1,25(OH)2D3 (vitamin D) appears essential for the normal development of dopaminergic neurons. Vitamin D affects dopamine synthesis and metabolism as well as expression of glial cell line–derived ...neurotrophic factor (GDNF), which is crucial for the survival of dopaminergic neurons. We investigated the role of vitamin D on GDNF and its receptors protooncogene tyrosine–protein kinase receptor Ret (C‐Ret) and GDNF family receptor alpha 1 (GFRα1) signaling. To this end, we used a developmental vitamin D–deficient rat model and SH‐SY5Y cells transfected with vitamin D receptor (VDR). The absence of vitamin D ligand in gestation reduces C‐Ret expression, but not GDNF and GFRα1, in embryo forebrains. Overexpression of VDR in SH‐SY5Y in the absence of ligand (mimicking in vivo developmental vitamin D deficiency) also suppressed C‐Ret mRNA levels. In the presence of vitamin D, C‐Ret mRNA and protein expression were increased. The chromatin immunoprecipitation results suggested that C‐Ret is directly regulated by vitamin D via VDR. GDNF was also increased by vitamin D in these cells. Our small interfering RNA studies showed that knocking down VDR leads to an increase in C‐Ret in the absence of ligand. Finally, we confirmed the inverse relationship between GFRα1 and C‐Ret, as knocking down C‐Ret led to increases in GFRα1 expression. These data extend our knowledge of the diverse and important roles played by vitamin D in dopamine physiology.—Pertile, R.A.N., Cui, X., Hammond, L., Eyles, D.W. Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons. FASEB J. 32, 819–828 (2018). www.fasebj.org
The anti-CD38 antibody daratumumab has been available in Hungary since 2017 for multiple myeloma (MM) patients, used mainly in combinations with lenalidomide or bortezomib. As the majority of ...patients are refractory to lenalidomide by the time of third-line treatment, where daratumumab is financed, we generally prefer the bortezomib (DVd) combination.
To evaluate our real-world results compared to CASTOR study outcomes.
Retrospective overview of the mandatory reporting system for all daratumumab treatments and our own clinical data from January 2017 to May 2023.
University clinic with a myeloma center.
Every patient with MM that received at least 1 cycle of daratumumab in combination with bortezomib and dexamethasone until May 2023 was included (57 patients). We evaluated the number of previous lines of therapy, lenalidomide refractivity, and cytogenetic risk factors.
Hematologic response rates and progression-free survival (PFS).
Unlike in the CASTOR study, where patients received daratumumab in the median second line and only 18% were refractory to lenalidomide, our patients were treated in the median third line and 75% were refractory to lenalidomide. Unsurprisingly, median PFS at our clinic, 11.4 months, proved worse than the median 16.8 months PFS in CASTOR. Remarkably however, the comparison of only third- or fourth-line treated patients showed a significantly better median PFS at our clinic (14.9 vs 9.8 months). This is most likely due to different bortezomib treatment regimens: while in the CASTOR study bortezomib was administered twice a week in the beginning and not at all after 6 months, our protocol included weekly doses at the start and continued bortezomib treatment concurrently with the daratumumab infusions until progression.
A less dose-intensive bortezomib protocol may provoke fewer therapylimiting neuropathies and allow for the continuation of combination therapy, utilizing the synergism of proteasome inhibition and anti-CD38 antibodies and thereby prolonging PFS.
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•A low-cost surface plasmon resonance refractive index sensor based on DVD-ROM has been studied.•Wavelength modulation is used to detect different concentrations of NaCl solution, and ...the sensitivity is 540 nm/RIU.•Angular modulation is also used to detect NaCl solution, and the sensitivity is 32.4 degree/RIU.•FDTD simulation results are in good agreement with the experimental results.
In this paper, a low-cost surface plasmon resonance refractive index sensor based on DVD-ROM is introduced. There is a special grating structure in DVD-ROM, which can be used to excite SPR effect. We have measured the optimal resonance angle of the grating with deionized water at 28°. Wavelength modulation and angle modulation are used to detect different concentrations of sodium chloride solution. The results show that the sensitivities of the two modulation methods are 540 nm/RIU and 32.4 degree/RIU, respectively. Furthermore, we use finite difference time domain method to simulate the two methods separately. The sensitivities are 514 nm/RIU and 30.8 degree/RIU, respectively. The simulation results are in good agreement with the experimental results. Using this method to prepare the detection substrate can greatly reduce the production cost of SPR sensors.
Subscription-based video streaming has recently become the main revenue driver in the home entertainment industry. Whether and how it affects the sales of physical media, which was previously the ...industry's largest revenue source for decades, is still not well understood. We answer this question using a natural experiment that occurred on October 1, 2015, when the content owner Epix switched its streaming partner from Netflix to Hulu. This event created an exogenous shock that significantly reduced the streaming availability of Epix's content because of the difference in the market shares of the two streaming service providers at the time. This occurrence allows us to investigate the causal effect of subscription streaming on physical DVD sales. Our difference-in-differences analysis shows that the decline in the streaming availability of Epix's content caused an increase of 36.07% in its monthly DVD sales during the 15 months after the event. We also find that the cannibalization between these two channels is much stronger for movies with higher level of content stickiness (e.g., more recent titles, and titles with a general audience (G) or parental guidance (PG) rating or belonging to the children/family genre). Our findings provide important implications for content owners on how to balance physical sales with revenues from streaming licenses.
•We use a natral experiment to investigate how subscription-based video streaming affects DVD sales.•The decline in the streaming availability of the content owner Epix’s content caused an increase of 36.07% in its monthly DVD sales during the 15 months after the event.•The cannibalization between these two channels is much stronger for movies with higher level of content stickiness.
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•Patterned substrate can enhance the light absorption leading to improve the optoelectronic devices’ performance.•The mechanism of light absorbed enhancement due to substrate ...architecting was verified.•The photocurrent of patterned photodetector was higher than that of flat one.
ZnO is one of the most fascinating and cost-effective materials for numerous applications, especially optoelectronics. To improve its properties and performance, many techniques have been developed, in which doping and surface engineering are usually of interest. Recently, combining techniques for further enhancement has got significant attention but not fully explored. In this study, a new combination to widen the light absorbance of ZnO nanorods (NRs) is introduced. This combination is based on (i) doping of Mn and (ii) substrate architecting. Patterned substrates are formed with master molds as digital video disc (DVD) and lotus leaf through polydimethylsiloxane (PDMS) molding. Mn-doped ZnO NRs were then hydrothermally grown on them at low temperatures. For investigate their morphology, structure and optical properties, scanning electron microscopy (SEM), X-ray diffraction (XRD), and ultraviolet-visible spectroscopy (UV-Vis) were employed. The obtained results show that the Mn-doped ZnO samples with the patterned substrates own a remarkable increase (> 40%) in the visible light absorbance as compared to that with the flat substrate due to an increment of light scattering. Besides, a photodetector is fabricated based on the optimized patterning PDMS substrate with the active material of Mn doped ZnO NRs. The results show that the photocurrent of patterning device is 3.8 time higher than that of flat substrate. Overall, our approach for growing Mn-doped ZnO NRs on 3D patterned structures at low temperature is promising for optical applications such as flexible and stretchable optoelectronic devices.
This article demonstrates a cost-effective, compact, and handheld smartphone-based sensing tool for accurate estimation of pH values of agricultural farmlands. We develop a spectrometric tool with a ...resolution ability of 0.22 nm/pixel by utilizing 3D printing technology, regular optical components, a Digital Versatile Disc (DVD) as a grating element, and the rear camera of the phone. The sensor responses for standard pH samples within the pH range 4 to 10 are observed to be linear yet yield a sensitivity of 0.129 per pH unit. The resolution of the proposed sensor for the considered samples is observed to be 0.09 pH units. The results obtained from the designed tool while measuring the pH values of six field-collected soil samples are found to be accurate. The designed sensor's performance has been evaluated by comparing the experimental data with the commercial-grade pH sensing tool. With the advantages of being a low-weight and data-sharing ability, we envision that the proposed sensing scheme could emerge as a promising alternative platform for in-field estimation of pH values of soil and water resources of our environment.
•A flexible graphene-based platform for sensitive and selective non-enzymatic detection of H2O2.•Fully integration and customization with easy manufacturing process using laser irradiation.•A ...suitable transducer for migration of electrochemical sensors into areas where flexibility is required.
Here, we demonstrate the detection of H2O2 with a novel, flexible and non-enzymatic electrochemical sensor based on a laser scribed graphene electrode decorated with silver nanoparticles(LSG-Ag). This low-cost technique based on a DVD laser, allowed the direct manufacturing and reduction of graphene oxide into an electrochemical transducer with conductive, lightweight, reduced and flexible characteristics. The LSG-Ag sensor showed a high catalytic response towards H2O2 reduction at -0.5 V with a fast amperometric response of only 3 s. The sensor exhibited a wide linear range from 0.1 to 10 mM (R2 = 0.9982), a low LOD of 7.9 μM with high repeatability of 3% R.S.D. and reproducibility of 4.5% R.S.D. In addition, the LSG-Ag retained its operational characteristics after continuous bending with a loss of current of only 13%. Considering the need of progression of electrochemical systems into trending areas where flexibility is required, the laser-induced sensors can provide a suitable platform for flexible, reliable, sensitive and selective detection.
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