496 research outputs found

    Europe as International Actor: Maximizing Nation-State Sovereignty. CES Germany & Europe Working Papers, No. 06.3, 1996

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    The continually increasing literature on foreign- and security-policy dimensions of the European Union (EU) has provided no remedy for the widespread helplessness in gaining a purchase on Europe as an international actor. The basic hindrance to understanding this policy comes from an all-too-literal interpretation of the acronym involved: the CFSP is understood as a total or partial replacement of the nation-states' foreign and security policy. This article aims to point the way to a new understanding of the CFSP in which this policy is not based on the integration of nation­ state foreign and security policy. I suggest that the proper way to grasp the phenomenon of the CFSP is to describe it as an international regime whose goal is to administer links between economic integration and foreign- and security­ policy cooperation in the sense of maximizing the sovereignty of member states. This requires, on the one hand, the prevention of "spillovers" from the economic area that could interfere with the foreign- and security-policy indepen­ dence of member states. On the other hand, it demands applying the EU's economic potential to reinforce the foreign- and security-policy range of member states. Due to the logic of this policy, CFSP priorities and fields of ac­ tion differ profoundly from those of a national foreign and security policy. Expectations on the evolution of the CFSP must be aware of these basic characteristics of this policy

    A Correlational and Causal Comparative Study of the First-Year Retention of Special Admissions Students

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    College retention has been widely studied since it is an important indicator of institutional effectiveness; however, though higher education institutions have focused on factors that increase retention and graduation rates, many students who enter college do not persist to graduation. To increase the retention of all students, both regular admissions and special admissions, many institutions have implemented programs, like first-year seminars, to help students successfully academically and socially transition to college, which are important factors in first-year retention. The purpose of this correlational and causal comparative study was to determine the most significant predictor of first-year retention for special admissions students: high school grade point average, college entrance exam scores, or institutional commitment. The study also sought to determine the effectiveness of a first-year seminar on the first-year retention of special admissions students. Using logistic regression testing, the researcher tested the predictive value of the predictor variables to the outcome variable, college retention. The results indicated no statistical significance for high school grade point average, entrance exam scores, or institutional commitment to predict first-year retention. Using a Chi-Square test, the researcher tested for the differences in first-year retention between regular admission and special admission students. The results of this study present many implications for those who seek to increase first-year retention for academically at-risk students. It appears as if Tinto’s (1975) theory of departure was correct in presenting that persistence decisions are individual in nature based on independent student factors

    An Amyloid-Like Pathological Conformation of TDP-43 Is Stabilized by Hypercooperative Hydrogen Bonds

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    TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional RNA regulatory assemblies as well as pernicious aggregation. Evidence from pathological mutations and seeding experiments strongly suggest that TDP-43 aggregates are pathologically relevant through toxic gain-of-harmful-function and/or harmful loss-of-native-function mechanisms. Recent, but not early, microscopy studies and the ability of TDP-43 aggregates to resist harsh treatment and to seed new pathological aggregates in vitro and in cells strongly suggest that TDP-43 aggregates have a self-templating, amyloid-like structure. Based on the importance of the Gln/Asn-rich 341–367 residue segment for efficient aggregation of endogenous TDP-43 when presented as a 12X-repeat and extensive spectroscopic and computational experiments, we recently proposed that this segment adopts a beta-hairpin structure that assembles in a parallel with a beta-turn configuration to form an amyloid-like structure. Here, we propose that this conformer is stabilized by an especially strong class of hypercooperative hydrogen bonding unique to Gln and Asn sidechains. The clinical existence of this conformer is supported by very recent LC-MS/MS characterization of TDP-43 from ex vivo aggregates, which show that residues 341–367 were protected in vivo from Ser phosphorylation, Gln/Asn deamidation and Met oxidation. Its distinct pattern of SDS-PAGE bands allows us to link this conformer to the exceptionally stable seed of the Type A TDP-43 proteinopathy.This work was supported by Grants SAF2013-49179-C2-2-R (DVL) and EU JPND AC14/00037 (DVL) and EU JPND RiModFTD, Italy, Ministero della Sanita’ (EB), and the Thierry Latran Foundation REHNPALS (EB).Peer reviewedPeer Reviewe

    PENGARUH PERILAKU KEPEMIMPINAN TERHADAP MOTIVASI KERJA KARYAWAN PADA BAGIAN PRODUKSI PT. VICTORI GARMENTEX

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    Masalah yang dikaji dalam penelitian ini adalah belum optimalnya motivasi kerja karyawan PT. Victori Garmentex, yang ditandai dengan hasil penilaian kinerja karyawan yang belum optimal. Penelitian ini terdiri dari dua variabel yaitu Perilaku Kepemimpinan dan Motivasi Kerja Karyawan. Penelitian ini betujuan untuk mengetahui gambaran perilaku kepemimpinan, untuk mengetahui gambaran tingkat motivasi kerja karyawan dan untuk mengetahui seberapa besar pengaruh perilaku kepemimpinan terhadap motivasi kerja karyawan. Metode penelitian yang digunakan adalah metode survey. Teknik pengumpulan data yang digunakan adalah wawancara dan penyebaran angket dengan menggunakan skala pengukuran rating scale. Teknik analisis data yang digunakan adalah analisis regresi sederhana. Ukuran sample dalam penelitian ini adalah 56 orang karyawan PT. Victori Garmentex. Berdasarkan hasil penelitian di PT. Victori Garmentex, diperoleh informasi bahwa perilaku kepemimpinan memiliki pengaruh yang positif dan cukup terhadap motivasi kerja karyawan. Nilai koefisien korelasi yang diperoleh menunjukkan bahwa terdapat korelasi yang cukup kuat antara perilaku kepemimpinan dan motivasi kerja karyawan. The problem that was studied in this research is not yet optimal work motivation of employee PT. Victori Garmentex, it was characterized by the results which is not optimal of measurement of the employee work motivation. The research consist of two variables, they are leadership behavior and work motivation of employee. The purpose of this research is to describe the leadership behavior, to describe the level of work motivation of employee and to determine how much the the leadership behavior on work motivation of the employee. The method of the research in this study is by using survey method. The data collection techniques were used in this research by using interview and questionnaires using a rating scale measurement. The data analysis technique was used the simple regression analysis. The sample in this research are 56 employees PT. Victori Garmentex. Based on the results of PT. Victori Garmentex, was obtained information that the leadership behavior has a positive and enough influence on work motivation of employee. Correlation coefficient values obtained that indicate strong enough correlation leadership behavior and work motivation of employe

    The Evolution of Minimally Invasive Techniques in Restoration of Colonic Continuity

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    Restoration of bowel continuity after Hartmann’s procedure is considered technically challenging and is associated with high morbidity and mortality. This is the main reason why restoration of intestinal continuity is often not attempted. Over the past decade, considerable international experience has gained on this topic with new minimally invasive techniques being developed. This review details the evolution of minimally invasive techniques in restoration of colonic continuity after Hartmann’s procedure. A comprehensive search of PubMed and Embase was done. Different restoration modalities were included. Eight studies, from six different countries, in which multiport laparoscopic restoration of continuity was compared to conventional open restoration of bowel continuity, were included. In the total of 254 patients, continuity was restored laparoscopically compared with 255 patients in which continuity was performed in open fashion. Restoration of bowel continuity via trephine access was also reported; three studies including 37 patients were included in this review. Single-port restoration of bowel continuity after Hartmann’s procedure is a natural evolution of multiport laparoscopy and trephine access. Six studies reporting on single-port reversal of Hartmann’s procedure were included with a total of 75 patients. Single-port access in combination with a transanal approach has also been reported; however, data are extremely limited as there is only one study in the published literature. Success of restoration of bowel continuity with less morbidity and mortality has been demonstrated throughout the evolution of the different surgical techniques. In this review advantages of different approaches for restoration of bowel continuity after Hartmann’s procedure are discussed. Furthermore, surgical techniques are described, pictorial guides are added for some techniques, and flowcharts are given for easy use during clinical decision-making

    Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation

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    Grant BBM_TRA_0203 PD/BD/148028/2019 UIDB/04378/2020The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Ca, 13Cb, 1Ha, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated a-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca21, but do bind Zn21, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested.publishersversionpublishe

    Implications for phase separation

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    Funding Information: The authors would also like to acknowledge Prof. Dr. Jaime Mota, Dra. Irina Franco for the technical assistance with the microscopic experiments, Philip O'Toole for the aid in protein production and Dr. Aldino Viegas and Dr. David Pantoja-Uceda for the support and valuable discussions regarding NMR spectroscopy. This work was supported by Fundação para a Ciência e a Tecnologia (FCT-Portugal) for funding UCIBIO project (UIDP/04378/2020 and UIDB/04378/2020) and Associate Laboratory Institute for Health and Bioeconomy – i4HB Project (LA/P/0140/2020). The authors also thank FCT-Portugal for the PhD grant attributed to SF (PD/BD/148028/2019) under the PTNMRPhD Program. JO is a recipient of a Leonardo Grant from the Spanish BBVA Foundation (BBM_TRA_0203) and a Ramón y Cajal Grant (RYC2018-026042-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future.”) JO and DVL are supported by the Spanish Grants PID-2019-109276RA-I00 and PID-2019-109306RB-I00, respectively, both funded by MCIN/AEI/10.13039/501100011033. The NMR spectrometers are part of the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The 800 MHz spectrometer present in the “Manuel Rico” NMR laboratory (LMR-CSIC) is a node of the Spanish Large-Scale National Facility (ICTS R-LRB-MR). Publisher Copyright: © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.The mediation of liquid–liquid phase separation (LLPS) for fused in sarcoma (FUS) protein is generally attributed to the low-complexity, disordered domains and is enhanced at low temperature. The role of FUS folded domains on the LLPS process remains relatively unknown since most studies are mainly based on fragmented FUS domains. Here, we investigate the effect of metabolites on full-length (FL) FUS LLPS using turbidity assays and differential interference contrast (DIC) microscopy, and explore the behavior of the folded domains by nuclear magnetic resonance (NMR) spectroscopy. FL FUS LLPS is maximal at low concentrations of glucose and glutamate, moderate concentrations of NaCl, Zn2+, and Ca2+ and at the isoelectric pH. The FUS RNA recognition motif (RRM) and zinc-finger (ZnF) domains are found to undergo cold denaturation above 0°C at a temperature that is determined by the conformational stability of the ZnF domain. Cold unfolding exposes buried nonpolar residues that can participate in LLPS-promoting hydrophobic interactions. Therefore, these findings constitute the first evidence that FUS globular domains may have an active role in LLPS under cold stress conditions and in the assembly of stress granules, providing further insight into the environmental regulation of LLPS.publishersversionpublishe

    Chemical Studies on the Stability of Soil Aggregates : Change in Permeability of Soil Aggregate Column Induced bu Percolating with Neutral and Alkaline Solution

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    既報の結果に基づいて推論した粒団生成に関与する成分が, 果して土粒子の耐水性連結にいかなる役割を演じているかを明らかにする研究の一環として, 静置状態で土壌粒団に中性ならびにアルカリ性の溶液を透過させて土壌から特定の成分の離脱を試み, その場合に起こる粒団の崩壊と土壌の持つ透液性の変移をしらべた。1. 主として水溶性と置換性の成分を土壌から溶脱する機能のある0.05N塩化ナトリウム溶液を土壌粒団に透過させると土壌粒団の崩壊ならびに透液性の低下は極めて少なかった。したがって, 置換性塩基類は粒団の安定性に対し大きな役割を果していないことが明らかになった。2. アルカリ性の腐植抽出剤である0.5%水酸化ナトリウム溶液を土壌粒団に透過させると, 粒団の崩壊が著しく, それに応じて土壌の持つ透液性も低下した。しかし, 土壌からの腐植の離脱量と透液性の低下との間に認められた相関は高くないので粒団の安定性は腐植の単独作用によって律せられるものでないことがわかった。この際同時にアルミニウムがかなり多量に離脱され, これが粒団の安定性に関与することが類推された。3. 中性の腐植抽出剤である0.1Mピロ燐酸ナトリウム溶液を土壌粒団に透過させると, 土壌の種類によってその程度はかなり異なるが概して粒団崩壊と透液比の低下は大きかった。ところが, 土壌から離脱した腐植量と透液比の低下との間には相関が見出せなかった。ピロ燐酸ナトリウム溶液は土壌から腐植と同時に鉄, アルミニウム, カルシウムなどの無機成分を溶脱し, これらの正電荷を抑えて土粒の分散を促がす機能が高いから, この場合の粒団の崩壊はとくに同時に離脱する鉄やアルミニウムによるところが大きいと考えられる。 / With the object to determine the kinds of binding materials in soil aggregates and the part played by each of them, experiments were made on the effect of percolation with neutral or alkaline solution on the aggregate stability. The results obtained are as follows : 1) Aggregates were not greatly affected by the treatment with 0.05N sodium chloride solution. Hence, the part played by exchangeable bases appeared not large in the stabilization of aggregates. 2) When 0.5% sodium hydroxide solution was passed through the column to remove humus from aggregates, the permeability was remarkably lowered. But since the amount of humus removed was not so closely related to the degree of lowering in permeability, the aggregate stability did not seem attributable to the function of humus alone. It was suggested that aluminum removed from aggregates in a large amount in addition to humus participates in their stability. 3) When treated with 0.1M sodium pyrophosphate solution, neutral reagent for humus extraction, the aggregates were markedly broken down and their permeability was greatly lowered, though not without some differences in the extent of effect among the kinds of soil. On the other hand, no distinct correlation was found between the amount of humus removed and the degree of lowering in permeability ratio (the ratio of the permeability at any given time after treatment, Pt, to the initial permeability, Pi). In this case, inorganic components such as aluminum and iron, which were removed by sodium pyrophosphate solution in addition to humus, were considered to be intimately concerned with the result. 4) From these results, it may be indicated that the part played by the combined action of humus and aluminum or iron is important for the stability of soil aggregates

    Nanotechnology in Metformin Delivery: Fasting Blood Glucose and Neutrophil-Lymphocyte Ratio of Diabetic Rat Model

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    Diabetes Mellitus (DM) is a chronic inflammatory disease characterized by hyperglycemia and increasing the neutrophil-lymphocyte ratio (NLR). Metformin has been widely used to treat hyperglycemia. Metformin nanoparticles can improve bioavailability and may reduce inflammation. This study aims to analyze the effectiveness of metformin nanoparticles delivery through fasting blood glucose (FGB) level and NLR in the diabetic rat model. This study used 16 white male Wistar rats, 8 weeks of age, and body weight (BW) 250-350 grams. The streptozotocin (STZ) 40 mg/kg BW were injected i.p. Rats were divided into 4 groups; K1: normal control; K2: negative control (diabetes model); K3: diabetes model treated with metformin 100mg/Kg BW; K4: diabetes model treated with nanoparticle metformin 100mg/kg BW. Blood analysis tests were conducted using the Pentra hematology analyzer. Data were analyzed using the Graphpad Prism program with the nonparametric Kruskal Wallis test. The K3 group showed a periodical decrease in FBG level from day 7 to day 28 by 122 ± 11.31 mg/dL, and the mean NLR value was 0.48 ± 0.3 x 103/uL. Group of K4 periodically decreased in FBG level, indicating that it was closer to normal than K3. The result showed that at day 28.79 ± 15.39 mg/dL, the mean NLR value slightly increased compared to the K3 group by 0.54 ± 0.3 x103/uL. The statistical tests showed a significant difference between the level of FBG (p 0.0089) but no significant difference in NLR (p 0.347). Metformin nanoparticles could decrease FBG levels and effectively reduce the NLR in the diabetic rat model
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