bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study on quantitative structure–activity relationship and molecular docking of metalloproteinase inhibitors based on L-tyrosine scaffold
Authors: Abbasi Maryam , Ramezani Fatemeh , Elyasi Maryam , Sadeghi-Aliabadi Hojjat , Amanlou Massoud 
Published: April 2015

Abstract

Background
MMP-2 enzyme is a kind of matrix metalloproteinases that digests the denatured collagens and gelatins. It is highly involved in the process of tumor invasion and has been considered as a promising target for cancer therapy. The structural requirements of an MMP-2 inhibitor are: (1) a functional group that binds the zinc ion, and (2) a functional group which interacts with the enzyme backbone and the side chains which undergo effective interactions with the enzyme subsites.

Methods
In the present study, a QSAR model was generated to screen new inhibitors of MMP-2 based on L–hydroxy tyrosine scaffold. Descriptors generation were done by Hyperchem 8, DRAGON and Gaussian98W programs. SPSS and MATLAB programs have been used for multiple linear regression (MLR) and genetic algorithm partial least squares (GA-PLS) analyses and for theoretical validation. Applicability domain of the model was performed to screen new compounds. The binding site potential of all inhibitors was verified by structure-based docking according to their binding energy and then the best inhibitors were selected.

Results
The best QSAR models in MLR and GA-PLS were reported, with the square correlation coefficient for leave-one-out cross-validation (Q2
LOO) larger than 0.921 and 0.900 respectively. The created MLR and GA-PLS models indicated the importance of molecular size, degree of branching, flexibility, shape, three-dimensional coordination of different atoms in a molecule in inhibitory activities against MMP-2.
The docking study indicated that lipophilic and hydrogen bonding interactions among the inhibitors and the receptor are involved in a ligand-receptor interaction. The oxygen of carbonyl and sulfonyl groups is important for hydrogen bonds of ligand with Leu82 and Ala83. R2 and R3 substituents play a main role in hydrogen bonding interactions. R1 is sited in the hydrophobic pocket. Methylene group can help a ligand to be fitted in the lipophilic pocket, so two methylene groups are better than one. The Phenyl group can create a π-π interaction with Phe86.

Conclusions
The QSAR and docking analyses demonstrated to be helpful tools in the prediction of anti-cancer activities and a guide to the synthesis of new metalloproteinase inhibitors based on L-tyrosine scaffold.
PTHrP-Related Hypercalcaemia in Infancy and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Authors: Kodous Nardeen , Filler Guido , Sharma Ajay Parkash , Van Hooren Tamara Angela 
Published: April 2015

Background: Severe hypercalcaemia is a rare but clinically significant condition in infancy and childhood. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcaemia resulting from a malignancy is rare and only a handful of case reports have outlined its incidence alongside a benign condition. Objectives: To describe the diagnostic workup and management of an infant with hypercalcaemia, renal dysplasia, and elevated PTHrP levels. Design: Case report. Setting: The Victoria Hospital campus of the London Health Sciences Centre in London, Ontario, Canada. Patients: A child with congenital anomalies of the kidneys and urinary tract (CAKUT), stage 2 chronic kidney disease (CKD), and renal dysplasia who presented with severe hypercalcaemia. Measurements: Weight, renal ultrasound, creatinine, cystatin C, eGFR, calcium, urea, bicarbonate, serum sodium, fractional sodium excretion, urine calcium to creatinine ratio, PTH, TSH, Free T4, AM cortisol, HMA, VMA, 25-vitamin D, 1,25 dihydroxy-vitamin D, calcitriol, vitamin A, ACE levels, skull and chest x-rays, alkaline phosphatase, CBC, tumour lysis profile, catecholamine breakdown, whole-body MRI, PTHrP. Methods: Full diagnostic workup and patient management. Patient treated with intravenous hydration, furosemide, calcitonin and CalciLo. Results: PTHrP was elevated and no evidence of a malignancy was found. Treatment consisting of a low-calcium CalciLo diet (in place of breast milk) adequately controlled the patient's hypercalcaemia. Hypercalcaemia associated with CAKUT in infancy is not all that uncommon and was reported in 15/99 infants in another study, most of whom had a suppressed PTH similar to that of our patient. PTHrP was not measured in these cases and may have also been elevated. Limitations: The study is limited in that it is a description of a single patient case. Future measurement of PTHrP in similar patients is necessary to confirm our results. Conclusions: The possibility of elevated PTHrP levels must be considered in patients with known renal dysplasia who are differentially diagnosed with hypercalcaemia.
Current Status of Single-Agent Phase I Trials in Japan: Toward Globalization
Authors: Mizugaki Hidenori , Yamamoto Noboru , Fujiwara Yutaka , Nokihara Hiroshi , Yamada Yasuhide , Tamura Tomohide 
Published: April 2015

Purpose In Japan, phase I trials, except first-in-human trials, are usually initiated from approximately 50% of the maximum-tolerated dose (MTD) or maximum administered dose (MAD) determined during the initial phase I trials in North America and Europe (the West). However, the key findings of phase I trials in Japan and the West, such as dose-limiting toxicity (DLT) profiles and MTD or MAD levels, have not been compared. Patients and Methods We retrospectively analyzed data for patients enrolled onto single-agent phase I trials at the National Cancer Center Hospital between 1995 and 2012. DLT profiles, MTDs, and MADs of single-agent phase I trials in Japan were compared with those from trials in the West that were obtained from the literature. Results A total of 777 patients were enrolled onto 54 single-agent phase I trials, including five first-in-human trials. DLTs were observed in 11.1% of the patients. Importantly, 66.4% of the DLTs were observed within a dose range (80% to 120%) similar to those reported for the trials in the West. The majority of MTDs or MADs could be considered similar between patients, and 80.3% of the drugs had similar MTDs or MADs in the West. Conclusion The toxicity profiles of single-agent phase I agents determined from trials conducted in Japan were comparable to those obtained from trials in the West. We believe that phase I trials in Japan could be conducted over timelines similar to those in the West, allowing for global or parallel phase I clinical trials.
Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease
Authors: Griffin Lindsay M. , Thayu Meena , Baldassano Robert N. , DeBoer Mark D. , Zemel Babette S. , Denburg Michelle R. , Denson Lee A. , Shults Justine , Herskovitz Rita , Long Jin , Leonard Mary B. 
Published: April 2015

Context:
Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-α effects to decrease bone formation and promote bone resorption.

Objective:
This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-α therapy.

Design and Participants:
Participants (n = 74; age 5–21 years) with CD completed a 12-month prospective cohort study.

Main Outcome Measures:
Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-α therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on &gt;650 reference participants.

Results:
At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P &lt; .01). Pediatric CD activity index decreased during the 10-week induction (P &lt; .001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P &lt; .05; others P &lt; .001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P &lt; .001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P &lt; .001). Younger age was associated with greater increases in trabecular BMD z scores (P &lt; .001) and greater linear growth with greater recovery of cortical area (P &lt; .001).

Conclusions:
Anti-TNF-α therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits.
Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease
Authors: Schroer Alison K. , Merryman W. David 
Published: April 2015

ABSTRACTFibrotic cardiac disease, a leading cause of death worldwide, manifests as substantial loss of function following maladaptive tissue remodeling. Fibrosis can affect both the heart valves and the myocardium and is characterized by the activation of fibroblasts and accumulation of extracellular matrix. Valvular interstitial cells and cardiac fibroblasts, the cell types responsible for maintenance of cardiac extracellular matrix, are sensitive to changing mechanical environments, and their ability to sense and respond to mechanical forces determines both normal development and the progression of disease. Recent studies have uncovered specific adhesion proteins and mechano-sensitive signaling pathways that contribute to the progression of fibrosis. Integrins form adhesions with the extracellular matrix, and respond to changes in substrate stiffness and extracellular matrix composition. Cadherins mechanically link neighboring cells and are likely to contribute to fibrotic disease propagation. Finally, transition to the active myofibroblast phenotype leads to maladaptive tissue remodeling and enhanced mechanotransductive signaling, forming a positive feedback loop that contributes to heart failure. This Commentary summarizes recent findings on the role of mechanotransduction through integrins and cadherins to perpetuate mechanically induced differentiation and fibrosis in the context of cardiac disease.
School leadership for equity and learning and the question of school autonomy
Authors: Hatzopoulos Pavlos , Kollias Andreas , Kikis-Papadakis Kathy 
Published: April 2015

Artikkel põhineb koolijuhtimise Euroopa võrgustiku (EPNoSL) raames tehtud tööl, eelkõige 21 Euroopa riigi koolijuhtimise strateegiate süvauuringul ja aruteludel, mis toimuvad EPNoSLi veebiseminaridel, riikide õpikodades ja vastastikuse õppe üritustel, millest võtavad osa mitmes ELi riigis koolijuhtimisega seotud huvirühmad (sh Euroopa, riikliku ja kohaliku tasandi poliitikakujundajad, koolijuhid, õpetajad ja teised haridustöötajad, õppejõud, lapsevanemad ja õpilased). EPNoSL on Euroopas tegutsevast 42 institutsioonist koosnev võrgustik, mille eesmärk on parandada Euroopa koolide juhtimist nii poliitilisel kui ka praktilisel tasandil. Artiklis käsitletakse koolide autonoomia küsimust Euroopa koolijuhtimise strateegiate kujundamise kontekstis. Koolide autonoomiat peetakse tervikliku koolijuhtimise poliitika väljatöötamise oluliseks eeltingimuseks. Artikkel tugineb kõnealuse projekti raames välja töötatud laiaulatuslikule koolijuhtimise strateegia kujundamise raamistikule ja sellel on kaks põhieesmärki. Esiteks püütakse artiklis näidata, et selle asemel et otsida koolide autonoomia puhul ühte, kõigile sobivat lahendust, tuleks keskenduda konkreetset olukorda arvestavale strateegiale, mille eesmärk on saavutada kindlaksmääratud õpitulemused ja võrdsed võimalused. Teiseks on artiklis kirjeldatud seitset koolide autonoomia põhisuunda, mida on võimalik kohandada Euroopa eripalgeliste haridussüsteemidega.
Full text
Methodological challenges and choices when identifying EU related training needs of Estonian public service
Authors: Veebel Viljar , Kulu Liina , Hurt Ulrika 
Published: April 2015

Artiklis analüüsitakse Eesti avaliku sektori töötajate koolitusvajaduse hindamisega seotud metodoloogilisi sõlmküsimusi, tuginedes aastatel 2002–2013 ametnike ja poliitikute seas korraldatud Euroopa Liidu alase koolitusvajaduse uuringutele. Sarnaste uuringute kaudu koolitusvajaduse kindlaksmääramisel on keskse tähtsusega kolm aspekti. Esiteks, uuring peaks olema keskendunud just koolitusvajaduse, mitte aga igapäevatöös oluliste teemade, koolitussoovide vms väljaselgitamisele. Teiseks, uuringut ette valmistavas faasis tuleb välistada tulemuste kalibreerimine, kus vastajaid suunatakse nn ohtlikele küsimustele vastama uuringu tellija jaoks sobival viisil. Kolmandaks on soovitatav peale küsitluspõhise uurimismeetodi kasutada ka mõõdetavat teadmiste kontrolli vormi (nt testi), mis võimaldab objektiivselt tuvastada vastaja kalduvust teadmisi ja oskusi üle- või alahinnata (nn Dunningi-Krugeri efekt).
Summary
From the borders to centre stage: Photographic self-portraiture
Authors: Kalpaxi Elisavet 
Published: April 2015

Abstract
This article examines photographic self-portraiture and investigates what happens when the genre’s proximity to conceptual borders – between the centre and the margins, self and other, normal and deviant behaviour, consciousness and unconsciousness – are crossed. Drawing on psychoanalytic and semiotic theories, and the history of the self-portrait, this article investigates the negativity ascribed to self-portraiture, its association with identity politics and social media, and problems of reference arising in contemporary artworks. The article starts out from the premise that the objectification of one’s body image is inherently linked to narcissism. This idea is useful for understanding the meaning of the photo-album/photo-diary, the therapeutic aspects of self-portraiture, and the rhetoric applied to images produced to bring visibility to marginalized and under-represented groups, which also serve to challenge the art establishment. However, the prioritization of art as a context for photography, the popularity of the genre, and the changing ideas related to definitions of ‘the centre’ in these contexts, demand that the conceptual character of the representation of selfhoods be redefined.
QUALIDADE MICROBIOLÓGICA DA ÁGUA UTILIZADA EM PROPRIEDADES LEITEIRAS
Authors: Rangel Adriano Henrique do Nascimento , Freire Rayssa Maria Bezerril , Borba Luís Henrique Fernandes , Lima Júnior Dorgival Morais de , Novaes Luciano Patto 
Published: April 2015

Objetivou-se avaliar a qualidade microbiológica de amostras de água de poço utilizada na ordenha, além de verificar sua influência na contagem bacteriana total (CBT) do leite obtido em propriedades no estado do Rio Grande do Norte. Amostras de 1.000 mL de água do poço e da água utilizada na ordenha foram coletadas em recipientes estéreis e realizadas análises de coliformes totais e termotolerantes, pelo método de membrana filtrante. Amostras da água do poço apresentaram valores de 21.250 UFC/100 mL para coliformes totais e 12.269 UFC/100 mL para coliformes termotolerantes e as amostras da água da ordenha apresentaram valores de 5.520 UFC/100 mL para coliformes totais e 3.483 UFC/100 mL para coliformes termotolerantes. A detecção de coliformes nas amostras analisadas afetou a qualidade microbiológica do leite avaliada por meio da CBT. Constatou-se que a qualidade microbiológica da água utilizada nas propriedades leiteiras apresenta-se fora do preconizado pelo Ministério da Saúde para uso na higienização dos equipamentos e consumo pelos animais e seres humanos, quanto aos padrões de potabilidade.
ENUMERAÇÃO DE MICRORGANISMOS PSICROTRÓFICOS E TERMODÚRICOS PSICROTROFICOS DE LEITE: COMPARAÇÃO DE METODOLOGIAS
Authors: Beloti Vanerli , Ribeiro Júnior José Carlos , Tamanini Ronaldo , Araújo João Paulo Andrade de , Yamada Alberto Koji , Antônio Nayara Da Silva 
Published: April 2015

O objetivo do presente trabalho foi avaliar se o binômio temperatura/tempo de 21 ºC por 25 horas, já validado para enumeração de psicrotróficos em leite, apresenta viabilidade para enumeração de termodúricos psicrotróficos, comparando as contagens dos psicrotróficos e dos termodúricos psicrotróficos obtidas em cada binômio de tempo e temperatura de incubação. Foram avaliadas 28 amostras de leite cru refrigerado coletadas em tanques de caminhões transportadores na plataforma de recepção de um laticínio no norte do Paraná. Foram enumerados psicrotróficos e termodúricos psicrotróficos à 7 ºC por 10 dias e a 21 ºC por 25 horas. Para os psicrotróficos, foi observado que não houve diferença significativa das contagens comparando os dois métodos de incubação (p = 0,46), o coeficiente de correlação entre os métodos foi de 0,90 e a regressão linear considerada satisfatória. Para os termodúricos psicrotróficos, também não foi observada diferença significativa (p = 0,17) nas contagens, porém, o coeficiente de correlação entre os dois métodos foi de 0,69 e a regressão linear insatisfatória. Foi observada também maior homogeneidade na distribuição dos resultados das contagens de psicrotróficos em relação aos termodúricos psicrotróficos. Os resultados demonstram que a enumeração de microrganismos termodúricos psicrotróficos pela metodologia mais rápida não é adequada, uma vez que o coeficiente de correlação e a regressão linear dos métodos são baixos.
Processing and Properties of Distaloy Sa Sintered Alloys with Boron and Carbon
Authors: Karwan-Baczewska J. 
Published: April 2015

Abstract
Prealloyed iron-based powders, manufactured in Höganäs Company, are used in the automotive parts industry. The properties and life time of such sintered parts depend, first of all, on their chemical composition, the production method of the prealloyed powder as well as on the technology of their consolidation and sintering. One of simpler and conventional methods aimed at increasing the density in sintered products is the process of activated sintering, performed, for example, by adding boron as elementary boron powder. Under this research project obtained were novel sintered materials, based on prealloyed and diffusion bonded powder, type: Distaloy SA, with the following chemical composition: Fe-1.75% Ni-1.5%Cu- 0.5%Mo with carbon (0.55%; 0.75%) and boron (0.2%, 0.4% and 0.6%). Distaloy SA samples alloyed with carbon and boron were manufactured by mixing powders in a Turbula mixer, then compressed using a hydraulic press under a pressure of 600 MPa and sintered in a tube furnace at 1473 K, for a 60 minute time, in the hydrogen atmosphere. After the sintering process, there were performed density and porosity measurements as well as hardness tests and mechanical properties were carried out, too. Eventually, analyzed was the effect of boron upon density, hardness and mechanical properties of novel sintered construction parts made from Distaloy SA powder.
Fatigue Damage of Al/SiC Composites - Macroscopic and Microscopic Analysis
Authors: Rutecka A. , Kowalewski Z.L. , Makowska K. , Pietrzak K. , Dietrich L. 
Published: April 2015

Abstract
The results of comparative examinations of mechanical behaviour during fatigue loads and microstructure assessment before and after fatigue tests were presented. Composites of aluminium matrix and SiC reinforcement manufactured using the KoBo method were investigated. The combinations of two kinds of fatigue damage mechanisms were observed. The first one governed by cyclic plasticity and related to inelastic strain amplitude changes and the second one expressed in a form of ratcheting based on changes in mean inelastic strain. The higher SiC content the less influence of the fatigue damage mechanisms on material behaviour was observed. Attempts have been made to evaluate an appropriate fatigue damage parameter. However, it still needs further improvements.
Tem Study of Recrystallization in Ultra-Fine Grain AA3104 Alloy Processed by High-Pressure Torsion
Authors: Paul H. , Morawiec A. , Baudin T. , Czeppe T. 
Published: April 2015

AbstractThe effect of annealing on the microstructure and the texture development was investigated in a particle containing AA3104 aluminium alloy. The samples were processed at room temperature by high-pressure torsion (HPT) up to ten turns. The nucleation of new grains was analyzed by a transmission electron microscope equipped with a system for local orientation measurements and a heating holder.The shear deformation induces a decrease of the grain size. After the first two turns of the HPT processing the initial structure of large grains was ‘transformed’ into a structure of fine cells/grains with the diameter of a few tens of nanometers. In the central areas of the samples the elongated shape of the cells/grains was observed up to six turns. For higher deformations, this structural inhomogeneity was totally removed and only the equiaxed grains were observed. The crystal lattice of small grains rotates in such a way that the <111> direction is parallel to the compression axis. After annealing the structure coarsened. Nevertheless, after primary recrystallization, the structure was still composed of relatively fine and equiaxed grains of a similar size. In most of the observed cases the size of the recrystallized grains in the areas close to and far from the large second phase particles was similar. The recrystallization leads to the creation of new texture components. The new grain orientations lost the positions typically observed in the deformed state and showed the tendency for the coincidence of the <100> crystallographic directions with the compression axis.
The Study of the Impact of Surface Preparation Methods of Inconel 625 and 718 Nickel-Base Alloys on Wettability by BNi-2 and BNi-3 Brazing Filler Metals
Authors: Lankiewicz K. , Baranowski M. , Babul T. , Kowalski S. 
Published: April 2015

Abstract
The article discusses the impact of surface preparation method of Inconel 625 and 718 nickel-base alloys in the form of sheets on wettability of the surface. The results of the investigations of surface preparation method (such as nicro-blasting, nickel plating, etching, degreasing, abrasive blasting with grit 120 and 220 and manually grinding with grit 120 and 240) on spreading of BNi-2 and BNi-3 brazing filler metals, widely used in the aerospace industry in high temperature vacuum brazing processes, are presented. Technological parameters of vacuum brazing process are shown. The macro- and microscopic analysis have shown that nicro-blasting does not bring any benefits of wettability of the alloys investigated.
The Influence of Strontium on the Microstructure of Cast Magnesium Alloys Containing Aluminum and Calcium
Authors: Rzychoń T. , Dybowski B. , Kiełbus A. 
Published: April 2015

Abstract
The structure of Mg-9Al-2Ca-xSr alloys is composed of a-Mg grains and the Al2Ca and Al4 Sr phases in the interdendritic areas. These phases are formed as a result of eutectic reactions. Globular particles of the Al8Mn5 phase are observed within the interior of the grains. The addition of strontium to Mg-9Al-2Ca-0.4Mn alloys causes the formation of the Al4Sr phase and increase of its volume fraction with increasing strontium levels. Moreover, increase of the strontium amount causes a decrease of aluminum content in the a-Mg solid solution.
Empirical Formulae for The Calculation of Austenite Supercooled Transformation Temperatures
Authors: Trzaska J. 
Published: April 2015

Abstract
The paper presents empirical formulae for the calculation of austenite supercooled transformation temperatures, basing on the chemical composition, austenitising temperature and cooling rate. The multiple regression method was used. Four equations were established allowing to calculate temperature of the start area of ferrite, perlite, bainite and martensite at the given cooling rate. The calculation results obtained do not allow to determine the cooling rate range of ferritic, pearlitic, bainitic and martensite transformations. Classifiers based on logistic regression or neural network were established to solve this problem.