adenocarcinoma and adenosquamous cervical cancer stages IA2-B1. However, the impact of ovarian preservation on oncological outcomes needs to be further investigated.

Evaluation of the impact of public investment programs on social and economic performance of territories

2019 ◽  
pp. 109-123
Author(s):  
I. E. Limonov ◽  
M. V. Nesena
Keyword(s):  
Bayesian Modeling ◽  
Positive Impact ◽  
Public Investment ◽  
Difference In Differences ◽  
The Public ◽  
Export Activity ◽  
Regional Investment ◽  
The Difference ◽  
The Impact ◽  
Development Institution

The purpose of this study is to evaluate the impact of public investment programs on the socio-economic development of territories. As a case, the federal target programs for the development of regions and investment programs of the financial development institution — Vnesheconombank, designed to solve the problems of regional development are considered. The impact of the public interventions were evaluated by the “difference in differences” method using Bayesian modeling. The results of the evaluation suggest the positive impact of federal target programs on the total factor productivity of regions and on innovation; and that regional investment programs of Vnesheconombank are improving the export activity. All of the investments considered are likely to have contributed to the reduction of unemployment, but their implementation has been accompanied by an increase in social inequality.

Mechanically-Tunable Quantum Interference in Ferrocene-Based Single-Molecule Junctions

2020 ◽  
Author(s):  
María Camarasa-Gómez ◽  
Daniel Hernangómez-Pérez ◽  
Michael S. Inkpen ◽  
Giacomo Lovat ◽  
E-Dean Fung ◽  
...  
Keyword(s):  
Single Molecule ◽  
Quantum Interference ◽  
Degrees Of Freedom ◽  
Building Blocks ◽  
Ferrocene Derivative ◽  
Single Molecule Junctions ◽  
Molecule Junction ◽  
Single Molecule Junction ◽  
The Impact ◽  
D Orbitals

Ferrocenes are ubiquitous organometallic building blocks that comprise a Fe atom sandwiched between two cyclopentadienyl (Cp) rings that rotate freely at room temperature. Of widespread interest in fundamental studies and real-world applications, they have also attracted<br>some interest as functional elements of molecular-scale devices. Here we investigate the impact of<br>the configurational degrees of freedom of a ferrocene derivative on its single-molecule junction<br>conductance. Measurements indicate that the conductance of the ferrocene derivative, which is<br>suppressed by two orders of magnitude as compared to a fully conjugated analog, can be modulated<br>by altering the junction configuration. Ab initio transport calculations show that the low conductance is a consequence of destructive quantum interference effects that arise from the hybridization of metal-based d-orbitals and the ligand-based π-system. By rotating the Cp rings, the hybridization, and thus the quantum interference, can be mechanically controlled, resulting in a conductance modulation that is seen experimentally.<br>

The Use of Multimedia and its Impact on Bangladeshi EFL Learners at Tertiary Level

2020 ◽  
Vol 4 (2) ◽  
pp. 150
Author(s):  
Farzana Sharmin Pamela Islam
Keyword(s):  
Language Learning ◽  
Academic Writing ◽  
Teaching And Learning ◽  
English Language ◽  
Capital City ◽  
Tertiary Level ◽  
Language Classroom ◽  
The Difference ◽  
The Government ◽  
The Impact

As 21st century is the era of modern technologies with different aspects, it offers us to make the best use of them. After tape recorder and overhead projector (OHP), multimedia has become an important part of language classroom facilities for its unique and effective application in delivering and learning lesson. Although in many parts of Bangladesh, a South Asian developing country, where English enjoys the status of a foreign language, the use of multimedia in teaching and learning is viewed as a matter of luxury. However, nowadays the usefulness and the necessity of it are well recognized by the academics as well as the government. The study aims to focus on the difference between a traditional classroom void of multimedia and multimedia equipped classrooms at university level by explaining how multimedia support the students with enhanced opportunity to interact with diverse texts that give them more in-depth comprehension of the subject. It also focuses on audio-visual advantage of multimedia on the students’ English language learning. The study has followed a qualitative method to get an in-depth understanding of the impact of using multimedia in an English language classroom at tertiary level. For this purpose, the data have been collected from two different sources. Firstly, from students’ written response to  an open ended question as to their comparative experience of learning  lessons with and without multimedia facilities; and secondly, through  observation of English language classes at a private university of Dhaka, the capital city of Bangladesh. The discussion of the study is limited to  the use of multimedia in English language classroom using cartoons, images and music with a view to enhance students’ skills in academic writing, critical analysis of image and critical appreciation of music. For this purpose, cartoons in English language, images from Google and music from You Tube have got focused discussion in this paper.

Monitoring the Structural Dynamics of U2 snRNA Via Single-Molecule Förster Resonance Energy Transfer

2018 ◽  
Author(s):  
Alexander Carl DeHaven
Keyword(s):  
Energy Transfer ◽  
Structural Dynamics ◽  
Single Molecule ◽  
Conformational Dynamics ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Förster Resonance Energy Transfer ◽  
U2 Snrna ◽  
Folding Dynamics ◽  
The Impact

This thesis contains four topic areas: a review of single-molecule microscropy methods and splicing, conformational dynamics of stem II of the U2 snRNA, the impact of post-transcriptional modifications on U2 snRNA folding dynamics, and preliminary findings on Mango aptamer folding dynamics.

Case study: Prediction and field tests of railway noise and effects of a low-height noise barrier

2020 ◽  
Vol 68 (4) ◽  
pp. 303-314
Author(s):  
Yuna Park ◽  
Hyo-In Koh ◽  
University of Science and Technology, Transpo ◽  
University of Science and Technology, Transpo ◽  
University of Science and Technology, Transpo ◽  
...  
Keyword(s):  
High Speed ◽  
Field Tests ◽  
Residential Areas ◽  
Railway Systems ◽  
Railway Noise ◽  
Sound Levels ◽  
Noise Barrier ◽  
The Difference ◽  
Reduction Effect ◽  
The Impact

Railway noise is calculated to predict the impact of new or reconstructed railway tracks on nearby residential areas. The results are used to prepare adequate counter- measures, and the calculation results are directly related to the cost of the action plans. The calculated values were used to produce noise maps for each area of inter- est. The Schall 03 2012 is one of the most frequently used methods for the production of noise maps. The latest version was released in 2012 and uses various input para- meters associated with the latest rail vehicles and track systems in Germany. This version has not been sufficiently used in South Korea, and there is a lack of standard guidelines and a precise manual for Korean railway systems. Thus, it is not clear what input parameters will match specific local cases. This study investigates the modeling procedure for Korean railway systems and the differences between calcu- lated railway sound levels and measured values obtained using the Schall 03 2012 model. Depending on the location of sound receivers, the difference between the cal- culated and measured values was within approximately 4 dB for various train types. In the case of high-speed trains, the value was approximately 7 dB. A noise-reducing measure was also modeled. The noise reduction effect of a low-height noise barrier system was predicted and evaluated for operating railway sites within the frame- work of a national research project in Korea. The comparison of calculated and measured values showed differences within 2.5 dB.

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