The impact of alkyl chain purity on lipid based nucleic acid delivery systems – is the utilization of lipid components with technical grade justified?

The physicochemical properties and transfection efficacies of two samples of a cationic lipid have been investigated and compared in 2D (monolayers at the air/liquid interface) and 3D (aqueous bulk dispersions) model systems using different techniques. The samples differ only in their chain composition due to the purity of the oleylamine (chain precursor). Lipid 8 (using the oleylamine of technical grade for cost-efficient synthesis) shows lateral phase separation in the Langmuir layers. However, the amount of attached DNA, determined by IRRAS, is for both samples the same. In 3D systems, lipid 8 p forms cubic phases, which disappear after addition of DNA. At physiological temperatures, both lipids (alone and in mixture with cholesterol) assemble to lamellar aggregates and exhibit comparable DNA delivery efficiency. This study demonstrates that non-lamellar structures are not compulsory for high transfection rates. The results legitimate the utilization of oleyl chains of technical grade in the synthesis of cationic transfection lipid

The microwave cavity perturbation technique for contact-free and in situ electrical conductivity measurements in catalysis and materials science

We have developed a noncontact method to probe the electrical conductivity and complex permittivity of single and polycrystalline samples in a flow-through reactor in the temperature range of 20–500 °C and in various gas atmospheres. The method is based on the microwave cavity perturbation technique and allows the simultaneous measurement of microwave conductivity, permittivity and of the catalytic performance of heterogeneous catalysts without any need for contacting the sample with electrodes. The sensitivity of the method towards changes in bulk properties was proven by the investigation of characteristic first-order phase transitions of the ionic conductor rubidium nitrate in the temperature range between 20 and 320 °C, and by studying the temperature dependence of the complex permittivity and conductivity of a niobium(V)-doped vanadium-phosphorous-oxide catalyst for the selective oxidation of n-butane to maleic anhydride. Simultaneously, the catalytic performance was probed by on line GC analysis of evolving product gases making the technique a real in situ method enabling the noninvasive investigation of electronic structure–function relationships

Structure Formation and Coupling Reactions of Hexaphenylbenzene and Its Brominated Analog

The on-surface coupling of the prototypical precursor molecule for graphene nanoribbon synthesis, 6,11-dibromo-1,2,3,4-tetraphenyltriphenylene (C42Br2H26, TPTP), and its non-brominated analog hexaphenylbenzene (C42H30, HPB), was investigated on coinage metal substrates as a function of thermal treatment. For HPB, which forms non-covalent 2D monolayers at room temperature, a thermally induced transition of the monolayer’s structure could be achieved by moderate annealing, which is likely driven by π-bond formation. It is found that the dibrominated carbon positions of TPTP do not guide the coupling if the growth occurs on a substrate at temperatures that are sufficient to initiate C--H bond activation. Instead, similar one-dimensional molecular structures are obtained for both types of precursors, HPB and TPTP

The directional observation of highly dynamic membrane tubule formation induced by engulfed liposomes

Highly dynamic tubular structures in cells are responsible for exchanges between organelles. Compared with bacterial invasion, the most affordable and least toxic lipids were found in this study to be gentle and safe exogenous stimuli for the triggering of membrane tubules. A specific lipid system was internalized by NIH3T3 cells. Following cellular uptake, the constructed liposomes traveled towards the nucleus in aggregations and were gradually distributed into moving vesicles and tubules in the cytosol. The triggered tubules proceeded, retreated or fluctuated along the cytoskeleton and were highly dynamic, moving quickly (up to several microns per second), and breaking and fusing frequently. These elongated tubules could also fuse with one another, giving rise to polygonal membrane networks. These lipid systems, with the novel property of accelerating intracellular transport, provide a new paradigm for investigating cellular dynamics

Descritores para a proteção de cultivares de araucária.

Araucaria angustifolia (Bert.) O. Ktze, é uma espécie icônica e de grande importância para o Brasil, principalmente para a região Sul. Conhecida popularmente como araucária, pinheiro brasileiro ou pinheiro do Paraná, originalmente cobria grandes áreas na região Sul, estendendo-se para São Paulo, Minas Gerais, Rio de Janeiro e Espírito Santo em pequenas manchas isoladas, principalmente em regiões de maior altitude destes estados (Carvalho, 2003). Desde os primórdios da ocupação do território brasileiro onde ocorre, a araucária sempre manteve papel chave na sobrevivência humana, fornecendo madeira para construções e outros usos, bem como o pinhão para a alimentação (Wendling e Zanette, 2017)

Изменение вентиляционной функции легких в процессе формирования хронической обструктивной болезни легких и при ее сочетании с раком легкого

Aim. To study the ventilation function of the lungs in patients with varying degrees of severity of chronic obstructive pulmonary disease (COPD) and in patients with COPD combined with lung cancer (LC), as well as to establish the features of its disorders using spirography and body plethysmography.Materials and methods. A clinical and functional study of 57 individuals was carried out with 10 healthy patients (control group), 30 patients with COPD and 17 patients in whom LC was combined with COPD using the Masterlab Pro diagnostic complex (Erich Jaeger, Germany).Results. In patients with early COPD, a decrease in MEF75 (a ventilation parameter characterizing small airway patency) is the most informative. With the progression of bronchial obstruction, both restrictive and obstructive disorders, characterized by a decrease in FEV1, VC, a change in the structure of the total lung capacity in the form of an increase in the RV/TLC ratio such as an increase in the RV/TLC ratio and an increase in bronchial resistance were recorded. In patients with LC and mild COPD, pulmonary volumes, capacities, flow-volume loop and bronchial resistance parameters did not differ from patients with COPD with a similar bronchial obstruction. In patients with LC and more severe COPD, in contrast to patients suffering from a similar severity of COPD, a decrease in the patency of large, medium and small diameter bronchi (PEF, MEF25, MEF50, MEF75) was detected, which indicated development of generalized bronchial obstruction.Conclusion. Modern diagnostics of pulmonary ventilation disorders in patients with LC and COPD should be aimed at identifying the disease, and drug therapy should target maximum leveling of reversible components of bronchial obstruction in order to increase the functional reserve of the respiratory system and reduce the risk of postoperative complications caused by COPD.Цель. Изучение вентиляционной функции легких у пациентов с различной степенью тяжести хронической обструктивной болезни легких (ХОБЛ) и при ее сочетании с раком легкого (РЛ), а также установление особенностей респираторных нарушений с помощью спирографии и бодиплетизмографии.Материалы и методы. Проведено клинико-функциональное исследование 57 лиц (10  здоровых (группа контроля), 30 больных с ХОБЛ и 17 больных, у которых РЛ сочетался  с ХОБЛ) при помощи диагностического комплекса Masterlab Pro (Erich Jaeger, Германия).Результаты. При начальной стадии ХОБЛ наиболее информативно снижение максимального объема скорости на уровне 75% от форсированной жизненной емкости легких (МОС75) – вентиляционного показателя, характеризующего проходимость мелких дыхательных путей. При прогрессировании бронхиальной обструкции отмечались как обструктивные, так и рестриктивные нарушения, характеризующиеся снижением объема форсированного выдоха за первую секунду, жизненной емкости легких, изменением структуры общей емкости легких в виде увеличения отношения остаточного объема легких к общей емкости легких и повышения бронхиального сопротивления. У пациентов, страдающих РЛ в сочетании с нетяжелой ХОБЛ, показатели вентиляции легких и бронхиальное сопротивление не отличались от пациентов с ХОБЛ, имеющих аналогичную степень бронхиальной обструкции. При РЛ в сочетании с более тяжелой ХОБЛ, в отличие от пациентов, страдающих аналогичной тяжестью ХОБЛ,  установлено снижение проходимости бронхов крупного, среднего и мелкого диаметра (пиковая  объемная скорость, МОС25, МОС50, МОС75), свидетельствующее о развитии генерализованной бронхиальной обструкции. Заключение. Современная диагностика нарушений вентиляции легких у больных РЛ в  сочетании с ХОБЛ должна быть направлена на выявление, а медикаментозная терапия – на максимальное нивелирование обратимых компонентов бронхиальной обструкции с целью повышения функционального резерва системы дыхания и снижения риска послеоперационных осложнений, вызванных ХОБЛ

Dual Role of p53 in Innate Antiviral Immunity

Tumor suppressor p53 is widely known as ‘the guardian of the genome’ due to its ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis. However, recent studies indicate that p53 is also a direct transcriptional target of type I interferons (IFNs) and thus, it is activated by these cytokines upon viral infection. p53 has been shown to contribute to virus-induced apoptosis, therefore dampening the ability of a wide range of viruses to replicate and spread. Interestingly, recent studies also indicate that several IFN-inducible genes such as interferon regulatory factor 9 (IRF9), IRF5, IFN-stimulated gene 15 (ISG15) and toll-like receptor 3 (TLR3) are in fact, p53 direct transcriptional targets. These findings indicate that p53 may play a key role in antiviral innate immunity by both inducing apoptosis in response to viral infection, and enforcing the type I IFN response, and provide a new insight into the evolutionary reasons why many viruses encode p53 antagonistic proteins

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

Background Microvascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE. Methods Patients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort. Results Forty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%. Conclusion Segmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ИНТРАОПЕРАЦИОННОЙ ЛУЧЕВОЙ ТЕРАПИИ ПРИ НЕМЕЛКОКЛЕТОЧНОМ РАКЕ ЛЕГКОГО

The purpose of the study was to analyze long-term outcomes of intraoperative radiation therapy (IORT) in patients with stage III non-small cell lung cancer (NS CLC).Material and Methods. The study included 103 patients with stage III NS CLC treated at the Cancer Research Institute (Tomsk, Russia). All patients were divided into two groups. Group I consisted of 51 patients, who underwent radical surgery and IORT at a single dose of 15 Gy. Group II (control group) comprised 52 patients, who underwent radical surgery alone. There were 34 (33 %) pneumonectomies, 39 (37.9 %) lob-, bilobectomies, 9 (8.7 %) reconstructive surgeries and 21 (20.4 %) combined surgeries. A compact pulsed betatron MIB-6E with the average electron energy of 6 MeV, located directly in the operating unit, was used for performing IORT. The Kaplan-Meier method was used for survival analysis. The significance of differences in survival between groups was assessed using the log rank test.Results. Excluding the cases lost to follow-up and deaths from concomitant non-malignant diseases, treatment outcomes were followed up in 97 of 103 patients with NS CLC for 3, 5, and 10 years. The 3-year and disease-free survival rates were significantly higher in the IORT group than in the control group (p<0.05). The IORT reduced the frequency of locoregional recurrence from 28.6 % to 20.8 % and increased recurrence-free survival from 12 to 17.1 months. In patients with stage III NS CLC, who received combined modality treatment including IORT, the 5and 10-year disease-free survival rates were 18.7 % and 12.5 %, respectively. In the control group patients, the corresponding values were 14.3 % and 6.1 %, respectively (р<0.05). The 5and 10-year overall survival rates were 29.2 % and 18.7 % versus 20.4 % and 8.2 %, respectively (р<0.05).Conclusion. In patients with stage III NS CLC, combined modality treatment, including radical surgery and IORT, results in a better local control and higher long-term survival rates compared to surgery alone.Цель исследования – изучить отдаленные результаты использования интраоперационной лучевой терапии (ИОЛТ) у больных немелкоклеточным раком легкого (НМРЛ) III стадии.Материал и методы. В исследование были включены 103 больных НМРЛ III стадии, которые проходили лечение в торако-абдоминальном отделении НИИ онкологии Томского НИМЦ. Больные были распределены на две группы: I группа (основная) – радикальная операция и ИОЛТ 15 Гр (51 больной); II группа (контрольная) – радикальная операция (52 больных). Хирургическое лечение в основной и контрольных группах было проведено в объеме: пневмонэктомии – 34 (33 %), лоб-, билобэктомии – 39 (37,9 %), реконструктивно-пластические операции – 9 (8,7 %) и комбинированные операции – 21 (20,4 %). В I группе после выполнения основного этапа оперативного вмешательства проводилась ИОЛТ в однократной дозе 15 Гр на пути регионарного лимфооттока. Для ИОЛТ в НИИ онкологии Томского НИМЦ применяется малогабаритный импульсный бетатрон МИБ-6Э со средней энергией электронов 6 МэВ, расположенный непосредственно в операционном блоке. Кривые выживаемости строились по методу Каплана – Майера. Значимость различий в выживаемости между группами оценивали при помощи «Log rank test».Результаты. С учетом выбывших из-под наблюдения и умерших от сопутствующих неонкологических заболеваний исходы лечения были прослежены у 97 из 103 больных НМРЛ в течение 3, 5 и 10 лет. Результаты лечения по показателю 3-летней безрецидивной и общей выживаемости были значимо (p<0,05) улучшены за счет использования высокой однократной дозы ИОЛТ, которая позволяет существенно снизить количество локорегионарных рецидивов – с 28,6 до 20,8 % и увеличить длительность безрецидивного периода с 12 до 17,1 мес. При комбинированном лечении с ИОЛТ безрецидивная 5и 10-летняя выживаемость больных НМРЛ III стадии составила 18,7 и 12,5 %, в группе контроля – 14,3 и 6,1 % (р<0,05), общая 5и 10-летняя выживаемость – 29,2 и 18,7 % против 20,4 и 8,2 % соответственно (р<0,05).Заключение. Комбинированное лечение, включающее радикальную операцию и ИОЛТ, обеспечивает надежный локальный контроль и позволяет значимо улучшить отдаленную выживаемость больных НМРЛ III стадии по сравнению с группой хирургического лечения