Membrane heterogeneity : from lipid domains to curvature effects

Membrane heterogeneity on the micro- and nanometer scale plays an important role for a large number of biological processes. In parallel to the conception of refined membrane models, new experimental techniques to determine membrane microstructure were developed in recent years. Single molecule fluorescence has emerged as one of the leading technologies since it delivers the required spatial resolution and can be employed in living cells. In a complementary approach artificial model systems are used to study specific biophysical aspects of membranes in isolation and in a controllable way. In this thesis we show how phase separated artificial membranes can be used to gain fundamental insight into lipid composition based heterogeneity (Chap. 2) and membrane mediated interactions (Chap. 3). We demonstrate that those interactions can lead to lipid domain sorting (Chap. 4). Experiments with artificial membranes are complemented with live cell studies. We develop a robust analysis method for single molecule position data (Chap. 5) and use it to study the role of heterogeneity in cell signaling (Chap. 6). Finally, we show how protein cluster formation can be measured by counting single molecules in live cells (Chap. 7).LEI Universiteit LeidenStichting voor Fundamenteel Onderzoek der Materie (FOM), die financieel wordt gesteund door de Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).Biological and Soft Matter Physic

Why isn't each cell its own cell type?

Biological and Soft Matter Physic

How a cell decides its own fate: a single-cell view of molecular mechanisms and dynamics of cell-type specification

Biological and Soft Matter Physic

Service user involvement in global mental health: what have we learned from recent research in low- and middle-income countries?

Purpose of Review The Lancet Commission on global mental health and sustainable development claims the field of global mental health is undergoing a “transformational shift” toward an ethic of “nothing about us without us”. Yet a systematic review published in 2016 identified few examples of meaningful participation by service users in mental health systems strengthening in low- and middle-income countries (LMICs). To investigate whether this is still the case, we conducted a rapid review of primary research published between June 2017 and December 2018. Recent Findings We identified 10 studies reporting on user involvement in LMICs, including three in mental health policy and planning, three in mental health services or capacity-building, and three in treatment decision-making. An additional study was identified as having involved users in data collection, although this was unclear from the original text. Included studies were mostly qualitative and conducted as part of a situation analysis, pilot study or other formative research. Few reported the results of efforts to improve involvement, suggesting this shift remains at an early stage. Summary While the number of studies published on user involvement is rapidly increasing, the potentially “transformational” effects of this shift in global mental health are not yet being felt by most users in LMICs

A Qualitative Study of Georgian Youth Who Are on the Street or Institutionalized

Street children, or children who live and/or spend time on the streets, are a vulnerable group of considerable concern to the global public health community. This paper describes the results of two linked qualitative studies conducted with children living or spending time on the street and in orphanages in and around urban areas in the Republic of Georgia between 2005 and 2006. The studies examined perceived causes of children going to the street, as well as indicators of healthy functioning and psychosocial problems among these children. Results on causes indicated a range of “push” factors leading children to the street and “pull” factors that keep children living on the street. Findings also showed a range of internalizing and externalizing mental health symptoms among children on the street and within orphanages. Some differences in responses were found between children living on the street and in institutions. It is important to understand the perspectives of these vulnerable populations to guide decisions on appropriate interventions that address their primary problems

Designable electron transport features in one-dimensional arrays of metallic nanoparticles: Monte Carlo study of the relation between shape and transport

We study the current and shot noise in a linear array of metallic nanoparticles taking explicitly into consideration their discrete electronic spectra. Phonon assisted tunneling and dissipative effects on single nanoparticles are incorporated as well. The capacitance matrix which determines the classical Coulomb interaction within the capacitance model is calculated numerically from a realistic geometry. A Monte Carlo algorithm which self-adapts to the size of the system allows us to simulate the single-electron transport properties within a semiclassical framework. We present several effects that are related to the geometry and the one-electron level spacing like e.g. a negative differential conductance (NDC) effect. Consequently these effects are designable by the choice of the size and arrangement of the nanoparticles.Comment: 13 pages, 12 figure

Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): A feasibility study

Background: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. Patients and Methods: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m(2)). This was to be followed by 2 cycles of cisplatin/vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. Results: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. Conclusion: Oral vinorelbine 50 mg/m(2) (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy

Capacity Benefits of Operation Over C+L Band Elastic Optical Network in the Indian Network Scenario

Introduction of high data rate services has increased the traffic load on the backhaul network. In order to cater more demands, the operators are looking for solutions to minimize spectral wastage and to extend their network operations beyond the C-band, especially for inter-city networks. This paper highlights the advantages of operating over C+L band as compared to operations over C band in a large Indian network. The physical model factors in the non-linear interference (NLI) due to inter-channel stimulated Raman scattering (ISRS) and amplified spontaneous emission (ASE) noise while estimating the optical signal to noise ratio (OSNR) of a network lightpath. The OSNR estimation model can dynamically account for the NLI as compared to the conventional worst case assumption. The capacity benefits for the Indian network over the C+L band for channel power -1.5 dBm are about 108.67% for channel bandwidth 50 GHz and 103.98% for channel bandwidth 37.5 GHz until 10% of the demands are blocked

Transformation of ortho-substituted biphenyls by Methylosinus trichosporium OB3b: substituent effects on oxidation kinetics and product formation

The ability of Methylosinus trichosporium OB3b, expressing soluble methane monooxygenase, to oxidize a range of ortho- substituted biphenyls was examined to better understand how substituents affect both the rate and products of oxidation in comparison to biphenyl. Inhibition of oxidation was observed over the tested substrate range for both biphenyl and ortho- halogenated biphenyls (2-chloro-, 2-bromo-, and 2-iodobiphenyl). No inhibition was observed during the oxidation of 2-hydroxybiphenyl and 2-methylbiphenyl. Analysis of the products of oxidation showed that, depending on the substituent, ring hydroxylation, substituent oxidation, and elimination pathways could occur. The type and abundance of products formed along with the relatively high kinetic isotope effect observed for deuterated vs. nondeuterated biphenyl ( k h / k d = 3.4±0.02) are consistent with mechanisms that include both hydrogen abstraction and NIH-shift pathways. Knowledge of these substituent-dependent reaction rates and mechanisms enhances our understanding of the methanotrophic aryl transformation potential and allows for better prediction of the formation of oxidized intermediates by methanotrophic bacteria.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41919/1/203-174-1-2-35_s002030000170.pd

Service user and caregiver involvement in mental health system strengthening in low- and middle-income countries: a cross-country qualitative study

The aims of this paper are to: (i) explore the experiences of involvement of mental health service users, their caregivers, mental health centre heads and policy makers in mental health system strengthening in three low- and middle-income countries (LMICs) (Ethiopia, Nepal and Nigeria); (ii) analyse the potential benefits and barriers of such involvement; and (iii) identify strategies required to achieve greater service user and caregiver participation. A cross-country qualitative study was conducted, interviewing 83 stakeholders of mental health services. Our analysis showed that service user and caregiver involvement in the health system strengthening process was an alien concept for most participants. They reported very limited access to direct participation. Stigma and poverty were described as the main barriers for involvement. Several strategies were identified by participants to overcome existing hurdles to facilitate service user and caregiver involvement in the mental health system strengthening process, such as support to access treatment, mental health promotion and empowerment of service users. This study suggests that capacity building for service users, and strengthening of user groups would equip them to contribute meaningfully to policy development from informed perspectives. Involvement of service users and their caregivers in mental health decision-making is still in its infancy in LMICs. Effective strategies are required to overcome existing barriers, for example making funding more widely available for Ph.D. studies in participatory research with service users and caregivers to develop, implement and evaluate approaches to involvement that are locally and culturally acceptable in LMICs