A very compact InP-based integrated optic Mach-Zehnder interferometer with a delay difference of 74 ps

A Mach-Zehnder interferometer with 6.0 mm arm length difference was realised on InP. The design is very compact, using deeply etched waveguides and circular bends with 50 mu m radius. The devices show a sinusoidal frequency response with 13.5 GHz period and extinction ratios up to 20 d

Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Background. Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses

MCF-SMF Hybrid Low-Latency Circuit-Switched Optical Network for Disaggregated Data Centers

This paper proposes and experimentally evaluates a fully developed novel architecture with purpose built low latency communication protocols for next generation disaggregated data centers (DDCs). In order to accommodate for capacity and latency needs of disaggregated IT elements (i.e. CPU, memory), this architecture makes use of a low latency and high capacity circuit switched optical network for interconnecting various endpoints, that are equipped with multi-channel Silicon photonic based integrated transceivers. In a move to further decrease the perceived latency between various disaggregated IT elements, this paper proposes a) a novel network topology, which cuts down the latency over the optical network by 34% while enhancing system scalability and b) channel bonding over multicore fiber (MCF) switched links to reduce head to tail latency and in turn increase sustained memory bandwidth for disaggregated remote memory. Furthermore, to reduce power consumption and enhance space efficiency, the integration of novel multi core fiber (MCF) based transceivers, fibers and optical switches are proposed and experimentally validated at the physical layer for this topology. It is shown that the integration of MCF based subsystems in this topology can bring about an improvement in energy efficiency of the optical switching layer which is above 60%. Finally, the performance of this proposed architecture and topology is evaluated experimentally at the application layer where the perceived memory throughput for accessing remote and local resources is measured and compared using electrical circuit and packet switching. The results also highlight a multi fold increase in application perceived memory throughput over the proposed DDC topology by utilization and bonding of multiple optical channels to interconnect disaggregated IT elements that can be carried over MCF links

Hygienic characteristics of radishes grown in soil contaminated with Stenotrophomonas maltophilia

Background: Stenotrophomonas maltophilia is a plant growth-promoter. This bacterium is also implicated in human diseases. Thus, after the use of this bacterium in agriculture, the safety of the final products has to be verified. Due to the ubiquitous presence of S. maltophilia in soil, in this study a massive contamination was simulated to evaluate the growth and safety of Raphanus sativus L.. Results: Different inoculums and soil treatment conditions were tested. Soils were analysed weekly and the radishes at harvest for their microbial loads and presence/persistence of S. maltophilia LMG 6606. The concentration of the bacterium added in the different trials decreased during the first week, but increased thereafter and determined a significant increase of growth parameters of radishes. Conclusions: The addition of S. maltophilia LMG 6606 to non-autoclaved soil enhanced the productivity of radishes. The bacterium did not internalize in the hypocotyls, but colonized the external surface ensuring the safety of the products. Thus, a sanitizing bath of hypocotyls before consumption is necessary

The Rts1 Regulatory Subunit of Protein Phosphatase 2A Is Required for Control of G1 Cyclin Transcription and Nutrient Modulation of Cell Size

The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclin-dependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell size does not work through known critical regulators of G1 cyclin transcription and is therefore thought to work through a distinct pathway. Here, we report that Rts1, a highly conserved regulatory subunit of protein phosphatase 2A (PP2A), is required for normal control of G1 cyclin transcription. Loss of Rts1 caused delayed initiation of bud growth and delayed and reduced accumulation of G1 cyclins. Expression of the G1 cyclin CLN2 from an inducible promoter rescued the delayed bud growth in rts1Δ cells, indicating that Rts1 acts at the level of transcription. Moreover, loss of Rts1 caused altered regulation of Swi6, a key component of the SBF transcription factor that controls G1 cyclin transcription. Epistasis analysis revealed that Rts1 does not work solely through several known critical upstream regulators of G1 cyclin transcription. Cells lacking Rts1 failed to undergo nutrient modulation of cell size. Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates

The impact of family structure and disruption on intergenerational emotional exchange in Eastern Europe

Demographic trends across Europe involve a decrease in fertility and mortality rates, and an increase in divorce and stepfamily formation. Life courses and living arrangements have become less standardized and the structure of families has changed. In this article, we examine to what extent contemporary family structure and composition resulting from demographic changes affect emotional exchange between children and their parents, both from adult child to parent and from parent to child. Because the general level of well-being has been shown to be lower in Eastern Europe, thereby potentially affecting emotional exchange within families, we focus our research on Eastern Europe. We use the “conservation of resources theory” to derive hypotheses on how family structure may affect intergenerational emotional exchange. Family ties are assumed to be important resources of affection that people want to obtain and retain throughout their lives. Data from the Generations and Gender Survey (GGS) are used to test our hypotheses. In general, our data offer more support for the idea that families are resilient than for the often heard assumption that families are in decline as a consequence of the changed family structure and composition

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders?A successful strategy for clinical research of rare diseases

BACKGROUND: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. AIMS: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. METHODS: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. RESULTS: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (</= 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. CONCLUSIONS: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies

Research activity and capability in the European reference network MetabERN

BACKGROUND: MetabERN is one of the 24 European Reference Networks created according to the European Union directive 2011/24/EU on patient's rights in cross border healthcare. MetabERN associates 69 centres in 18 countries, which provide care for patients with Hereditary Metabolic Diseases, and have the mission to reinforce research and provide training for health professionals in this field. MetabERN performed a survey in December 2017 with the aim to produce an overview documenting research activities and potentials within the network. As the centres are multidisciplinary, separated questionnaires were sent to the clinical, university and laboratory teams. Answers were received from 52 out of the 69 centres of the network, covering 16 countries. A descriptive analysis of the information collected is presented. RESULTS: The answers indicate a marked interest of the respondents for research, who expressed high motivation and commitment, and estimated that the conditions to do research in their institution were mostly satisfactory. They are active in research, which according to several indicators, is competitive and satisfies standards of excellence, as well as the education programs offered in the respondent's universities. Research in the centres is primarily performed in genetics, pathophysiology, and epidemiology, and focuses on issues related to diagnosis. Few respondents declared having activity in human and social sciences, including research on patient's quality of life, patient's awareness, or methods for social support. Infrastructures offering services for medical research were rarely known and used by respondents, including national and international biobanking platforms. In contrast, respondents often participate to patient registries, even beyond their specific field of interest. CONCLUSIONS: Taken as a whole, these results provide an encouraging picture of the research capacities and activities in the MetabERN network, which, with respect to the number and representativeness of the investigated centres, gives a comprehensive picture of research on Hereditary Metabolic Diseases in Europe, as well as the priorities for future actions. Marginal activity in human and social sciences points out the limited multidisciplinary constitution of the responding teams with possible consequences on their current capability to participate to patient's empowerment programs and efficiently collaborate with patient's advocacy groups