Quantization of the Riemann Zeta-Function and Cosmology

Quantization of the Riemann zeta-function is proposed. We treat the Riemann zeta-function as a symbol of a pseudodifferential operator and study the corresponding classical and quantum field theories. This approach is motivated by the theory of p-adic strings and by recent works on stringy cosmological models. We show that the Lagrangian for the zeta-function field is equivalent to the sum of the Klein-Gordon Lagrangians with masses defined by the zeros of the Riemann zeta-function. Quantization of the mathematics of Fermat-Wiles and the Langlands program is indicated. The Beilinson conjectures on the values of L-functions of motives are interpreted as dealing with the cosmological constant problem. Possible cosmological applications of the zeta-function field theory are discussed.Comment: 14 pages, corrected typos, references and comments adde

Enhanced inverse bremsstrahlung heating rates in a strong laser field

Test particle studies of electron scattering on ions, in an oscillatory electromagnetic field have shown that standard theoretical assumptions of small angle collisions and phase independent orbits are incorrect for electron trajectories with drift velocities smaller than quiver velocity amplitude. This leads to significant enhancement of the electron energy gain and the inverse bremsstrahlung heating rate in strong laser fields. Nonlinear processes such as Coulomb focusing and correlated collisions of electrons being brought back to the same ion by the oscillatory field are responsible for large angle, head-on scattering processes. The statistical importance of these trajectories has been examined for mono-energetic beam-like, Maxwellian and highly anisotropic electron distribution functions. A new scaling of the inverse bremsstrahlung heating rate with drift velocity and laser intensity is discussed.Comment: 12 pages, 12 figure

Altered DNA methylation associated with a translocation linked to major mental illness

Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA). We found significant differences in DNA methylation when translocation carriers (n = 17) were compared to related non-carriers (n = 24) at 13 loci. All but one of the 13 significant differentially methylated positions (DMPs) mapped to the regions surrounding the translocation breakpoints. Methylation levels of five DMPs were associated with genotype at SNPs in linkage disequilibrium with the translocation. Two of the five genes harbouring significant DMPs, DISC1 and DUSP10, have been previously shown to be differentially methylated in schizophrenia. Gene Ontology analysis revealed enrichment for terms relating to neuronal function and neurodevelopment among the genes harbouring the most significant DMPs. Differentially methylated region (DMR) analysis highlighted a number of genes from the MHC region, which has been implicated in psychiatric illness previously through genetic studies. We show that inheritance of a translocation linked to major mental illness is associated with differential DNA methylation at loci implicated in neuronal development/function and in psychiatric illness. As genomic rearrangements are over-represented in individuals with psychiatric illness, such analyses may be valuable more widely in the study of these conditions

ПОСЛЕОПЕРАЦИОННЫЕ ОСЛОЖНЕНИЯ МАЛОИНВАЗИВНЫХ МЕТОДОВ ЛЕЧЕНИЯ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ

Prostate cancer is the most common cancer among men. Radical prostatectomy (open, laparoscopic, or robotic) remains the main method of surgical treatment for prostate cancer. However, minimally invasive therapies for prostate cancer are becoming increasingly popular in recent years, because they have similar efficacy as open surgery. The most studied minimally invasive therapies are cryoablation, high intensity focused ultrasound (HIFU), and brachytherapy.Despite the minimization of damage to neighboring structures, minimally invasive procedures can cause a number of complications, like any other surgical interventions. Each method has specific limitations and the most typical complications. Since multiple minimally invasive methods are currently available, we can ensure an individual approach to each particular patient, thus using the advantages of the methods and avoiding possible complications. This article covers the most frequent and severe complications of minimally invasive therapies for prostate cancer, as well as the methods of their prevention and treatment.Рак предстательной железы (РПЖ) является наиболее распространенным онкологическим заболеванием среди мужчин. Радикальная простатэктомия (открытая, лапароскопическая, роботическая) считается основным хирургическим методом лечения РПЖ. Однако в последние годы все бόльшую популярность набирают малоинвазивные методы лечения РПЖ, которые не отстают по эффективности от радикальной операции (по данным последних исследований). К наиболее изученным малоинвазивным технологиям относятся криоаблация, HIFU-терапия (High Intensity Focused Ultrasound) и брахитерапия.Несмотря на минимизацию повреждения соседних структур, малоинвазивные методы лечения РПЖ, как и любые другие хирургические вмешательства, могут приводить к развитию ряда осложнений. Для каждого из методов существуют определенные ограничения, а также наиболее характерные и вероятные осложнения. Благодаря существованию на сегодняшний день целого ряда малоинвазивных методов лечения РПЖ возможен индивидуальный подход к конкретному пациенту, что позволяет избежать нежелательных осложнений и использовать сильные стороны каждого из методов. В настоящей работе рассмотрены наиболее частые и тяжелые осложнения, возникающие после малоинвазивного лечения РПЖ, а также методы их профилактики и лечения

Возможность использования местной анестезии при чрескожной криоаблации почечно - клеточного рака под ультразвуковым контролем

Background. There is a category of patients with renal masses, due to severe concomitant diseases, can not perform the operation or may be associated with a threat to life. In addition, many patients with small tumor sites are extremely concerned about their disease and are negative about the tactics of active observation and insist on treatment. These patients can be offered alternative methods of treatment of renal cell carcinoma (RCC), the leading of which is cryoablation.Objective: to evaluate the effectiveness and safety of percutaneous cryoablation of the kidney tumor under ultrasound control.Materials and methods. In the Urology Clinic of the I.M. Sechenov First Moscow State Medical University during the period from 2015 to 2017 performed 23 percutaneous cryoablation of RCC, 7 (men – 4, women – 3) of which were performed under local anesthesia. In 4 patients due to severe concomitant diseases, general anesthesia was associated with an extremely high risk. Three patients refused from dynamic observation and from traditional surgical treatment; preferred an alternative treatment in the form of a percutaneous cryoablation under local anesthesia. In 4 cases, the formations were located in the lower segment along the posterior surface of the kidney, in 3 – along the lateral surface in the middle segment. The size of the formations was not used 4 cm (T1a). The age of the patients was 62.3 years (51 to 83 years). Right-sided localization of the tumor was noted in 3 patients, left-sided – in 4. One patient had a single kidney.At the preoperative stage and 6 months after the operation, all patients underwent ultrasound with dopplerography, multislice computerized tomography with contrast, and computer 3D modeling, which helped to clearly assess the size of the tumor, clarify the prevalence of the tumor process and the spatial ratio of the internal surface of the tumor node to the elements of the bowl-and-pelvis system. In all the observations, the formations were located along the posterior or lateral surface of the kidney; in the lower or middle segment; without invasion of the sine. We used a 3rd generation cryomash machine SeedNet gold (Galil Medical), cryoprobes IceSeed and IceRod. Intraoperative, immediately before cryoablation, a tumor biopsy was performed, the presence of RCC in all patients was confirmed morphologically.Results. According to the ultrasound examination with echodopplerography at 6 months after the operation, the size of the tumor node’s formations decreased on average by 6–8 mm, while there was no blood flow in them. When multislice computerized tomography with 3D modeling was performed, the formation was reduced and the accumulation of the contrast preparation was completely absent or their accumulation gradient did not exceed 10 HU (initially it was about 200 HU). There were no intraoperative complications. In 1 observation, a postoperative hematoma measuring 7 × 3 cm was resolved conservatively and did not require surgical treatment.Conclusions. Percutaneous cryodestruction under local anesthesia using ultrasound guidance seems to be an effective and safe technique for treating patients with stage T1a RCC with localization in the posterior or lateral surface in the lower or middle segments without invasion of the renal sinus and surrounding tissues. It is planned to continue monitoring patients to assess the long-term effectiveness of cryoablation.Введение. Существует категория пациентов c почечно-клеточным раком (ПКР), у которых в связи с тяжелыми сопутствующими заболеваниями операция не может быть выполнена или сопряжена с угрозой для жизни. Кроме того, многие пациенты с небольшим размером опухолевого узла крайне обеспокоены своим заболеванием и отрицательно относятся к тактике активного наблюдения, настаивая на лечении. Таким пациентам могут быть предложены альтернативные методы терапии ПКР, ведущим из которых является криоаблация.Цель исследования – оценить эффективность и безопасность чрескожной криоаблации опухоли почки под ультразвуковым контролем. Материалы и методы. В клинике урологии Первого Московского государственного медицинского университета им. И.М. Сеченова в период с 2015 по 2017 г. выполнены 23 чрескожные криоаблации ПКР, из них 7 (4 мужчин, 3 женщин) проводили под местной анестезией. У 4 пациентов ввиду тяжелых сопутствующих заболеваний общее обезболивание было сопряжено с крайне высоким риском. От динамического наблюдения и традиционного хирургического лечения отказались 3 пациента. Они предпочли альтернативное лечение в виде чрескожной криоаблации под местной анестезией. В 4 наблюдениях образования располагались в нижнем сегменте по задней поверхности почки, в 3 – в среднем сегменте по латеральной поверхности. Размер образований не превышал 4 см (стадия Т1a). Средний возраст пациентов составил 62,3 года (51–83 года). Правосторонняя локализация опухоли отмечена у 3 пациентов, левосторонняя – у 4. У 1 больного почка была единственной.На дооперационном этапе и через 6 мес после вмешательства всем пациентам проведены ультразвуковое исследование с допплерографией, мультиспиральная компьютерная томография с контрастированием и компьютерное трехмерное моделирование, что помогало четко оценить размер опухоли, уточнить распространенность опухолевого процесса и пространственное отношение внутренней поверхности опухолевого узла к элементам чашечно-лоханочной системы. Во всех наблюдениях образования располагались по задней или латеральной поверхности почки в нижнем или среднем сегменте без инвазии в синус.Мы использовали криомашину 3-го поколения SeedNet gold (Galil Medical), криозонды IceSeed и IceRod. За 3 нед до проведения операции выполняли биопсию опухоли. Наличие ПКР у всех больных было подтверждено морфологически.Результаты. По данным ультразвукового обследования с эходопплерографией через 6 мес после операции размер образований опухолевого узла уменьшился в среднем на 6–8 мм, при этом в них отсутствовал кровоток. При проведении мультиспиральной компьютерной томографии с трехмерным моделированием также отмечались уменьшение образований и полное отсутствие накопления контрастного препарата либо его градиент накопления не превышал 10 ед. HU (первоначально он составлял около 200 ед. HU). Интраоперационных осложнений не зарегистрировано. В 1 наблюдении выявлена послеоперационная гематома размером 7 × 3 см, разрешившаяся консервативно и не потребовавшая оперативного лечения.Заключение. Чрескожная криодеструкция под местной анестезией с использованием ультразвуковой навигации представляется эффективной и безопасной методикой лечения больных ПКР стадии Т1а с локализацией образования по задней или латеральной поверхности в нижнем или среднем сегменте без инвазии в почечный синус и окружающие ткани. Планируется продолжить наблюдение за пациентами для оценки долгосрочной эффективности криоаблации

Modes of Aβ toxicity in Alzheimer’s disease

Alzheimer’s disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide

Modal identification of a boundary input in the two-dimensional inverse heat conduction problem

A method for the approximate solution of a two-dimensional inverse boundary heat conduction problem on a compact set of continuous and continuously differentiable functions is proposed. The method allows us to reconstruct a boundary action that depends on time and a spatial coordinate. A modal description of the object is used in the form of an infinite system of linear differential equations with respect to the coefficients of the expansion of the state function in a series in eigenfunctions of the initial-boundary value problem under study. This approach leads to the restoration of the sought value of the heat flux density in the form of a weighted sum of a finite number of its modal components. Their values are determined from the temporal modes of the temperature field, which are found from the experimental data on the basis of the modal representation of the field. To obtain a modal description of the identified input and the temperature field in the form of their expansions into series in eigenfunctions of the same spatial dimension, the mathematical model of the object in the Laplace transform domain and the method of finite integral transformations are used. On this basis, a closed system of equations with respect to the unknown quantities is formed. The proposed approach allows us to construct a sequence of approximations that uniformly converge to the desired solution with increasing number of considered modal components. The problem of the temperature experimental design is solved. This solution ensures the minimization of the approximation error of the experimental temperature field by its model representation in the uniform metric of estimating temperature discrepancies on the control line at the final moment of the identification interva