Correction of aberration in holographic optical tweezers using a Shack-Hartmann sensor

Optical aberration due to the nonflatness of spatial light modulators used in holographic optical tweezers significantly deteriorates the quality of the trap and may easily prevent stable trapping of particles. We use a Shack-Hartmann sensor to measure the distorted wavefront at the modulator plane; the conjugate of this wavefront is then added to the holograms written into the display to counteract its own curvature and thus compensate the optical aberration of the system. For a Holoeye LC-R 2500 reflective device, flatness is improved from 0.8¿ to ¿/16 (¿=532 nm), leading to a diffraction-limited spot at the focal plane of the microscope objective, which makes stable trapping possible. This process could be fully automated in a closed-loop configuration and would eventually allow other sources of aberration in the optical setup to be corrected for.

Adding functionalities to precomputed holograms with random mask multiplexing in holographic optical tweezers

In this study, we present a method designed to generate dynamic holograms in holographic optical tweezers. The approach combines our random mask encoding method with iterative high-efficiency algorithms. This hybrid method can be used to dynamically modify precalculated holograms, giving them new functionalities¿temporarily or permanently¿with a low computational cost. This allows the easy addition or removal of a single trap or the independent control of groups of traps for manipulating a variety of rigid structures in real time.

Magneto-optical Kerr effect in laser-patterned La2/3Sr1/3MnO3 epitaxial thin films

In this study, we have performed magneto-optical Kerr effect (MOKE) measurement on epitaxial La2/3Sr1/3MnO3 thin films containing artificial interfaces created by laser-patterning the SrTiO3 substrate. The observed increase of the resistivity and of the high-field magnetoresistance when measuring the films across the interface arrays are related to the reduction of the magnetization of the interfaces with respect to the rest of the film. As observed by the local MOKE probe, the structural disorder in the manganite film induced by the underlying patterned substrate leads to a large spin disorder responsible for a strong high-field susceptibility of the resistance.

Intravitreal ranibizumab for age-related macular degeneration - optical coherence tomography guided retreatment intervals and their intra- and inter-individual variability

PURPOSE:To determine whether the need for retreatment after an initial loading phase of 3 monthly intravitreal injections of ranibizumab shows an intra-individual regular rhythm and to what degree it varies between different patients.SETTING:Prospective mono-centre cohort study.METHODS:Prospective study with 42 patients with exudative age-related macular degeneration (AMD), treatment na?ve, giving informed consent. Loading dose of 3 monthly doses of ranibizumab (0,5mg), followed by a 12 months pro re nata (PRN) regimen according to early exudative signs on spectral domain optical coherence tomography (HD-OCT Cirrus Zeiss?, cube 512x126). The follow-up visits were intensified (week 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, etc after each injection) in order to detect exudative recurrences early, and injection followed within 3 days in cases of subretinal fluid, or intraretinal cysts, or central thickness increase of >50?m. Intervals were calculated between injections and the following recurrence was calculated for the 12 month follow-up with PRN treatment. Variability was expressed as standard deviation (SD). RESULTS Visual acuity (VA) improved from a mean ETDRS letter score of 61.6 (SD 10.8) at baseline to 68.0 (SD 10.2, +6.4 letters) at month 3 and increased further to 74.7 (SD 9.0, +13.1 letters from baseline) at month 12. The 15 patients who have completed the study by October 2010 showed maintenance of the VA improvement. Retinal thickness of the central foveal subfield improved from a mean value of 366?m(baseline) to 253?m(month 3), well maintained thereafter. Mean number of injections was 8.8 (SD 3.5) per 12 months of follow-up (after 3 loading doses), ranging from 0 to 12, with mean individual treatment-recurrence intervals ranging from 28 to >365 days (mean 58 days). Intraindividual variability of treatment-recurrence intervals, measured as SD of the individual intervals, was 7.1days as a mean value(range 1.7 ? 22.6 days) for the 33 patients with more than 1 injection during follow-up. SD was higher for longer intervals of an individual patient. It ranged within 20% of the mean intra-individual interval for 30 patients(91%) and within 15% for 21 patients(64%). The first interval was within 1 week of the mean intra-individual interval in 64% of patients and within 2 weeks in 89% of patients.CONCLUSIONS:The majority of AMD patients showed a relatively stable rhythm for PRN injections of intravitreal ranibizumab after initial loading phase, associated with excellent functional and anatomical results. The initial interval between last loading dose and first recurrence may have a predictive value for further need of treatment, therefore potentially facilitating follow-up and patient care.

Design of surface forces apparatus for tribology studies combined with nonlinear optical spectroscopy

We describe the design, calibration, and performance of surface forces apparatus with the capability of illumination of the contact interface for spectroscopic investigation using optical techniques. The apparatus can be placed in the path of a Nd-YAG laser for studies of the linear response or the second harmonic and sum-frequency generation from a material confined between the two surfaces. In addition to the standard fringes of equal chromatic order technique, which we have digitized for accurate and fast analysis, the distance of separation can be measured with a fiber-optic interferometer during spectroscopic measurements (2 Å resolution and 10 ms response time). The sample approach is accomplished through application of a motor drive, piezoelectric actuator, or electromagnetic lever deflection for variable degrees of range, sensitivity, and response time. To demonstrate the operation of the instrument, the stepwise expulsion of discrete layers of octamethylcyclotetrasiloxane from the contact is shown. Lateral forces may also be studied by using piezoelectric bimorphs to induce and direct the motion of one surface.

In vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents and molecular analysis of fluoroquinolone resistance.

OBJECTIVES: To assess the in vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents as well as to dissect the genetic basis of fluoroquinolone resistance. METHODS: Forty-eight human clinical isolates of A. schaalii collected in Switzerland and France were studied. Each isolate was identified by 16S rRNA sequencing. MICs of amoxicillin, ceftriaxone, gentamicin, vancomycin, clindamycin, linezolid, ciprofloxacin, levofloxacin, moxifloxacin, co-trimoxazole, nitrofurantoin and metronidazole were determined using the Etest method. Interpretation of results was made according to EUCAST clinical breakpoints. The quinolone-resistance-determining regions (QRDRs) of gyrA and parC genes were also identified and sequence analysis was performed for all 48 strains. RESULTS: All isolates were susceptible to amoxicillin, ceftriaxone, gentamicin, clindamycin (except three), vancomycin, linezolid and nitrofurantoin, whereas 100% and 85% were resistant to ciprofloxacin/metronidazole and co-trimoxazole, respectively. Greater than or equal to 90% of isolates were susceptible to the other tested fluoroquinolones, and only one strain was highly resistant to levofloxacin (MIC ?32 mg/L) and moxifloxacin (MIC 8 mg/L). All isolates that were susceptible or low-level resistant to levofloxacin/moxifloxacin (n?=?47) showed identical GyrA and ParC amino acid QRDR sequences. In contrast, the isolate exhibiting high-level resistance to levofloxacin and moxifloxacin possessed a unique mutation in GyrA, Ala83Val (Escherichia coli numbering), whereas no mutation was present in ParC. CONCLUSIONS: When an infection caused by A. schaalii is suspected, there is a risk of clinical failure by treating with ciprofloxacin or co-trimoxazole, and ?-lactams should be preferred. In addition, acquired resistance to fluoroquinolones more active against Gram-positive bacteria is possible.

Idarubicin-loaded ONCOZENE drug-eluting embolic agents for chemoembolization of hepatocellular carcinoma: in vitro loading and release and in vivo pharmacokinetics.

PURPOSE: To present in vitro loading and release characteristics of idarubicin with ONCOZENE (CeloNova BioSciences, Inc, San Antonio, Texas) drug-eluting embolic (DEE) agents and in vivo pharmacokinetics data after transarterial chemoembolization with idarubicin-loaded ONCOZENE DEE agents in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Loading efficacy of idarubicin with ONCOZENE DEE agents 100 µm and DC Bead (Biocompatibles UK Ltd, Farnham, United Kingdom) DEE agents 100-300 µm was monitored at 10, 20, and 30 minutes loading time by high-pressure liquid chromatography. A T-apparatus was used to monitor the release of idarubicin from the two types of DEE agents over 12 hours. Clinical and 24-hour pharmacokinetics data were recorded after transarterial chemoembolization with idarubicin-loaded ONCOZENE DEE agents in four patients with unresectable hepatocellular carcinoma. RESULTS: Idarubicin loading in ONCOZENE DEE agents was > 99% at 10 minutes. Time to reach 75% of the release plateau level was 37 minutes ± 6 for DC Bead DEE agents and 170 minutes ± 19 for ONCOZENE DEE agents both loaded with idarubicin 10 mg/mL. After transarterial chemoembolization with idarubicin-loaded ONCOZENE DEE agents, three partial responses and one complete response were observed with only two asymptomatic grade 3 biologic adverse events. Median time to maximum concentration for idarubicin in patients was 10 minutes, and mean maximum concentration was 4.9 µg/L ± 1.7. Mean area under the concentration-time curve from 0-24 hours was equal to 29.5 µg.h/L ± 20.5. CONCLUSIONS: ONCOZENE DEE agents show promising results with very fast loading ability, a favorable in vivo pharmacokinetics profile with a sustained release of idarubicin during the first 24 hours, and encouraging safety and responses. Histopathologic and clinical studies are needed to evaluate idarubicin release around the DEE agents in tumor tissue and to confirm safety and efficacy.

Differential involvement of MEK kinase 1 (MEKK1) in the induction of apoptosis in response to microtubule-targeted drugs versus DNA damaging agents.

MEK kinase 1 (MEKK1) is a 196-kDa enzyme that is involved in the regulation of the c-Jun N-terminal kinase (JNK) pathway and apoptosis. In cells exposed to genotoxic agents including etoposide and cytosine arabinoside, MEKK1 is cleaved at Asp874 by caspases. The cleaved kinase domain of MEKK1, itself, stimulates caspase activity leading to apoptosis. Kinase-inactive MEKK1 expressed in HEK293 cells effectively blocks genotoxin-induced apoptosis. Treatment of cells with taxol, a microtubule stabilizing agent, did not induce MEKK1 cleavage in cells, and kinase-inactive MEKK1 expression failed to block taxol-induced apoptosis. MEKK1 became activated in HEK293 cells exposed to taxol, but in contrast to etoposide-treatment, taxol failed to increase JNK activity. Taxol treatment of cells, therefore, dissociates MEKK1 activation from the regulation of the JNK pathway. Overexpression of anti-apoptotic Bcl2 blocked MEKK1 and taxol-induced apoptosis but did not block the caspase-dependent cleavage of MEKK1 in response to etoposide. This indicates Bcl2 inhibition of apoptosis is, therefore, downstream of caspase-dependent MEKK1 cleavage. The results define the involvement of MEKK1 in the induction of apoptosis by genotoxins but not microtubule altering drugs.

Bonding Agents for Portland Cement Concrete and Mortar, August 1983

Structural repairs of bridges piers and abutments require patching concrete or mortar be placed at various thickness. Whether concrete or mortar is use depends upon the depth of the patch to be made. In some instances, the use of a liquid bonding agent has been specified in the mixes as well as in a grout scrubbed onto the surface to be patched prior to the mix placement. Most of the bonding agents presently approved by the Iowa D.O.T. are polyvinyl acetate (PVA) or some type of latex. In a general discussion with a consultant about various types of bridge repair materials and processes, the subject of bonding agents was discussed at some length. It was the opinion of the consultant that the usage of polyvinyl acetates should be discontinued because of possible deterioration of this material with time. Some of these materials apparently re-emulsify in a high - moisture environment causing serious patch deterioration. As a result of this information, a study was initiated to determine the durability of these materials.

PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents.

The nuclear receptor PPAR alpha is a key regulatory transcription factor in lipid homeostasis, some liver detoxification processes and the control of inflammation. Recent findings suggest that many hypolipidemic drugs and anti-inflammatory agents can potentially act by binding to PPAR alpha and inducing its activity. Here, we identify some structure-function relationships in PPAR alpha, by using the species-specific responsiveness to the two hypolipidemic agents, Wy 14,643 and 5,8,11,14-eicosatetraynoic acid (ETYA). We first show that the species-specific differences are mediated primarily via the ligand binding domain of the receptor and that these two drugs are indeed ligands of PPAR alpha. By mutagenesis analyses we identify amino acid residues in the ligand binding domains of Xenopus, mouse and human PPAR alpha, that confer preferential responsiveness to ETYA and Wy 14,643. These findings will aid in the development of new synthetic PPAR alpha ligands as effective therapeutics for lipid-related diseases and inflammatory disorders.

Role of biological agents in auto-inflammatory disease in children

BACKGROUND: Biological agents (BA) have recently completed the treatment options in auto-inflammatory diseases (AID) in children with the aim to improve the outcome. TNF-α blocking agents have been the first BA successfully used in children. However, other biological agents targeting cytokines including IL-1 and IL-6 have been shown to be effective (anti-IL-1/6), especially in AID like systemiconset juvenile arthritis (SoJIA) or cryopyrine-associated periodic syndrome (CAPS). In Switzerland, Etanercept has been approved for the treatment of JIA since 2000 and Canakinumab for the treatment of paediatric CAPS since 2009.OBJECTIVES: Evaluation of the use of biological agents in AID in Western Switzerland.METHODS: We selected all patients with AID seen in the Réseau Romand de Rhumatologie Pédiatrique (Lausanne, Geneva, Aigle, Sion, and Neuchâtel) who were treated with the following BA: anti-TNF-α (Etanercept, Infliximab, Adalimumab) and Abatacept, and anti-IL-1/6 (Anakinra, Canakinumab, Tocilizumab). We looked at minor and major adverse events and the activity of the disease before and after treatment with BA and with special regards on anti-IL-1/6.RESULTS: Among 921 children and adolescents followed between 2004 and 2010, we selected 85 patients with AID (PFAPA: 40, FMF: 6, HyperIgD: 1, CAPS: 3, SoJIA: 34). Only patients with CAPS and SoJIA were treated with BA. They had a mean age of 9 years (3-22) and F: M ratio of 1.6:1. 7 patients were treated with one BA, 6 patients with 2 different BAs and 3 with 3 BAs. 3 patients with CAPS were treated with anti-IL-1 and responded very well. 13 SoJIA patients were treated with BA (anti-TNF-α: 8, Abatacept: 1, anti-IL-1/6: 8). 4 patients treated by anti-TNF-α were switched to anti-IL-1/6 because of lack of response to treatment (cf Table 1). We did not have any serious adverse events and no serious infections.CONCLUSIONS: Patients with SoJIA and CAPS clearly benefit from treatment with BA. General tolerance was good. In the CAPS group the response to IL-1 was excellent. In SoJIA, 3/4 patients, switched from anti-TNF-α to anti-IL-1/6 for lack of therapeutic response, did not respond well to the second medication. These patientsseem to represent a population relatively resistant to treatment with BA. Due to the low number of patients in our cohort, the response to BA in SoJIA patients non-responder to anti- TNF-α agents should be further studied.