Laser beam coupling with capillary discharge plasma for laser wakefield acceleration applications

One of the most robust methods, demonstrated up to date, of accelerating electron beams by laser-plasma sources is the utilization of plasma channels generated by the capillary discharges. These channels, i.e., plasma columns with a minimum density along the laser pulse propagation axis, may optically guide short laser pulses, thereby increasing the acceleration length, leading to a more efficient electron acceleration. Although the spatial structure of the installation is simple in principle, there may be some important effects caused by the open ends of the capillary, by the supplying channels etc., which require a detailed 3D modeling of the processes taking place in order to get a detailed understanding and improve the operation. However, the discharge plasma, being one of the most crucial components of the laser-plasma accelerator, is not simulated with the accuracy and resolution required to advance this promising technology. In the present work, such simulations are performed using the code MARPLE. First, the process of the capillary filling with a cold hydrogen before the discharge is fired, through the side supply channels is simulated. The main goal of this simulation is to get a spatial distribution of the filling gas in the region near the open ends of the capillary. A realistic geometry is used for this and the next stage simulations, including the insulators, the supplying channels as well as the electrodes. Second, the simulation of the capillary discharge is performed with the goal to obtain a time-dependent spatial distribution of the electron density near the open ends of the capillary as well as inside the capillary. Finally, to evaluate effectiveness of the beam coupling with the channeling plasma wave guide and electron acceleration, modeling of laser-plasma interaction was performed with the code INF&RNOComment: 11 pages, 9 figure

Ultrafast Internal Conversion in Ethylene. II. Mechanisms and Pathways for Quenching and Hydrogen Elimination

Through a combined experimental and theoretical approach, we study the nonadiabatic dynamics of the prototypical ethylene (C$_2$H$_4$) molecule upon $\pi \rightarrow \pi^*$ excitation with 161 nm light. Using a novel experimental apparatus, we combine femtosecond pulses of vacuum ultraviolet (VUV) and extreme ultraviolet (XUV) radiation with variable delay to perform time resolved photo-ion fragment spectroscopy. In this second part of a two part series, the extreme ultraviolet (17 eV$< h \nu < 23$ eV) probe pulses are sufficiently energetic to break the C-C bond in photoionization, or photoionize the dissociation products of the vibrationally hot ground state. The experimental data is directly compared to ab initio molecular dynamics simulations accounting for both the pump and probe steps. Enhancements of the CH$_2^+$ and CH$_3^+$ photoion fragment yields, corresponding to molecules photoionized in ethylene (CH$_2$CH$_2$) and ethylidene (CH$_3$CH) like geometries are observed within 100 fs after $\pi \rightarrow \pi^*$ excitation. Quantitative agreement between theory and experiment on the relative CH$_2^+$ and CH$_3^+$ yields provides experimental confirmation of the theoretical prediction of two distinct transition states and their branching ratio (Tao, et al. J. Phys. Chem. A. 113, 13656 (2009)). Fast, non-statistical, elimination of H$_2$ molecules and H atoms is observed in the time resolved H$_2^+$ and H$^+$ signals

Spatial and nonspatial implicit motor learning in Korsakoff’s amnesia: evidence for selective deficits

Patients with amnesia have deficits in declarative memory but intact memory for motor and perceptual skills, which suggests that explicit memory and implicit memory are distinct. However, the evidence that implicit motor learning is intact in amnesic patients is contradictory. This study investigated implicit sequence learning in amnesic patients with Korsakoff’s syndrome (N = 20) and matched controls (N = 14), using the classical Serial Reaction Time Task and a newly developed Pattern Learning Task in which the planning and execution of the responses are more spatially demanding. Results showed that implicit motor learning occurred in both groups of participants; however, on the Pattern Learning Task, the percentage of errors did not increase in the Korsakoff group in the random test phase, which is indicative of less implicit learning. Thus, our findings show that the performance of patients with Korsakoff’s syndrome is compromised on an implicit learning task with a strong spatial response component

Carbon nanotube substrates enhance SARS-CoV-2 spike protein ion yields in matrix assisted laser desorption-ionization mass spectrometry

Nanostructured surfaces enhance ion yields in matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS). The spike protein complex, S1, is one fingerprint signature of Sars-CoV-2 with a mass of 75 kDa. Here, we show that MALDI-MS yields of Sars-CoV-2 spike protein ions in the 100 kDa range are enhanced 50-fold when the matrix-analyte solution is placed on substrates that are coated with a dense forest of multi-walled carbon nanotubes, compared to yields from uncoated substrates. Nanostructured substrates can support the development of mass spectrometry techniques for sensitive pathogen detection and environmental monitoring

Cumulative live birth rates in low-prognosis women

STUDY QUESTION: Do cumulative live birth rates (CLBRs) over multiple IVF/ICSI cycles confirm the low prognosis in women stratified according to the POSEIDON criteria? SUMMARY ANSWER: The CLBR of low-prognosis women is ~56% over 18 months of IVF/ICSI treatment and varies between the POSEIDON groups, which is primarily attributable to the impact of female age. WHAT IS KNOWN ALREADY: The POSEIDON group recently proposed a new stratification for low-prognosis women in IVF/ICSI treatment, with the aim to define more homogenous populations for clinical trials and stimulate a patient-tailored therapeutic approach. These new criteria combine qualitative and quantitative parameters to create four groups of low-prognosis women with supposedly similar biologic characteristics. STUDY DESIGN, SIZE, DURATION: This study analyzed the data of a Dutch multicenter observational cohort study including 551 low-prognosis women, aged <44 years, who initiated IVF/ICSI treatment between 2011 and 2014 and were treated with a fixed FSH dose of 150 IU/day in the first treatment cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Low-prognosis women were categorized into one of the POSEIDON groups based on their age (younger or older than 35 years), anti-Müllerian hormone (AMH) level (above or below 0.96 ng/ml), and the ovarian response (poor or suboptimal) in their first cycle of standard stimulation. The primary outcome was the CLBR over multiple complete IVF/ICSI cycles, including all subsequent fresh and frozen-thawed embryo transfers, within 18 months of treatment. Cumulative incidence curves were obtained using an optimistic and a conservative analytic approach. MAIN RESULTS AND THE ROLE OF CHANCE: The CLBR of the low-prognosis women was on average ~56% over 18 months of IVF/ICSI treatment. Younger unexpected poor (n = 38) and suboptimal (n = 179) responders had a CLBR of ~65% and ~68%, respectively, and younger expected poor responders (n = 65) had a CLBR of ~59%. The CLBR of older unexpected poor (n = 41) and suboptimal responders (n = 102) was ~42% and ~54%, respectively, and of older expected poor responders (n = 126) ~39%. For comparison, the CLBR of younger (n = 164) and older (n = 78) normal responders with an adequate ovarian reserve was ~72% and ~58% over 18 months of treatment, respectively. No large differences were observed in the number of fresh treatment cycles between the POSEIDON groups, with an average of two fresh cycles per woman within 18 months of follow-up. LIMITATIONS, REASONS FOR CAUTION: Small numbers in some (sub)groups reduced the precision of the estimates. However, our findings provide the first relevant indication of the CLBR of low-prognosis women in the POSEIDON groups. Small FSH dose adjustments between cycles were allowed, inducing therapeutic disparity. Yet, this is in accordance with current daily practice and increases the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: The CLBRs vary between the POSEIDON groups. This heterogeneity is primarily determined by a woman's age, reflecting the importance of oocyte quality. In younger women, current IVF/ICSI treatment reaches relatively high CLBR over multiple complete cycles, despite reduced quantitative parameters. In older women, the CLBR remains relatively low over multiple complete cycles, due to the co-occurring decline in quantitative and qualitative parameters. As no effective interventions exist to counteract this decline, clinical management currently relies on proper counselling. STUDY FUNDING/COMPETING INTEREST(S): No external funds were obtained for this study. J.A.L. is supported by a Research Fellowship grant and received an unrestricted personal grant from Merck BV. S.C.O., T.C.v.T., and H.L.T. received an unrestricted personal grant from Merck BV. C.B.L. received research grants from Merck, Ferring, and Guerbet. K.F. received unrestricted research grants from Merck Serono, Ferring, and GoodLife. She also received fees for lectures and consultancy from Ferring and GoodLife. A.H. declares that the Department of Obstetrics and Gynaecology, University Medical Centre Groningen received an unrestricted research grant from Ferring Pharmaceuticals BV, the Netherlands. J.S.E.L. has received unrestricted research grants from Ferring, Zon-MW, and The Dutch Heart Association. He also received travel grants and consultancy fees from Danone, Euroscreen, Ferring, AnshLabs, and Titus Healthcare. B.W.J.M. is supported by an National Health and Medical Research Council Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, and Guerbet. He also received a research grant from Merck BV and travel support from Guerbet. F.J.M.B. received monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands) and Ferring Pharmaceuticals BV (the Netherlands) for advisory work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development, and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Not applicable

Watching the acetylene vinylidene intramolecular reaction in real time

It is a long-standing dream of scientists to capture the ultra-fast dynamics of molecular or chemical reactions in real time and to make a molecular movie. With free-electron lasers delivering extreme ultraviolet (XUV) light at unprecedented intensities, in combination with pump-probe schemes, it is now possible to visualize structural changes on the femtosecond time scale in photo-excited molecules. In hydrocarbons the absorption of a single photon may trigger the migration of a hydrogen atom within the molecule. Here, such a reaction was filmed in acetylene molecules (C2H2) showing a partial migration of one of the protons along the carbon backbone which is consistent with dynamics calculations on ab initio potential energy surfaces. Our approach opens attractive perspectives and potential applications for a large variety of XUV-induced ultra-fast phenomena in molecules relevant to physics, chemistry, and biology.Comment: 21 pages, 3 figures, submitte

Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization : an external validation study

We would like to thank the women who participated in the OPTIMIST study and the staff of the participating hospitals for their contributions to the OPTIMIST study.Peer reviewedPostprin

Cumulative live birth rates in low-prognosis women

No external funds were obtained for the present study. The OPTIMIST study was funded by The Netherlands Organization for Health Research and Development (ZonMW number 171102020).Peer reviewedPublisher PD

BRCA1 mutation carriers have a lower number of mature oocytes after ovarian stimulation for IVF/PGD

Purpose The aim of this study was to determine whether BRCA1/2 mutation carriers produce fewer mature oocytes after ovarian stimulation for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), in comparison to a PGD control group. Methods A retrospective, international, multicenter cohort study was performed on data of first PGD cycles performed between January 2006 and September 2015. Data were extracted from medical files. The study was performed in one PGD center and three affiliated IVF centers in the Netherlands and one PGD center in Belgium. Exposed couples underwent PGD because of a pathogenic BRCA1/2 mutation, controls for other monogenic conditions. Only couples treated in a long gonadotropin-releasing hormone (GnRH) agonist-suppressive protocol, stimulated with at least 150 IU follicle stimulating hormone (FSH), were included. Women suspected to have a diminished ovarian reserve status due to chemotherapy, auto-immune disorders, or genetic conditions (other than BRCA1/2 mutations) were excluded. A total of 106 BRCA1/2 mutation carriers underwent PGD in this period, of which 43 (20 BRCA1 and 23 BRCA2 mutation carriers) met the inclusion criteria. They were compared to 174 controls selected by frequency matching. Results Thirty-eight BRCA1/2 mutation carriers (18 BRCA1 and 20 BRCA2 mutation carriers) and 154 controls proceeded to oocyte pickup. The median number of mature oocytes was 7.0 (interquartile range (IQR) 4.0-9.0) in the BRCA group as a whole, 6.5 (IQR 4.0-8.0) in BRCA1 mutation carriers, 7.5 (IQR 5.5-9.0) in BRCA2 mutation carriers, and 8.0 (IQR 6.0-11.0) in controls. Multiple linear regression analysis with the number of mature oocytes as a dependent variable and adjustment for treatment center, female age, female body mass index (BMI), type of gonadotropin used, and the total dose of gonadotropins administered revealed a significantly lower yield of mature oocytes in the BRCA group as compared to controls (p = 0.04). This finding could be fully accounted for by the BRCA1 subgroup (BRCA1 mutation carriers versus controls p = 0.02, BRCA2 mutation carriers versus controls p = 0.50). Conclusions Ovarian response to stimulation, expressed as the number of mature oocytes, was reduced in BRCA1 but not in BRCA2 mutation carriers. Although oocyte yield was in correspondence to a normal response in all subgroups, this finding points to a possible negative influence of the BRCA1 gene on ovarian reserv