Ovarian reserve and anti-Mullerian hormone (AMH) in mothers of dizygotic twins

This study aimed to explore if natural dizygotic (DZ) twinning is associated with earlier menopause and lower anti-Mullerian hormone (AMH) values. We investigated if advanced biological reproductive aging, which can be responsible for the multiple follicle growth in familial twinning, is similar to mechanisms that occur in normal ovarian aging, reflected by earlier menopause in mothers of DZ twins and lower levels of AMH. A total of 16 mothers of DZ twins enrolled with the Netherlands Twin Register (average age at first assessment: 35.9 +/- 3.0 years) and 14 control mothers (35.1 +/- 3 years) took part in a prospective study. Fifteen years after entry into the study, which included follicle-stimulating hormone (FSH) assessment, AMH was measured in stored serum samples and menopause status was evaluated. Average AMH levels were not significantly different between DZ twin mothers and controls (2.1 +/- 2.4 mu g/L vs. 1.9 +/- 1.9 mu g/L). Among the 16 mothers of twins, 7 had an elevated (FSH) value over 10 U/L at first assessment. Their AMH levels were lower than the nine twin mothers with normal FSH values: 0.6 +/- 0.4 versus 3.4 +/- 2.6 mu g/L (p = .01). Of the mothers of twins, eight mothers had entered menopause at the second assessment compared with only one control mother (p = .07). Thus, slightly more DZ mothers were in menopause than the control mothers, although this difference was not significant. The subgroup of DZ twin mothers who had an increased FSH concentration 15 years ago had a limited ovarian reserve as reflected by lower AMH levels. These data indicate that advanced ovarian aging can be a feature in familial DZ twinning, particularly with elevated early follicular phase FSH

Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico

Malaria is one of the world’s most common and serious diseases causing death of about 3 million people each year. Its most severe occurrence is caused by the protozoan Plasmodium falciparum. Biomedical research could enable treating the disease by effectively and specifically targeting essential enzymes of this parasite. However, the parasite has developed resistance to existing drugsmaking it indispensable to discover new drugs. We have established a simple computational tool which analyses the topology of the metabolic network of P. falciparum to identify essential enzymes as possible drug targets.Weinvestigated the essentiality of a reaction in the metabolic network by deleting (knocking-out) such a reaction in silico. The algorithmselected neighbouring compounds of the investigated reaction that had to be produced by alternative biochemical pathways. Using breadth first searches, we tested qualitatively if these products could be generated by reactions that serve as potential deviations of the metabolic flux. With this we identified 70 essential reactions. Our results were compared with a comprehensive list of 38 targets of approved malaria drugs. When combining our approach with an in silico analysis performed recently [Yeh, I., Hanekamp, T., Tsoka, S., Karp, P.D., Altman, R.B., 2004. Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. Genome Res. 14, 917–924] we could improve the precision of the prediction results. Finally we present a refined list of 22 new potential candidate targets for P. falciparum, half of which have reasonable evidence to be valid targets against micro-organisms and cancer

High-speed tunable photonic crystal fiber-based femtosecond soliton source without dispersion pre-compensation

We present a high-speed wavelength tunable photonic crystal fiber-based source capable of generating tunable femtosecond solitons in the infrared region. Through measurements and numerical simulation, we show that both the pulsewidth and the spectral width of the output pulses remain nearly constant over the entire tuning range from 860 to 1160 nm. This remarkable behavior is observed even when pump pulses are heavily chirped (7400 fs^2), which allows to avoid bulky compensation optics, or the use of another fiber, for dispersion compensation usually required by the tuning device.Comment: 8 pages, 11 figure

Quantitative Imaging of Protein-Protein Interactions by Multiphoton Fluorescence Lifetime Imaging Microscopy using a Streak camera

Fluorescence Lifetime Imaging Microscopy (FLIM) using multiphoton excitation techniques is now finding an important place in quantitative imaging of protein-protein interactions and intracellular physiology. We review here the recent developments in multiphoton FLIM methods and also present a description of a novel multiphoton FLIM system using a streak camera that was developed in our laboratory. We provide an example of a typical application of the system in which we measure the fluorescence resonance energy transfer between a donor/acceptor pair of fluorescent proteins within a cellular specimen.Comment: Overview of FLIM techniques, StreakFLIM instrument, FRET application

The role of Cahn and Sivers effects in Deep Inelastic Scattering

The role of intrinsic \bfk_\perp in inclusive and semi-inclusive Deep Inelastic Scattering processes ($\ell p \to \ell h X$) is studied with exact kinematics within QCD parton model at leading order; the dependence of the unpolarized cross section on the azimuthal angle between the leptonic and the hadron production planes (Cahn effect) is compared with data and used to estimate the average values of $k_\perp$ both in quark distribution and fragmentation functions. The resulting picture is applied to the description of the weighted single spin asymmetry $A_{UT}^{\sin(\phi_\pi - \phi_S)}$ recently measured by the HERMES collaboration at DESY; this allows to extract some simple models for the quark Sivers functions. These are compared with the Sivers functions which succeed in describing the data on transverse single spin asymmetries in \pup p \to \pi X processes; the two sets of functions are not inconsistent. The extracted Sivers functions give predictions for the COMPASS measurement of $A_{UT}^{\sin(\phi_\pi - \phi_S)}$ in agreement with recent preliminary data, while their contribution to HERMES $A_{UL}^{\sin\phi_\pi}$ is computed and found to be small. Predictions for $A_{UT}^{\sin(\phi_K - \phi_S)}$ for kaon production at HERMES are also given.Comment: 21 pages, 12 figures, revtex, version published in PRD, one figure, comments and references adde

An in silico Approach to Detect Efficient Malaria Drug Targets to Combat the Malaria Resistance Problem

Resistance to malaria drugs is a major challenging problem in most parts of the world especially in the African continent where about ninety per cent of malaria cases occur. As a response to this alarming problem, the World Health Organisation (W.H.O) recommends that all countries experiencing resistance to conventional monotherapies, such as chloroquine, amodiaquine or sulfadoxine–pyrimethamine, should use combination therapies [1]. Therefore there is a need to discover new drug targets that are able to target the malarial parasite at distinct pathways for an efficient malaria drug. In this paper, we presented a machine-learning tool which is able to identify novel drug targets from the metabolic network of Plasmodium falciparum. With our tool we identified among others 19 drug targets confirmed from literature which we analyzed further with a sophisticated gene expression analysis tool. Our data was clustered using common distance similarity measurements and hierarchical clustering to propose a profound combination of drug targets. Our result suggests that two or more enzymatic reactions from the list of our drug targets which span across about ten pathways (Table 2) could be combined to target at distinct time points in the parasite's intraerythrocytic developmental cycle to detect efficient malaria drug target combination

Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival

Recent evidence suggests CML stem cells are insensitive to kinase inhibitors and responsible for minimal residual disease in treated patients. We investigated whether CML stem cells, in a transgenic mouse model of CML-like disease or derived from patients, are dependent on Bcr-Abl. In the transgenic model, following re-transplantation, donor-derived CML stem cells in which Bcr-Abl expression had been induced and subsequently shut off, were able to persist in vivo and re-initiate leukemia in secondary recipients upon Bcr-Abl re-expression. Bcr-Abl knockdown in human CD34+ CML cells cultured for 12 days in physiological growth factors achieved partial inhibition of Bcr-Abl and downstream targets p-CrkL and p-STAT5, inhibition of proliferation and colony forming cells, but no reduction of input cells. The addition of dasatinib further inhibited p-CrkL and p-STAT5, yet only reduced input cells by 50%. Complete growth factor withdrawal plus dasatinib further reduced input cells to 10%, however the surviving fraction was enriched for primitive leukemic cells capable of growth in long-term culture initiating cell assay and expansion upon removal of dasatinib and addition of growth factors. Together these data suggest that CML stem cell survival is Bcr-Abl kinase independent and suggest curative approaches in CML must focus on kinase-independent mechanisms of resistance

5G-Based Multi-Sensor Platform for Monitoring of Workpieces and Machines: Prototype Hardware Design and Firmware

In this paper, we introduce a 5G-based multi-sensor platform for monitoring workpieces and machines. The prototype is realized within the EU-funded 5G-SMART project, which aims to enable smart manufacturing through 5G, demonstrating and validating new generation network technology in industrial processes. There are already state-of-the-art solutions, but with drawbacks such as limited flexibility, brief real-time capability, and sensors aimed at single applications. The 5G-SMART multi-sensor platform is designed to overcome these points and meet the requirements of Industry 4.0. The device is equipped with different sensors to acquire multiple data from workpieces and machines of the shop floor, wirelessly connected by 5G to the factory cloud. A hardware design description of the prototype is provided, focusing on the electronic components and their interaction with the microcontroller. Verification of the correct functioning of the board is given, with a basic library for the main peripherals used as a basis for the final firmware

EQ-5D-3L Derived Population Norms for Health Related Quality of Life in Sri Lanka

Background Health Related Quality of Life (HRQoL) is an important outcome measure in health economic evaluation that guides health resource allocations. Population norms for HRQoL are an essential ingredient in health economics and in the evaluation of population health. The aim of this study was to produce EQ-5D-3L-derived population norms for Sri Lanka. Method A population sample (n =  780) was selected from four districts of Sri Lanka. A stratified cluster sampling approach with probability proportionate to size was employed. Twenty six clusters of 30 participants each were selected; each participant completed the EQ-5D-3L in a face-to-face interview. Utility weights for their EQ-5D-3L health states were assigned using the Sri Lankan EQ-5D-3L algorithm. The population norms are reported by age and socio-economic variables. Results The EQ-5D-3L was completed by 736 people, representing a 94% response rate. Sixty per cent of the sample reported being in full health. The percentage of people responding to any problems in the five EQ-5D-3L dimensions increased with age. The mean EQ-5D-3L weight was 0.85 (SD 0.008; 95%CI 0.84-0.87). The mean EQ-5D-3L weight was significantly associated with age, housing type, disease experience and religiosity. People above 70 years of age were 7.5 times more likely to report mobility problems and 3.7 times more likely to report pain/discomfort than those aged 18-29 years. Those with a tertiary education were five times less likely to report any HRQoL problems than those without a tertiary education. A person living in a shanty was 4.3 more likely to have problems in usual activities than a person living in a single house. Conclusion The population norms in Sri Lanka vary with socio-demographic characteristics. The socioeconomically disadvantaged have a lower HRQoL. The trends of population norms observed in this lower middle income country were generally similar to those previously reported in high income countries