Correlated interaction fluctuations in photosynthetic complexes

The functioning and efficiency of natural photosynthetic complexes is strongly influenced by their embedding in a noisy protein environment, which can even serve to enhance the transport efficiency. Interactions with the environment induce fluctuations of the transition energies of and interactions between the chlorophyll molecules, and due to the fact that different fluctuations will partially be caused by the same environmental factors, correlations between the various fluctuations will occur. We argue that fluctuations of the interactions should in general not be neglected, as these have a considerable impact on population transfer rates, decoherence rates and the efficiency of photosynthetic complexes. Furthermore, while correlations between transition energy fluctuations have been studied, we provide the first quantitative study of the effect of correlations between interaction fluctuations and transition energy fluctuations, and of correlations between the various interaction fluctuations. It is shown that these additional correlations typically lead to changes in interchromophore transfer rates, population oscillations and can lead to a limited enhancement of the light harvesting efficiency

Healthy Ageing: prevention of loneliness among elderly people : evaluation of a complex intervention in public health practice

Introduction Concerns about the ageing population and formal responsibilities of local governments to promote social cohesion and to enhance participation of vulnerable groups in society placed loneliness prevention high on the local policy agenda of Dutch municipalities in the past decade. The study described in this thesis was part of the Healthy Ageing programme of the Academic Collaborative Centre AGORA and aimed to contribute to more effective, evidence-based and problem-oriented approaches to healthy ageing at the local level. Aim The general aim of this thesis was to evaluate the effectiveness of a local intervention project – called Healthy Ageing – targeting loneliness among non-institutionalised elderly people. Healthy Ageing consisted of five intervention components, namely, a mass media campaign, information meetings, psychosocial group courses, social activities organised by neighbours, Neighbours Connected, and training of intermediaries. Methods First, the influence of socio-demographic and health characteristics on changes in loneliness over time and municipal differences in the prevalence of loneliness were investigated. Data were gathered from 9,641 persons who participated in the Elderly Health Survey of the community health service, GGD Noord- en Oost- Gelderland (former GGD Gelre-IJssel), in 2005 or 2010. Second, the overall-effect of Healthy Ageing on the initial outcome loneliness literacy, intermediate outcome social support, and ultimate outcome loneliness was evaluated using a quasi-experimental pre-test post-test design, including an intervention and control community. Baseline and follow-up measurements, in 2008 and 2010 respectively, were available for 858 non-institutionalized elderly people. The Loneliness Literacy Scale was developed within the context of this thesis and was pre-tested in a separate study among 303 elderly persons who also participated in the quasi-experimental study. Finally, delivery, reach, and acceptance of the individual intervention components was studied in several satellite studies. Data were collected by different means, e.g. project records and surveys among participants. Furthermore, the acceptability of the mass media communication materials, information meetings, and psychosocial courses of Healthy Ageing was studied by in-depth interviews with 14 clients of the meal delivery service in the intervention community.   Results Overall and across municipalities, average loneliness scores did not significantly differ between 2005 and 2010. However, among the subgroup with mobility disabilities, loneliness was significantly higher in 2010. Furthermore, mobility disabilities and marital status were the most important factors explaining differences between municipalities. With regard to the evaluation of Healthy Ageing, the satellite studies showed that the reach and intensity of the intervention components were modest. Furthermore, from the interviews it appeared that the mass media communication materials were not successful in attracting attention because interviewees did not expect health information from these communication channels, the perceived personal relevance of the message was low, and the presentation was not attractive. Moreover, the content of the intervention components was not well received because the objectives and intervention components did not connect well with the priority group’s daily life. In addition, it appeared from the quasi-experimental study that 39% of the study participants from the intervention community was familiar with Healthy Ageing at follow-up. Overall, the intervention group scored more favourably on the loneliness literacy subscales, motivation (4.4%), perceived social support (8.2%), and subjective norm (11.5%) than the control group. However, no overall effects were observed for the intermediate and ultimate outcomes, total social support and loneliness after two years. Conclusion Given the modest overall intervention exposure, the effect of Healthy Ageing on the loneliness literacy subscale, motivation, is plausible, whereas on the subscales, perceived social support and subjective norm, probable, and on the subscale, self-efficacy, unlikely. Furthermore, whether the initial effects will carry forward to the intermediate and ultimate outcomes needs to be confirmed. The modest effects of Healthy Ageing can partly be explained by the challenges on organisational level which delayed and suppressed project implementation. Furthermore, the project might have benefited from a more systematic approach in order to ensure better alignment between the intervention components and formulated objectives. Finally, target group differentiation is highly recommended. This evaluation of Healthy Ageing illustrates how researchers can cope with the evaluation challenges of complex interventions which cannot be fully controlled. In turn, this provides valuable lessons for the development of intervention programmes and evaluation designs in public health practice.</p

Повышение работоспособности торцовых фрез с механическим креплением режущих пластин

Объектом исследования является торцовые фрезы с механическим крепление режущих пластин. Цель работы – подтверждение квалификации "магистр техники и технологии" по направлению 15.04.01 "Автоматизация технологических процессов и производств в машиностроении". В процессе исследования проводились обзор и анализ научно-технической литературы по теме магистерской работы, формулирование цели и задач исследования. В работе представлены результаты экспериментального исследования влияние толщины среза и переднего угла на технологические и физические составляющие силы резания при использовании сменных многогранных пластин (СМП), которые будут использованы на торцовых фрезах.The object of research is face mills with mechanical fastening of cutting plates. The purpose of the work is to confirm the qualification "Master of engineering and technology" in the major 15.04.01 "Automation of technological processes and productions in mechanical engineering". During the research, the review and analysis of scientific and technical literature on the topic of master's work, the formulation of the goals and objectives of the research were carried out. The paper presents the results of an experimental study of the effect of the uncut thickness and the rake angle on the technological and physical components of the cutting force when using replaceable polyhedral plates (RPP), which will be used on face mills

The Novel Immune Checkpoint GPR56 Is Expressed on Tumor-Infiltrating Lymphocytes and Selectively Upregulated upon TCR Signaling

High levels of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) are associated with a survival benefit in various cancer types and the targeted (re)activation of TILs is an attractive therapeutic anti-cancer approach that yields curative responses. However, current T cell targeting strategies directed at known immune checkpoints have not increased objective response rates for all cancer types, including for epithelial ovarian cancer (EOC). For this reason, the identification of new immune checkpoints that regulate T cell immunity remains of great interest. One yet largely uninvestigated checkpoint of potential interest is the G protein-coupled receptor 56 (GPR56), which belongs to the adhesion GPCR family. GPR56 was originally reported to function in cerebral cortical development and in anti-depressant response, but also in cancer. Recently, GPR56 was identified as an inhibitory receptor expressed on human NK cells that by cis-interaction with the tetraspanin CD81 attenuated the cytotoxic activity of NK cells. This NK cell checkpoint could be blocked by an GPR56 antibody, leading to increased cytotoxicity. Interestingly, GPR56 expression has also been reported on cytokine producing memory CD8 T lymphocytes and may thus represent a T cell checkpoint as well. Here, GPR56 mRNA expression was characterized in the context of TILs, with GPR56 expression being detected predominantly in tumor infiltrating CD8 T cells with a cytotoxic and (pre-)exhausted phenotype. In accordance with this mRNA profile, TILs from ovarian cancer patients expressed GPR56 primarily within the effector memory and central memory T cell subsets. On T cells from healthy donors the expression was limited to effector memory and terminally differentiated T cells. Notably, GPR56 expression further increased on TILs upon T cell receptor (TCR)-mediated stimulation in co-cultures with cancer cells, whereas GPR56 expression on healthy primary human T cells did not. Further, the ectopic expression of GPR56 significantly reduced the migration of GPR56-positive T cells. Taken together, GPR56 is a potential immune-checkpoint in EOC found on (pre-)exhausted CD8 TILs that may regulate migratory behavior

Формирование портфеля ценных бумаг на основе котировок европейского рынка акций и программной среды R

В данной работе проводится анализ котировок акций в европейских странах, определяется эффективность инвестирования в ценные бумаги определенной страны. По полученной выборке формируется портфель акций с базовой валютой евро. Для оценки эффективности портфеля рассчитываются рисковые коэффициенты, сравнивается динамика сформированного портфеля ценных бумаг с динамикой мирового индекса. Практическая реализация осуществляется в программной среде R.In this paper we analyze stock quotes in European countries and determine the effectiveness of investing in securities of a particular country. A portfolio of shares with the base currency of the Euro is formed based on the received sample. To assess the effectiveness of the portfolio, risk coefficients are calculated, the dynamics of the formed securities portfolio is compared with the dynamics of the world index. Practical implementation is carried out in the software environment R

Magnetic Correlations in the Two Dimensional Anderson-Hubbard Model

The two dimensional Hubbard model in the presence of diagonal and off-diagonal disorder is studied at half filling with a finite temperature quantum Monte Carlo method. Magnetic correlations as well as the electronic compressibility are calculated to determine the behavior of local magnetic moments, the stability of antiferromagnetic long range order (AFLRO), and properties of the disordered phase. The existence of random potentials (diagonal or ``site'' disorder) leads to a suppression of local magnetic moments which eventually destroys AFLRO. Randomness in the hopping elements (off-diagonal disorder), on the other hand, does not significantly reduce the density of local magnetic moments. For this type of disorder, at half-filling, there is no ``sign-problem'' in the simulations as long as the hopping is restricted between neighbor sites on a bipartite lattice. This allows the study of sufficiently large lattices and low temperatures to perform a finite-size scaling analysis. For off-diagonal disorder AFLRO is eventually destroyed when the fluctuations of antiferromagnetic exchange couplings exceed a critical value. The disordered phase close to the transition appears to be incompressible and shows an increase of the uniform susceptibility at low temperatures.Comment: 10 pages, REVTeX, 14 figures included using psfig.st

Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior.

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets

EGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells

A higher density of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment, particularly cytotoxic CD8 + T cells, is associated with improved clinical outcome in various cancers. However, local inhibitory factors can suppress T cell activity and hinder anti-tumor immunity. Notably, TILs from various cancer types express the co-stimulatory Tumor Necrosis Factor receptor CD27, making it a potential target for co-stimulation and re-activation of tumor-infiltrated and tumor-reactive T cells. Anti-cancer therapeutics based on exploiting CD27-mediated T cell co-stimulation have proven safe, but clinical responses remain limited. This is likely because current monoclonal antibodies fail to effectively activate CD27 signaling, as this receptor requires higher-order receptor cross-linking. Here, we report on a bispecific antibody, CD27xEGFR, that targets both CD27 and the tumor antigen, epidermal growth factor receptor (EGFR). By targeting EGFR, which is commonly expressed on carcinomas, CD27xEGFR induced cancer cell-localized crosslinking and activation of CD27. The design of CD27xEGFR includes an Fc-silent domain, which is designed to minimize potential toxicity by reducing Fc gamma receptor-mediated binding and activation of immune cells. CD27xEGFR bound to both of its targets simultaneously and triggered EGFR-restricted co-stimulation of T cells as measured by T cell proliferation, T cell activation markers, cytotoxicity and IFN-γ release. Further, CD27xEGFR augmented T cell cytotoxicity in a panel of artificial antigen-presenting carcinoma cell line models, leading to Effector-to-Target ratio-dependent elimination of cancer cells. Taken together, we present the in vitro characterization of a novel bispecific antibody that re-activates T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27. </p

Mott-Hubbard Transition and Anderson Localization: Generalized Dynamical Mean-Field Theory Approach

Density of states, dynamic (optical) conductivity and phase diagram of strongly correlated and strongly disordered paramagnetic Anderson-Hubbard model are analyzed within the generalized dynamical mean field theory (DMFT+\Sigma approximation). Strong correlations are accounted by DMFT, while disorder is taken into account via the appropriate generalization of self-consistent theory of localization. The DMFT effective single impurity problem is solved by numerical renormalization group (NRG) and we consider the three-dimensional system with semi-elliptic density of states. Correlated metal, Mott insulator and correlated Anderson insulator phases are identified via the evolution of density of states and dynamic conductivity, demonstrating both Mott-Hubbard and Anderson metal-insulator transition and allowing the construction of complete zero-temperature phase diagram of Anderson-Hubbard model. Rather unusual is the possibility of disorder induced Mott insulator to metal transition.Comment: 15 pages, 16 figure