Entropically-driven binding of mithramycin in the minor groove of C/G-rich DNA sequences

Final full-text version available at: http://dx.doi.org/10.1093/nar/gkm037.-- Supplementary Data is available.The antitumour antibiotic mithramycin A (MTA) is a DNA minor-groove binding ligand. It binds to C/G-rich tracts as a dimer that forms in the presence of divalent cations such as Mg2+. Differential scanning calorimetry, UV thermal denaturation, isothermal titration calorimetry and competition dialysis were used, together with computations of the hydrophobic free energy of binding, to determine the thermodynamic profile of MTA binding to DNA. The results were compared to those obtained in parallel using the structurally related mithramycin SK (MSK). The binding of MTA to salmon testes DNA determined by UV melting studies (Kobs = 1.2 (±0.3) x 10^5 M–1) is tighter than that of MSK (2.9 (±1.0) x 10^4 M–1) at 25°C. Competition dialysis studies showed a tighter MTA binding to both salmon testes DNA (42% C + G) and Micrococcus lysodeikticus DNA (72% C + G). The thermodynamic analysis of binding data at 25°C shows that the binding of MTA and MSK to DNA is entropically driven, dominated by the hydrophobic transfer of the antibiotics from solution to the DNA-binding site. Direct molecular recognition between MTA or MSK and DNA through hydrogen bonding and van der Waals contacts may also contribute significantly to complex formation.Supported by a grant from the Spanish Ministry of Education and Science (SAF2005-00551) and the FEDER program of the European Community. This work was carried out within the framework of the Centre de Referencia en Biotecnologia of the Generalitat de Catalunya. Funding to pay the Open Access publication charge was provided by the Ministry of Education and Science and CSIC (Spain).Peer reviewe

Path-building and localization system for mobile robotic platforms based on Raspberry Pi

The paper demonstrates a system for detection of location of robotic platform FESTO Robotino and optimal route building. It processes data from the camera and transmits control signals to the control system of the robot. The whole system is based on Raspberry Pi. It detects robot's current coordinates, current angular rotation, angular difference (difference between current and previous angular rotation) and displacement of the robot in its own coordinate system. It uses an ArUco marker, placed on the top of the mobile robot for that. System also builds an optimal path, when moving from one point of the surface to another, according to the permeability of the surface. The authors set the permeability of testing surfaces. Using that, a weighted graph is built through the centers of particular surfaces, which are detected via an algorithm on Raspberry Pi. The optimal path is constructed through the edges of the graph via modified Dijkstra algorithm

Influence of phase composition on electrophysical properties of barium titanate piezoelectric ceramics

In the present study, we investigated the influence of phase transformations and dielectric properties of barium titanate ceramics. The obtained ceramic samples were sintered at 950 ° C and 1350 ° C. It was revealed that sintering of ceramics at 1350 ° C allows obtaining a stable tetragonal phase at room temperature

ФОРМУВАННЯ ГІДРОДИНАМІЧНОГО РЕЖИМУ В ЗОНІ ВПЛИВУ ВІДВАЛІВ ГІРСЬКИХ ПОРІД ТА ХВОСТОСХОВИЩ

За результатами моделювання з використанням тривимірної чисельної моделі, що комплексно відбиває планово-профільну фільтрацію в межах прони-кних і розділяючих шарів, встановлені закономірності геофільтрації у верхній частині породного масиву на ділянках розташування відвалів гірських порід і хвостосховищ. Виявлений характер впливу гідродинамічного режиму, що формується в умовах гравітаційно-навантаженого породного масиву, на гео-механічний стан прилеглої до об'єктів гірничого виробництва території. По результатам моделирования с использованием трехмерной численной модели, комплексно отражающей планово-профильную фильтрацию в пределах проницаемых и разделяющих слоев, установлены закономерности геофильтрации в верхней части породного массива на участках расположе-ния отвалов горных пород и хвостохранилищ. Определен характер влияния гидродинамического режима, формирующегося в условиях гравитационно-нагруженного породного массива, на геомеханическое состояние прилегаю-щей к объектам горного производства территории. The features of ground water flow have been determined for the top layers of the rock mass in dump tailing areas by numerical simulation using a model reproduc-ing 3D ground water flow within aquifers and confining layers. The impact of the hydrodynamic regime formed in the gravitationally loaded rock mass on geomechanical conditions of the territory affected by mining industry sites has been revealed

International Student Mobility: An Identity Development Task?

Based on the review of literature on internationalization of education and on identity formation pro cesses in young adults, this cross - sectional study aims to investigate to which extent self - perceived dimensions of identity are associated to the main moti vations to study abroad. The participants in this study were 429 international university students of different nationalities. Findings revealed that the motivation to study abroa d for personal growth is strongly associated to the commitment and in - depth e xploration identity processes, whereas the motivation to study abroad with the aim of changing life style and enlarging job opportunities is positively associated with reconsideration of commitment and in - depth exploration. Furthermore, identity achieved s tudents showed the highest motivation to s tudy abroad for personal growth, while the motivation to study abroad to positively change life - styles and work conditions is strongly associated with the positive facet of identity crisis, which is otherwise calle d searching - moratorium status. Based on these results, the present survey provides useful questions and hypothesis for future researc

ХУЛІГАНСТВО ТА ЙОГО ХАРАКТЕРИСТИКА

Abstract BACKGROUND: Temporal lobe gray-white matter abnormalities (GWMA) are frequent morphological aberrances observed on MRI in patients with temporal lobe epilepsy (TLE) in addition to hippocampal sclerosis (HS). OBJECTIVE: To study the influence of temporal pole GWMA on clinical characteristics and seizure outcome in patients with HS operated on for TLE. METHODS: A cohort of 370 patients undergoing surgery for intractable TLE was prospectively collected in an epilepsy surgery data base. Clinical characteristics and seizure outcome of all 58 TLE patients with identified HS and GWMA (group 1) were compared with those of a matched control group of 58 HS patients without GWMA (group 2). Both groups were further subdivided into patients undergoing transsylvian selective amygdalohippocampectomy (sAH) and anterior temporal lobectomy with amygdalohippocampectomy (ATL). RESULTS: The HS plus GWMA patients were significantly younger at epilepsy onset than those without GWMA. In the HS plus GWMA group, 41% of patients were younger than 2 years when they experienced their first seizure in contrast to only 17% of patients with pure HS (P = .004). Seizure outcome was not statistically different between the 2 groups: 75.9% of the patients in group 1 were seizure free (Engel class I) compared with 81% of patients in group 2. Seizure outcome in both groups was about equally successful with selective amygdalohippocampectomy and anterior temporal lobectomy (ns). CONCLUSION: Limited and standard resections in TLE patients with HS are equally successful regardless of the presence of GWMA

Unequal impact of COVID-19 on private and academic neurosurgical workforce: results of an international survey

Background: Since the COVID-19 outbreak several manuscripts regarding neurosurgical practice during this pandemic have been published. Qualitative studies on how the pandemic affected neurosurgeons, with additional focus on their practice, are still scarce. This study's objective was to investigate the impact of COVID-19 on various aspects of the professional and private life of a homogeneous group of international neurosurgeons affiliated to the European Association of Neurosurgical Societies (EANS).Methods: Neurosurgeons from Europe and abroad were invited to participate in an online survey endorsed by the Individual Membership Committee of the EANS. The survey captured a subjective snapshot of the impact of the first wave of the COVID-19 pandemic on EANS members and was advertised through its Institutional website. In addition to departmental data, personal feeling of safety, financial security, local precautions, number of surgeries performed, changes in daily routine, and other practice-related information were inquired. Differences among practice types were closely reviewed.Results: The survey was distributed between April and May 2020: 204 neurosurgeons participated. Participants were typically active EANS members (73%), consultants (57.9%), from university hospitals (64.5%). Elective surgical practice was still ongoing only for 15% of responders, whereas 18.7% of them had already transitioned to COVID-19 and emergency medical services. While 65.7% of participants thought their institutions were adequately prepared, lack of testing for SARS-CoV-2, and scarcity of personal protective equipment were still a matter of concern for most of them. Overall surgical activity dropped by 68% (cranial by 54%, spine by 71%), and even emergencies decreased by 35%. COVID-19 prompted changes in communication in 74% of departments, 44% increased telemedicine by >50%. While most neurosurgeons had concerns about personal and families' health, financial outlook appeared to be gloomy only for private practitioners.Conclusion: The lockdown imposed in many countries by the COVID-19 outbreak called for immediate modification of working routine and resulted in a dramatic decrease of elective surgical procedures. Neurosurgeons share common concerns but were not equally exposed to the personal health and financial dangers of the ongoing pandemic.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Aneurysmal Subarachnoid Hemorrhage in Hospitalized Patients on Anticoagulants—A Two Center Matched Case-Control Study

Objective—Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods—Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results—During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4–5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1–3) after 12 months. Conclusions—Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients

The choice of feedstock for the biodiesel production with optimal physicochemical and low-temperature properties

The transesterification reaction of sunflower, mustard and linseed oil with ethyl alcohol was studied using potassium hydroxide as a catalyst. The physicochemical properties and low-temperature characteristics of the feedstock and obtained products were studied. The most preferred feedstock for the biodiesel fuel production had been determined