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Linear and disturbed flow differentially regulate gene expression, with disturbed flow priming endothelial cells (ECs) for a proinflammatory, atheroprone expression profile and phenotype. Here, we investigated the role of the transmembrane protein neuropilin-1 (NRP1) in ECs exposed to flow using cultured ECs, mice with an endothelium-specific knockout of NRP1, and a mouse model of atherosclerosis. We demonstrated that NRP1 was a constituent of adherens junctions that interacted with VE-cadherin and promoted its association with p120 catenin, stabilizing adherens junctions and inducing cytoskeletal remodeling in alignment with the direction of flow. We also showed that NRP1 interacted with transforming growth factor–β (TGF-β) receptor II (TGFBR2) and reduced the plasma membrane localization of TGFBR2 and TGF-β signaling. NRP1 knockdown increased the abundance of proinflammatory cytokines and adhesion molecules, resulting in increased leukocyte rolling and atherosclerotic plaque size. These findings describe a role for NRP1 in promoting endothelial function and reveal a mechanism by which NRP1 reduction in ECs may contribute to vascular disease by modulating adherens junction signaling and promoting TGF-β signaling and inflammation. Maintaining a quiescent endothelium: Atherosclerosis causes disturbed blood flow that activates inflammatory pathways in endothelial cells, which attracts leukocytes to plaques and exacerbates disease progression. Bosseboeuf et al. investigated the role of the transmembrane protein NRP1 in the response of the endothelium to flow. Under normal flow patterns, NRP1 stabilized protein complexes at cell-cell junctions called adherens junctions and suppressed endothelial inflammation. In mice, NRP1 deficiency was associated with greater numbers of rolling leukocytes on endothelial cells in vitro and in vivo and larger plaque sizes in a model of atherosclerosis. Thus, NRP1 maintains the endothelium in a quiescent state and may limit inflammation in the endothelium under the disturbed blood flow patterns that are characteristic of atherosclerosis. —WW [ABSTRACT FROM AUTHOR]

Interdiffusion in gold/titanium films with titanium evaporated on silicon at different oblique angles (0°, 30°, 50°, and 70°) and gold evaporated under normal incidence is investigated using a scanning electron microscope and in-situ sheet resistance measurements for the optimization of the films' effective gettering ability during and after a low-temperature thermal activation. Films have a tilted columnar structure and a porosity increasing with the deposition angle in agreement with calculated values. The oxygen effective gettering ability, characterized by energy-dispersive X-ray spectroscopy, increases with the deposition angle. It is shown that the gold/titanium film with titanium deposited with an oblique angle of 50° is an optimized condition to obtain the largest sorption capacity after 1 h thermal activation at temperatures lower or equal to 300 °C. This film has a low initial residual stress that becomes highly tensile if thermal activation is performed above 300 °C. [ABSTRACT FROM AUTHOR]

Interdiffusion in gold/titanium films with titanium evaporated on silicon at different oblique angles (0°, 30°, 50°, and 70°) and gold evaporated under normal incidence is investigated using a scanning electron microscope and in-situ sheet resistance measurements for the optimization of the films' effective gettering ability during and after a low-temperature thermal activation. Films have a tilted columnar structure and a porosity increasing with the deposition angle in agreement with calculated values. The oxygen effective gettering ability, characterized by energy-dispersive X-ray spectroscopy, increases with the deposition angle. It is shown that the gold/titanium film with titanium deposited with an oblique angle of 50° is an optimized condition to obtain the largest sorption capacity after 1 h thermal activation at temperatures lower or equal to 300 °C. This film has a low initial residual stress that becomes highly tensile if thermal activation is performed above 300 °C. [ABSTRACT FROM AUTHOR]

Yttrium, titanium, and yttrium-titanium getter thin films were elaborated on silicon by coevaporation in ultrahigh vacuum. Y-Ti films exhibit nanometric crystallites size (18–35 nm) leading to a very high grain boundary density, which is a favorable microstructure for activation at low temperature. The yttrium content in Y-Ti alloys influences grain size, resistance against room temperature oxidation, and gettering performance for oxygen. Y-Ti films with an yttrium content higher than 30% show strong oxygen sorption during annealing at low temperature (<300 °C). After 1 h of annealing at 250 °C, it was estimated that the yttrium-based getter films can trap between 0.2 and 0.5 μmol of oxygen per cm2, while no oxygen sorption was detected for a single metal titanium film. This makes Y-Ti getter alloys attractive candidates for the packaging of MEMS under vacuum with a low bonding temperature. [ABSTRACT FROM AUTHOR]

A process able to produce at wafer scale patterned electrodes on the vertical sidewalls of trenches is described and investigated in detail. It is based on metal evaporation at oblique incidence through a shadow mask made in a dry photoresist film. A full model of the deposition and patterning process is established in order to map the shape as well as the thickness and density of patterned electrodes with or without wafer rotation. In the case of wafer rotation, the modelling is based on the analogy of each shadow mask edge with the gnomon of a sundial. The final electrode shape is then computed from the trajectories followed by the shadows of the gnomons. Offset of the substrate tilt axis with respect to substrate plane, and position on the wafer surface, are considered in the analysis, as well as the variation of film density with incidence angle. Advantages and limitations of the proposed process are discussed. It is shown that sidewall electrodes isolated or connected to top or bottom electrodes can be simply achieved by a suitable sizing and alignment of the shadow mask but that close electrodes on a given sidewall cannot be mutually isolated when the substrate is rotated. The patterning process is demonstrated in the case of Au/Cr electrodes on the sidewalls of through wafer trenches made in GaAs by deep reactive ion etching. [ABSTRACT FROM AUTHOR]

Previous studies showed that monoclonal immunoglobulins G (IgGs) of "monoclonal gammopathy of undetermined significance" (MGUS) and myeloma were hyposialylated, thus presumably pro-inflammatory, and for about half of patients, the target of the monoclonal IgG was either a virus—Epstein–Barr virus (EBV), other herpes viruses, hepatitis C virus (HCV)—or a glucolipid, lysoglucosylceramide (LGL1), suggesting antigen-driven disease in these patients. In the present study, we show that monoclonal IgAs share these characteristics. We collected 35 sera of patients with a monoclonal IgA (6 MGUS, 29 myeloma), and we were able to purify 25 of the 35 monoclonal IgAs (6 MGUS, 19 myeloma). Monoclonal IgAs from MGUS and myeloma patients were significantly less sialylated than IgAs from healthy volunteers. When purified monoclonal IgAs were tested against infectious pathogens and LGL1, five myeloma patients had a monoclonal IgA that specifically recognized viral proteins: the core protein of HCV in one case, EBV nuclear antigen 1 (EBNA-1) in four cases (21.1% of IgA myeloma). Monoclonal IgAs from three myeloma patients reacted against LGL1. In summary, monoclonal IgAs are hyposialylated and as described for IgG myeloma, significant subsets (8/19, or 42%) of patients with IgA myeloma may have viral or self (LGL1) antigen-driven disease. [ABSTRACT FROM AUTHOR]

Sheet resistance of transition metal-based getter films was recorded during 1 h 15 min of activation at 250 °C by in situ 4-probes measurement under vacuum. Co-evaporated alloys of Zr–Ti, Zr–V and Zr–Co with different compositions were studied. Results show that resistivity and temperature coefficient of resistance (TCR) are linked and follow the Mooij rule. A gradual disorder in the structure was deduced from the less disordered—pure metals then Zr–Ti then Zr–V—to the highest, i.e. Zr–Co. A specific study of Zr–Ti showed that the grain size directly impacts TCR and resistivity of as-deposited film, and oxygen content after activation at 250 °C. For Zr–V and Zr–Co, the amorphous structure has to be taken into account and it has been shown that too much disorder in the structure is detrimental for sorption ability. The most oxidized films no longer follow the Mooij rule after annealing. [ABSTRACT FROM AUTHOR]

A large set of micro- and nanodevices requires hybrid vacuum packaging at the wafer level to optimize their performance and lifetime. When the temperature of the packaging fabrication process is limited, getter films must be integrated into the packaging cavity to obtain a low and sustainable pressure. In this paper, gas generation and residual gases inside a wafer-level package, as well as the main getter alloy films and multilayers investigated previously, are reviewed. An emphasis is put on the effect of a gaseous environment on the physicochemical mechanisms involved in getter film activation and gas sorption. A large outgassing occurs during the packaging fabrication process. It produces a gas load larger than or similar to that generated during the entire lifetime of the device at room temperature. The resulting partial pressures of gases in a micropackage are quite different from those found in ultrahigh vacuum during characterization by surface analysis techniques and when getter films are used in accelerators. Consequently, in micropackages, activation and sorption steps can no longer be analyzed separately and surface oxidation and/or oxygen bulk diffusion during activation should be taken into account. It is thus recommended to use and develop complementary characterization techniques that enable the investigation of surface and bulk phenomena at various temperatures, pressures, and gas mixtures for the assessment of getter films for vacuum packaging. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) and its pre-cancerous stage monoclonal gammopathy of undetermined significance (MGUS) allow to study immune responses and the chronology of inflammation in the context of blood malignancies. Both diseases are characterized by the production of a monoclonal immunoglobulin (mc Ig) which for subsets of MGUS and MM patients targets pathogens known to cause latent infection, a major cause of inflammation. Inflammation may influence the structure of both polyclonal (pc) Ig and mc Ig produced by malignant plasma cells via the sialylation of Ig Fc fragment. Here, we characterized the sialylation of purified mc and pc IgGs from 148 MGUS and MM patients, in comparison to pc IgGs from 46 healthy volunteers. The inflammatory state of patients was assessed by the quantification in serum of 40 inflammation-linked cytokines, using Luminex technology. While pc IgGs from MGUS and MM patients showed heterogeneity in sialylation level, mc IgGs from both MGUS and MM patients exhibited a very low level of sialylation. Furthermore, mc IgGs from MM patients were less sialylated than mc IgGs from MGUS patients (p < 0.01), and mc IgGs found to target an infectious pathogen showed a lower level of sialylation than mc IgGs of undetermined specificity (p = 0.048). Regarding inflammation, 14 cytokines were similarly elevated with a p value < 0.0001 in MGUS and in MM compared to healthy controls. MM differed from MGUS by higher levels of HGF, IL-11, RANTES and SDF-1-α (p < 0.05). MGUS and MM patients presenting with hyposialylated pc IgGs had significantly higher levels of HGF, IL-6, tumor necrosis factor-α, TGF-β1, IL-17, and IL-33 compared to patients with hyper-sialylated pc IgGs (p < 0.05). In MGUS and in MM, the degree of sialylation of mc and pc IgGs and the levels of four cytokines important for the anti-microbial response were correlated, either positively (IFN-α2, IL-13) or negatively (IL-17, IL-33). Thus in MGUS as in MM, hyposialylation of mc IgGs is concomitant with increased levels of cytokines that play a major role in inflammation and anti-microbial response, which implies that infection, inflammation, and abnormal immune response contribute to the pathogenesis of MGUS and MM. [ABSTRACT FROM AUTHOR]

Cu-Sn intermetallic diffusion has been studied with thin Sn and Cu films deposited by physical vapor deposition. It was found that annealing time is critical to the interdiffusion of copper and tin, leading to the formation of CuSn and CuSn phases at temperatures of interest. Based on this observation, test wafer bonding have been implemented at 320 and 250 °C with sealing pressures of 0.6, 2, 4, 6 and 10 MPa. The experiments emphasized the importance of the sealing pressure and the existence of a sealing pressure threshold for the success of the bonding. When the sealing pressure was superior to that threshold, at 250 °C a thin (<4 µm) bonded Cu/CuSn/Cu joint was obtained, with none of the voiding defects previously reported by using electroplating. [ABSTRACT FROM AUTHOR]

The next-to-last sentence in the first paragraph on pg. 054202-4 should read, "The shift in the peak positions of 222 Y SB 2 sb O SB 3 sb and 002 Y after annealing is also evident from XRD measurements." Erratum: "Electrical and ion beam analyses of yttrium and yttrium-titanium getter thin films oxidation" [J. Vac. XRD analysis of evaporated yttrium films after different exposures to oxygen. [Extracted from the article]

In dogfish, spermatogenesis progresses from a restricted germinative zone, which lines the dorsal testicular vessel. Single spermatogonia (As), including the spermatogonial stem cells (SSCs), produce successively paired (Ap), undifferentiated (Au4 to Au512), and differentiated (Ad1 to Ad8) spermatogonia and preleptotene (PL) spermatocytes through 13 mitoses. Dogfish spermatogonial subpopulations present classical morphological characteristics but cannot be distinguished on the basis of molecular markers. This characterization has been initiated in mammals despite the difficulty to separate each spermatogonial subpopulation. For instance, both glial cell-derived neurotrophic factor family receptor alpha 1 (GFRα1) and promyelocytic leukemia zinc finger protein (PLZF) are markers of undifferentiated spermatogonia, whereas receptor tyrosine kinase C-kit is a marker of differentiated spermatogonia. The aim of this study is to characterize spermatogonial markers and to differentiate several spermatogonial subpopulations. Dogfish cDNA sequences have been identified and validated by phylogenetic analyses for gfra1, plzf, pou2, as well as for high-mobility group box proteins 2 and 3 (hmgb2 and 3) and for mini-chromosome maintenance protein 6 (mcm6). We have used the anatomical advantage of the polarized dogfish testis to analyze the expression of those markers by RT-PCR and in situ hybridization. gfra1, pou2, and plzf have been detected in the testicular germinative zone, suggesting that spermatogonial markers are relatively well conserved among vertebrates but with a less restricted expression for plzf. Moreover, hmgb3 and mcm6 have been identified as new markers of differentiated spermatogonia. Finally, this first molecular characterization of spermatogonial subpopulations in a chondrichthyan model will be useful for further studies on the SSC niche evolution. [ABSTRACT FROM AUTHOR]

Non-absorbing beam splitters integrated on silicon are desirable for various micro-opto electro mechanical systems (MOEMS) devices. In this paper, we demonstrate the manufacturing with a 100% yield of dielectric membranes having a diameter up to 5.9 mm and an approximately 50% reflectivity in the 570-900 nm wavelength range. The membranes are made from a stack of up to 12 alternating SiNx and SiO2 plasma enhanced chemical vapor deposition (PECVD) films deposited and annealed on silicon. Backside micromachining of the silicon wafer by deep reactive ion etching followed by XeF2 etching is used to release the membranes. Annealing effects on stress variation and hydrogen bonding in PECVD single films and multilayers were investigated in detail to get a multilayer stack with controlled tensile stress. Optical measurements of the reflectivity, flatness and vibrations of these membranes show that they are suitable for use in MOEMS devices working in the visible-near infrared range. [ABSTRACT FROM AUTHOR]

Electrostatically actuated microelectromechanical systems (MEMS) devices integrating a surface micromachined silicon nanowire were batch processed to investigate motion detection with a nanowire piezoresistive gauge. In the proposed implementation, the nanogauge is indirectly coupled to the MEMS structure through an intermediate coupling spring. This design allows an arbitrary choice of MEMS motion detection range and a resolution improvement of in situ nanowire gauge factor measurements. Using this approach, it is demonstrated that an in-plane MEMS displacements up to 180 nm with a noise level down to 0.7 \\rm\AA/\Hz^1/2 can be achieved. MEMS resonance measurement in air and in vacuum by this method is also demonstrated. Results are compared with ex situ measurements of MEMS displacement by optical microscopy and by integrated capacitive detection.\hfill[2012-0206] [ABSTRACT FROM AUTHOR]