5,507 research outputs found

    Wafer-Level Thermocompression Bonds

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    Thermocompression bonding of gold is a promising technique for achieving low temperature, wafer-level bonding without the application of an electric field or complicated pre-bond cleaning procedure. The presence of a ductile layer influences the fracture behavior of the bonds. The fabrication process was described. In addition, the effect of plasticity was explored by varying the gold bonding thickness between 0.23 to 1.4 µm. Wafers were bonded at 300°C and two different pressures: 1.25 and 7 MPa. The bond toughness of the specimens were characterized using a four-point bend delamination technique. Cohesive failure was found to be the dominant fracture mode in the thicker films. Bonds made with thin gold films failed adhesively and at lower strain energy release rates.Singapore-MIT Alliance (SMA

    Gold Thermocompression Wafer Bonding

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    Thermocompression bonding of gold is a promising technique for the fabrication and packaging microelectronic and MEMS devices. The use of a gold interlayer and moderate temperatures and pressures results in a hermetic, electrically conductive bond. This paper documents work conducted to model the effect of patterning in causing pressure non-uniformities across the wafer and its effect on the subsequent fracture response. A finite element model was created that revealed pattern-dependent local pressure variations of more than a factor of three. This variation is consistent with experimental observations of bond quality across individual wafers A cohesive zone model was used to investigate the resulting effect of non-uniform bond quality on the fracture behavior. A good, qualitative agreement was obtained with experimental observations of the load-displacement response of bonds in fracture tests.Singapore-MIT Alliance (SMA

    Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.

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    DNA methylation patterns change dynamically during mammalian development and lineage specification, yet scarce information is available about how DNA methylation affects gene expression profiles upon differentiation. Here we determine genome-wide transcription profiles during undirected differentiation of severely hypomethylated (Dnmt1⁻/⁻) embryonic stem cells (ESCs) as well as ESCs completely devoid of DNA methylation (Dnmt1⁻/⁻;Dnmt3a⁻/⁻;Dnmt3b⁻/⁻ or TKO) and assay their potential to transit in and out of the ESC state. We find that the expression of only few genes mainly associated with germ line function and the X chromosome is affected in undifferentiated TKO ESCs. Upon initial differentiation as embryoid bodies (EBs) wild type, Dnmt1⁻/⁻ and TKO cells downregulate pluripotency associated genes and upregulate lineage specific genes, but their transcription profiles progressively diverge upon prolonged EB culture. While Oct4 protein levels are completely and homogeneously suppressed, transcription of Oct4 and Nanog is not completely silenced even at late stages in both Dnmt1⁻/⁻ and TKO EBs. Despite late wild type and Dnmt1⁻/⁻ EBs showing a much higher degree of concordant expression, after EB dissociation and replating under pluripotency promoting conditions both Dnmt1⁻/⁻ and TKO cells, but not wild type cells rapidly revert to expression profiles typical of undifferentiated ESCs. Thus, while DNA methylation seems not to be critical for initial activation of differentiation programs, it is crucial for permanent restriction of developmental fate during differentiation

    Integrated Design of Superconducting Magnets with the CERN Field Computation Program ROXIE

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    The program package ROXIE has been developed at CERN for the field computation of superconducting accelerator magnets and is used as an approach towards the integrated design of such magnets. It is also an example of fruitful international collaborations in software development.The integrated design of magnets includes feature based geometry generation, conceptual design using genetic optimization algorithms, optimization of the iron yoke (both in 2d and 3d) using deterministic methods, end-spacer design and inverse field calculation.The paper describes the version 8.0 of ROXIE which comprises an automatic mesh generator, an hysteresis model for the magnetization in superconducting filaments, the BEM-FEM coupling method for the 3d field calculation, a routine for the calculation of the peak temperature during a quench and neural network approximations of the objective function for the speed-up of optimization algorithms, amongst others.New results of the magnet design work for the LHC are given as examples

    Experimental harvesting of fish populations drives genetically based shifts in body size and maturation

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    Size-selective harvesting in commercial fisheries can induce rapid changes in biological traits. While experimental and wild harvested populations often exhibit clear shifts in body size and maturation associated with fishing pressure, the relative contributions of genetic and environmental factors to these shifts remain uncertain and have been much debated. To date, observations of so-called fisheries-induced evolution (FIE) have been based solely on phenotypic measures, such as size data. Genetic data are hitherto lacking. Here, we quantify genetic versus environmental change in response to size-selective harvesting for small and large body size in guppies (Poecilia reticulata) across three generations of selection. We document for the first time significant changes at individual genetic loci, some of which have previously been associated with body size. In contrast, variation at neutral microsatellite markers was unaffected by selection, providing direct genetic evidence for rapid evolution induced by size-selective harvesting. These findings demonstrate FIE in an experimental system, with major implications for the sustainability of harvested populations, as well as impacts on size-structured communities and ecosystem processes. These findings highlight the need for scientists and managers to reconsider the capacity of harvested stocks to adapt to, and recover from, harvesting and predation. © 2013 The Ecological Society of America

    Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

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    ObjectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.MethodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 1011 vg/ml and ≤450 μl per putamen (total dose, ≤7.5 × 1011 vg); cohort 2 received the same concentration (8.3 × 1011 vg/ml) and ≤900 μl per putamen (total dose, ≤1.5 × 1012 vg); and cohort 3 received 2.6 × 1012 vg/ml and ≤900 μl per putamen (total dose, ≤4.7 × 1012 vg). (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography (PET) at baseline and 6 months postprocedure assessed enzyme activity; standard assessments measured clinical outcomes.ResultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.InterpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714

    Negative-index bi-anisotropic photonic metamaterial fabricated by direct laser writing and silver shadow evaporation

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    We present the blueprint for a novel negative-index metamaterial. This structure is fabricated via three-dimensional two-photon direct laser writing and silver shadow evaporation. The comparison of measured linear optical spectra with theory shows good agreement and reveals a negative real part of the refractive index at around 3.85 micrometer wavelength - despite the fact that the metamaterial structure is bi-anisotropic due to the lack of inversion symmetry along its surface normal.Comment: 8 pages, 3 figure

    The antiferromagnetic insulator Ca3FeRhO6: characterization and electronic structure calculations

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    We investigate the antiferromagnetic insulating nature of Ca3FeRhO6 both experimentally and theoretically. Susceptibility measurements reveal a Neel temperature T_N = 20 K, and a magnetic moment of 5.3 muB/f. u., while Moessbauer spectroscopy strongly suggests that the Fe ions, located in trigonal prismatic sites, are in a 3+ high spin state. Transport measurements display a simple Arrhenius law, with an activation energy of 0.2 eV. The experimental results are interpreted with LSDA band structure calculations, which confirm the Fe 3+ state, the high-spin/low-spin scenario, the antiferromagnetic ordering, and the value for the activation energy.Comment: 5 pages, 6 figure

    Effects of spiritual care training for palliative care professionals

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    Little is known about the effects of spiritual care training for professionals in palliative medicine. We therefore investigated prospectively the effects of such training over a six-month period. All 63 participants of the three and a half-day training were asked to fill out three questionnaires: before and after the training, as well as six months later. The questionnaires included demographic data, numeric rating scales about general attitudes towards the work in palliative care, the Self-Transcendence Scale (STS), the spiritual subscale of the Functional Assessment of Chronic Illness Therapy (FACIT-Sp) and the Idler Index of Religiosity (IIR). Forty-eight participants (76) completed all three questionnaires (91 women, median age 49 years; 51 nurses, 16 hospice volunteers, 14 physicians).Significant and sustained improvements were found in self-perceived compassion for the dying (after the training: P =0.002; 6 months later: P=0.025), compassion for oneself (P < 0.001; P =0.013), attitude towards one's family (P =0.001; P =0.031), satisfaction with work (P < 0.001; P =0.039), reduction in work-related stress (P < 0.001; P =0.033), and attitude towards colleagues (P =0.039; P =0.040), as well as in the FACIT-Sp (P < 0.001; P =0.040). Our results suggest that the spiritual care training had a positive influence on the spiritual well-being and the attitudes of the participating palliative care professionals which was preserved over a six-month period
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