The oil-water (O-W) interface interaction of 1 wt% tea saponin (TS) and different monoglyceride (MAG) concentrations (0%–5%) was studied and further explored its relationship with emulsion gel ...properties. A combination of several analytical techniques such as microscopy, rheology, and infrared spectroscopy was used for macro and micro characterization of samples, respectively. Low concentrations (1%–3%) of MAG with TS had synergistic effects on the emulsification, the interface was dominated by fibrillar network of TS assembly though the co-adsorption of TS with the appropriate MAG. A combination of interfacial interaction and viscosity enhancement endowed obtained emulsion gels with improved properties, such as overall lower droplet size, homogeneous appearance, and better response to external deformations. However, in the presence of high MAG concentrations (4%–5%), interfacial films were readily subjected to the MAG crystal piercing, and with a reduced strength finally owing to the increasing distance and weakened hydrogen bonding of TS molecules. Besides, the interface and the subsequent formation and property of systems would be dominated by MAG. Thus, emulsion gels exhibited weak gel strength and declined stability. Because the number of protruding MAG crystals as well as the protruding distance was enhanced when the MAG content increased, droplet surface was completely destroyed and a collapsed system were formed. It was revealed that TS/MAG mixtures displayed interesting MAG concentration-dependence interfacial behaviors, which were closely related to the formation and stabilization of emulsions/emulsion gels. These findings would provide valuable information for the stabilization of emulsion gels involved in natural saponins.
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•The interface behavior was closely related to the property of TS-MAG emulsion gels.•The stability of TS emulsion gels greatly improved with increasing MAG concentration.•The interface and property of systems were dominated by MAG upon excessive MAG.
Objective: We sought to determine the prevalence, clinical features, and laboratory characteristics of polyneuropathies in Waldenström’s macroglobulinaemia (WM), a malignant bone marrow disorder with ...lymphocytes that produce monoclonal IgM. Methods: We prospectively studied 119 patients with WM and 58 controls. Medical history was taken, and neurological examinations, electrodiagnostic tests, and serum studies were performed by different examiners who were blinded to results except the diagnosis of WM. Results: Polyneuropathy symptoms, including discomfort and sensory loss in the legs, occurred more frequently (p<0.001) in patients with WM (47%) than in controls (9%). Patients with WM had 35% lower quantitative vibration scores, and more frequent pin loss (3.4 times) and gait disorders (5.5 times) than controls (all p<0.001). Patients with IgM binding to sulphatide (5% of WM) had sensory axon loss; those with IgM binding to myelin associated glycoprotein (MAG) (4% of WM) had sensorimotor axon loss and demyelination. Patients with WM with IgM binding to sulphatide (p<0.005) or MAG (p<0.001) had more severe sensory axon loss than other patients with WM. Demyelination occurred in 4% of patients with WM with no IgM binding to MAG. Age related reductions in vibration sense and sural SNAP amplitudes were similar (∼30%) in WM and controls. Conclusions: Peripheral nerve symptoms and signs occur more frequently in patients with WM than controls, involve sensory modalities, and are often associated with gait disorders. IgM binding to MAG or sulphatide is associated with a further increase in the frequency and severity of peripheral nerve involvement. Age related changes, similar to those in controls, add to the degree of reduced nerve function in patients with WM.
Lap welding is employed to join thin plate materials in car assemblies. The quality of welding depends on its conditions and seam tracking in the welding line. An arc sensor was employed by ...oscillating the welding torch in a thick weld. Since the welding torch was not oscillated in the welding of thin plate materials, the arc sensor could not be applied to lap welding. To trace the welding line, the weld pool in pulsed metal active gas (MAG) welding under the shielding gas of Ar 80% and CO2 20% was pictured using a CMOS camera. The weld pool was observed in the rear to the welding direction. The features of the weld pool were investigated to recognize the welding line. Since the arc affected the brightness of the weld pool, the timing of the shutter of the CMOS camera was synchronized with the current waveform to take clear weld pool images. The welding line was detected using an image processing method. In this paper, a banalization method and a pattern matching method was investigated. The pattern matching method is useful than the binarization method. A digital controller was designed to trace the welding line. The validity of the proposed method was verified by carrying out a tracking experiment.
Calcium (Ca2+) is an essential mineral of endoplasmic reticulum (ER) luminal biochemistry because of the Ca2+ dependence of ER-resident chaperones charged with folding de novo proteins that transit ...this cellular compartment. ER Ca2+ depletion reduces the ability of chaperones to properly fold the proteins entering the ER, thus leading to an accumulation of misfolded proteins and the onset of a state known as ER stress. However, not all conditions that cause ER stress do so in a manner dependent on ER Ca2+ depletion. Agents such as tunicamycin inhibit the glycosylation of de novo polypeptides, a key step in the maturation process of newly synthesized proteins. Despite this established effect of tunicamycin, our understanding of how such conditions modulate ER Ca2+ levels is still limited. In the present study, we report that a variety of ER stress–inducing agents that have not been known to directly alter ER Ca2+ homeostasis can also cause a marked reduction in ER Ca2+ levels. Consistent with these observations, protecting against ER stress using small chemical chaperones, such as 4-phenylbutyrate and tauroursodeoxycholic acid, also attenuated ER Ca2+ depletion caused by these agents. We also describe a novel high-throughput and low-cost assay for the rapid quantification of ER stress using ER Ca2+ levels as a surrogate marker. This report builds on our understanding of ER Ca2+ levels in the context of ER stress and also provides the scientific community with a new, reliable tool to study this important cellular process in vitro.
Background
Anti‐myelin‐associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety ...and maximum tolerated dose (MTD) in anti‐MAG neuropathy.
Methods
This phase 1b, open‐label, single‐arm, dose‐finding trial was conducted from 2019 through 2022. The original design included a dose‐escalation/extension phase followed by a dose‐expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD.
Results
Eleven patients enrolled (10 men), with a mean age of 67.6 years (SD = 6.18, range 58–77 years) and mean disease duration of 8.5 years (SD = 10.9, range 1–40 years). The study terminated early due to higher‐than‐expected non‐dose‐limiting toxicity venous thromboembolism (VTE) events. The calculated MTD was 25 mg (posterior mean of toxicity probability was 0.01 with a 95% credible interval of 0.00, 0.06), but a recommended phase 2 dose of 15 mg was advised. For secondary exploratory outcomes, only EQ‐5D (−0.95, 95% CI −1.81 to −0.09) and total IgM (−162 mg/dL, 95% CI −298 to −26) showed signs of improvement by month 12.
Conclusions
Lenalidomide was associated with higher‐than‐expected VTE events in anti‐MAG neuropathy patients, despite a calculated MTD of 25 mg. A recommended phase 2 dose of 15 mg was advised. Lenalidomide did not improve disability or impairment at 12 months, although this study was not powered for efficacy. The risks of long term lenalidomide may outweigh benefit for patients with anti‐MAG neuropathy. Any future efficacy study should address VTE risk, as current myeloma guidelines appear inadequate.
Trial Registration
Lenalidomide in Anti‐MAG Neuropathy: Phase 1b Study, ClinicalTrials.gov Identifier: NCT03701711, https://clinicaltrials.gov/ct2/show/NCT03701711. First submitted October 10, 2018. First patient enrolled in January 2019.
As part of the European Space Agency׳s ROSETTA Mission the Lander PHILAE touched down on comet 67P/Churyumov–Gerasimenko on November 12, 2014. The magnetic field has been measured onboard the orbiter ...and the lander. The orbiter׳s tri-axial fluxgate magnetometer RPC-MAG is one of five sensors of the ROSETTA Plasma Consortium. The lander is also equipped with a tri-axial fluxgate magnetometer as part of the ROSETTA Lander Magnetometer and Plasma-Monitor package (ROMAP). This unique setup makes a two point measurement between the two spacecrafts in a relatively small distance of less than 50km possible. Both magnetometers were switched on during the entire descent, the initial touchdown, the bouncing between the touchdowns and after the final touchdown. We describe a method for attitude determination by correlating magnetic low-frequency waves, which was tested under different conditions and finally used to reconstruct PHILAE׳s attitude during descent and after landing. In these cases the attitude could be determined with an accuracy of better than ±5°. These results were essential not only for PHILAE operations planning but also for the analysis of the obtained scientific data, because nominal sources for this information, like solar panel currents and camera pictures could not provide sufficient information due to the unexpected landing position.
•PHILAE׳s attitude was reconstructed with magnetic field data from ROMAP and RPC-MAG.•The accuracies where better than ±5°, which was higher than other possible methods.•This was important for scientific data evaluation and i.e. RF Link establishment.
The effect on the microstructure and mechanical properties of direct-bonded magnesia-chrome refractories of additions of nanostructured MgCr2O4 and FeCr2O4 is reported. The nanostructured additives, ...synthesized by the citrate-nitrate route and calcined at several different temperatures, were characterized by XRD, BET and TEM. Additions of 0.5 and 1 wt % of these nanostructured oxides were made to magnesia-chrome refractories and calcined at 1650 OC in a shuttle kiln. Their microstructures were analyzed by SEM/EDX and their physical and mechanical properties (permanent linear change (PLC), bulk density, apparent porosity, cold crushing strength (CCS) and hot modulus of rupture (HMOR) were determined according to the respective DIN standards. The addition of the nanostructured oxides to the magnesia-chrome refractories facilitated the formation of secondary spinels, influencing the physical and mechanical properties. FeCr2O4 additions increased the size of the secondary spinel due to liquid phase formation in the presence of magnetite impurities in the FeCr2O4 nano-powder. The addition of nano-sized MgCr2O4 and FeCr2O4 to the base formulation of the refractory increased the CCS from 67.4 MPa to 82.8 MPa and 81.0 MPa respectively, while nano-sized MgCr2O4 increased the HMOR value from 5.48 MPa to 5.91 MPa and nano-sized FeCr2O4 increased the HMOR from 5.48 MPa to 5.72 MPa. This smaller increase than that obtained with FeCr2O4 additions is attributed to liquid phase formation in the presence of magnetite, as observed by XRD.
Background
International consensus on IgM ± anti‐MAG ± PNP (IgM PNP) is lacking. Despite increasing interest in clinical trials, validated disease‐specific measures are needed to adequately capture ...limitations and changes over time. The IMAGiNe (IgM ± anti‐myelin associated glycoprotein MAG peripheral neuropathy) study surges as an international collaboration to create a standardized registry of patients with IgM ± anti‐MAG PNP. The consortium, which currently consists of 11 institutions from 7 countries, presents here the IMAGiNe study design and protocol.
Aims
Functional outcome measures will be constructed at the level of impairment, as well as activity and participation. We aim to describe the natural history of the cohort, the role of anti‐MAG antibodies, the presence of clinical subtypes, and potential biomarkers.
Methods
The IMAGiNe study is a prospective, observational cohort study with a 3‐year follow‐up. At each assessment, researchers collect clinical data and subjects complete a list of preselected outcome measures. Among these, the “Pre‐Rasch‐built Overall Disability Scale (Pre‐RODS)” questionnaire will be submitted to Rasch analysis to assess classic and modern clinimetric requirements.
Results
The final measures will include the IgM‐PNP‐specific RODS and Ataxia Rating Scale (IgM‐PNP‐ARS). Descriptions of the disease course, clinical heterogeneity, treatment regimes, variations in laboratory values, and antibody titers will help reach consensus on diagnosis and follow‐up strategies.
Conclusion
The constructed interval scales will be cross‐culturally valid and suitable for use in future clinical trials and daily practice. The ultimate goals are to improve functional individualized assessment, reach international consensus, and lay the foundations for successful designs in future studies.
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