Number Of Additional Experiments Research Articles

Schizandrin A enhances the sensitivity of gastric cancer cells to 5-FU by promoting ferroptosis.

Schizandrin A (Sch A) exert anticancer and multidrug resistance-reversing effects in a variety of tumors, but its effect on 5-fluorouracil (5-Fu) in gastric cancer (GC) cells remains unclear. The aim of the present study was to examine the resistance-reversing effect of Schizandrin A and assess its mechanisms in 5-Fu-resistant GC cells.5-Fu-sensitive GC cells were treated with 5-Fu and 5-Fu-resistant GC cells AGS/5-Fu and SGC7901/5-Fu were were established. These cells were stimulated with Schizandrin A alone or co-treated with 5-Fu and their effect on tumor cell growth, proliferation, migration, invasion and ferroptosis-related metabolism were investigated both in vitro and in vivo. A number of additional experiments were conducted in an attempt to elucidate the molecular mechanism of increased ferroptosis. The results of our study suggest that Schizandrin A in combination with 5-Fu might be useful in treating GC by reverse drug resistance. It was shown that Schizandrin A coadministration suppressed metastasis and chemotherapy resistance in 5-Fu-resistant GC cells through facilitating the onset of ferroptosis, which is an iron-dependent form of cell death, which was further demonstrated in a xenograft nude mouse model. Mechanistically, Schizandrin A co-administration synergistically increased the expression of transferin receptor, thus iron accumulates within cells, leading to lipid peroxidation, which ultimately results in 5-Fu-resistant GC cells death. The results of this study have provided a novel strategy for increasing GC chemosensitivity, indicating Schizandrin A as a novel ferroptosis regulator. Mechanistically, ferroptosis is induced by Schizandrin A coadministration via increasing transferrin receptor expression.

Schizandrin A enhances the sensitivity of gastric cancer cells to 5-FU by promoting ferroptosis

Abstract Objectives The impact of Schizandrin A (Sch A) on 5-fluorouracil (5-Fu) in gastric cancer (GC) cells is not yet understood, despite its known anticancer and multidrug resistance-reversing properties in various tumors. The objective of this study was to investigate the ability of Sch A to reverse resistance and evaluate its mechanisms in GC cells that are resistant to 5-Fu. Methods 5-Fu-sensitive gastric cancer (GC) cells were subjected to treatment with 5-Fu, while 5-Fu-resistant GC cells AGS/5-Fu and SGC7901/5-Fu were successfully developed. In both in vitro and in vivo settings, the impact of Sch A alone or in combination with 5-Fu on tumor cell growth, proliferation, migration, invasion, and ferroptosis-related metabolism was examined by stimulating these cells. A number of additional experiments were conducted in an attempt to elucidate the molecular mechanism of increased ferroptosis. Results Findings from our research indicate that the utilization of Sch A alongside 5-Fu could potentially be beneficial in combating drug resistance and treating GC in a reverse manner. The coadministration of Sch A was demonstrated to inhibit metastasis and chemotherapy resistance in 5-Fu-resistant GC cells by promoting the initiation of ferroptosis, a type of cell death that relies on iron. This effect was also confirmed in a xenograft nude mouse model. Through a mechanistic approach, the combined administration of Sch A exhibited a synergistic effect on enhancing the expression of the transferrin receptor. Consequently, this led to the accumulation of iron within cells, triggering lipid peroxidation and ultimately causing the death of 5-Fu-resistant GC cells. Conclusions In conclusion, the findings from this research have presented a new approach to enhancing GC chemosensitivity, suggesting Sch A as an innovative regulator of ferroptosis. Mechanistically, ferroptosis is induced by Sch A coadministration via increasing transferrin receptor expression.

Is cholesterol good or bad for your brain?--NMDARs have a say.

Is cholesterol good or bad for your brain?--NMDARs have a say.

Optimal allocation of testing resources for statistical simulations

Statistical estimates from simulation involve uncertainty caused by the variability in the input random variables due to limited data. Allocating resources to obtain more experimental data of the input variables to better characterize their probability distributions can reduce the variance of statistical estimates. The methodology proposed determines the optimal number of additional experiments required to minimize the variance of the output moments given single or multiple constraints. The method uses multivariate t-distribution and Wishart distribution to generate realizations of the population mean and covariance of the input variables, respectively, given an amount of available data. This method handles independent and correlated random variables. A particle swarm method is used for the optimization. The optimal number of additional experiments per variable depends on the number and variance of the initial data, the influence of the variable in the output function and the cost of each additional experiment. The methodology is demonstrated using a fretting fatigue example.

Appraising the Effects of the Budget on the Economy with an Econometric Model: The Italian Fiscal Adjustment in the Nineties

This paper describes a procedure for assessing the effects of the budget on economic activity in the short term. Based on counterfactual simulations of an econometric model, the procedure takes into account more relationships between the budget and the economy than other, more synthetic indicators. It not only measures the impact of the budget on output but also evaluates how the budget affects prices and other macroeconomic variables. Moreover, the procedure provides estimates of the effects of specific features of the budget, such as its composition.The procedure is used to appraise the impact of the budget on the Italian economy in the period 1991-2000, using the Bank of Italy’s Quarterly Econometric Model. During the period of fiscal consolidation (1991-97), the impact on GDP growth was generally negative, averaging about -0.6 percentage points (with a spike of -1.4 points in 1995). As fiscal policy relaxed once Italy had succeeded in joining the Monetary Union, the impact on output growth became slightly positive, as in 1998 and 1999, or neutral, as in 2000. Even within the generally restrictive context, the budget exerted a mildly counter-cyclical influence. This result is in line with the findings of previous literature for the 1970s and 1980s. The composition of the budget often played a significant role, in some years amplifying the impact on the primary deficit, in others reducing or even offsetting it. In the period 1991-97, changes in the composition substantially increased the costs of fiscal adjustment. The average impact of the budget on inflation was basically nil in the decade. The results appear significantly different, both quantitatively and qualitatively, from those obtained using the synthetic budget indicators commonly used to assess the fiscal stance. Lastly, a number of additional experiments assess the sensitivity to changes in some key assumptions. In particular, a forward-looking specification of consumers’ behaviour and a forward-looking Taylor-type monetary policy reaction function were estimated and used in the counterfactual simulations. Neither results in significant modifications in the paper’s main conclusions.

Performance assessment of the anticipatory approach to optimal experimental design for model discrimination

The problem of model discrimination arises when several models are proposed to describe one and the same process, a situation encountered in many research fields. To identify the best model from the set of rival models, it may be necessary to collect new information about the process, and thus additional experiments have to be performed. Several approaches have been described in literature to design optimal discriminatory experiments. The anticipatory approach is one of them and is very appealing from a conceptual point of view because the expected information content of the newly designed experiment is considered, even before the experiment is performed (anticipatory design). In this paper, the performance of this approach is evaluated by comparing it with the performance of other, established approaches to optimal experimental design for model discrimination. To conduct this comparison four performance measures were defined: (1) whether the most appropriate model could be identified, (2) the number of additional experiments that have to be designed and performed to achieve model discrimination, (3) the quality of the parameter estimates of the model that is eventually identified as the most appropriate one, and (4) the rate at which the inadequate models are identified. The results clearly indicate that the anticipatory approach has its benefits and may be the preferred approach in many applications in (bio)chemical engineering and in-silico biology.

Radar surface signatures for the two‐dimensional tidal circulation over Phelps Bank, Nantucket shoals: A comparison between theory and experiment

A comparison is made between real aperture radar (RAR) measurements and simulations (based on modeled tidal currents) of radar cross section over a complicated tidal basin (in the vicinity of the Phelps Bank region of the Nantucket shoals) in order to more fully understand the origin of radar signatures that are observed at the ocean surface as a consequence of variations in the topography of the ocean bottom. The Phelps Bank region was mapped under two extreme wind speed conditions: in high winds, in excess of 15 m/s, and in low winds, of the order of 2–3 m/s. For the light‐wind case the measured radar cross section over the west side of the Phelps Bank was enhanced by as much as 20 dB relative to the clutter background. For the high‐wind case, no discernible bathymetric signature was found in the highclutter background. Numerical results for the two‐dimensional M2 (semidiurnal) tidal currents over the Phelps Bank (Greenberg et al., 1989), with ⅛ × ⅛ min of arc resolution, are used as input to the surface signature models: the Alpers and Hennings (1984) first‐order Bragg relaxation model; a generalized form of this relaxation model (in which wind directional effects are incorporated in an approximate manner); and the full‐spectrum model of Lyzenga and Bennett (1988). Comparisons between the models (which do not include wave breaking) and an extreme case of 2–3 m/s winds (where strong wave breaking could become important) reveal that although the models predict correlation between variations in bottom topography and surface signature, they significantly underpredict the magnitude of the observed effect. The model calculations also are very sensitive at low (<2 m/s) wind speeds to the functional form that is assumed for the wind‐wave forcing in the wave action equation. Prior visual observations and measurements of wave spectra (and wave shoaling) in the vicinity of Phelps Bank strongly suggest that the deficiencies of the modeled results that occur explicitly at light winds are due to wave breaking. A number of additional experiments and measurements are suggested for more normal environmental conditions for further theory assessments.

Detection of Intense Ultrasound by the Cod Gadus Morhua

ABSTRACT The ability of cod to detect intense 38kHz pulses was studied in an anechoic tank, using a classical cardiac conditioning method. All 15 cod studied reacted to 3ms pulses. The average threshold was 194.4dB re 1μPa (S.D. 5.4dB, S.E.M. 0.3dB). The data do not reveal the sensory modality involved. A number of additional experiments indicate that the ultrasonic energy per se is the effective stimulus. The threshold is too high for most sources of marine ultrasound to be detected, but is low enough to allow the cod to detect echolocating odontocetes at a range of 10–30m. The results also indicate that cod can detect echo-sounders of the fishing fleet at similar ranges.

Future directions in CP violation

Ongoing experiments seeking CP violating effects in the neuron dipole moment and in ε 1/ ε are at the stage where they will yield critical constraints on attempts to pinpoint the origin of this phenomenon. A number of additional experiments which appear promising in this regard are proposed.

Electron transport across glycerol monooleate bilayer lipid membranes facilitated by magnesium etiochlorin

The transport of electrons across biological membranes is believed to play an important role in many biophenomena. Although there have been many examples of systems which may be transporting electrons across Mueller-Rudin bilayer lipid membranes (blm), none has been well characterized. The system we describe here comprises a glycerol monooleate blm containing a magnesium etiochlorin (Mg-C) separating two aqueous phases each containing ferricyanide, ferrocyanide, KCl, and a platinum electrode. The E0s for the Mg-C+/Mg-C and ferri-/ferrocyanide couples are 0.22 and 0.24 V vs. SCE. Thus the MG-C+/Mb-C system is easily poised by the ferri-/ferrocyanide system. When the potentials of the ferri-/ferrocyanide couples are different on each side of the blm we show that the open-circuit membrane potential nearly equals the difference between the redox potentials. This is unequivocal evidence that electrons are being transferred across the blm from one aqueous phase to the other. On the basis of these experiments we deduce that electron transport is the major charge transport mechanism. When redox potentials are the same on each side of the blm, the conductance of the membrane can be greater than 10(-3) S/cm2. The conductance is proportional to the second power of the concentration of Mg-C in the membrane-forming mixture. A number of additional experiments are described which attempt to elucidate the mechanism of electron transfer. We believe that our data are consistent with the idea of an electron-hopping mechanism in which the transmembrane electron transport occurs by a series of second-order electron transfers between membrane-bound electron donors (Mg-C) and acceptors (Mg-C+). Alternative explanations are presented.

Domain Wall Velocities and the Surface Layer in BaTiO3

The velocity of 180° domain walls in orthorhombic BaTiO3 has been measured over a range of applied fields below 1 kV/cm in dc and in pulsed field conditions. From these measurements it was seen that the domain wall behavior was qualitatively very similar to that reported by Miller and Savage for the tetragonal case. The main difference was the more pronounced effect of the surface layer on the velocities of the walls in the orthorhombic crystals. Accordingly, a number of additional experiments were performed which gave more information on the nature of this surface layer. As a result a completely new model of the surface layer is proposed in which the activation field δL in the layer is much higher than the activation field δB in the bulk of the crystal. The predictions from this model are in satisfactory agreement both with the results reported here for orthorhombic BaTiO3 and with all the evidence available from other sources of the behavior of tetragonal BaTiO3. Comparison is made with previously accepted models and it is shown that these fail to explain many of the experimental results both of the orthorhombic and of the tetragonal cases.

Practical Physics

A DISTINCTIVE feature of this text-book of practical physics is the inclusion of a considerable number of experiments which may be performed by the student at home, using very simple apparatus. In the second edition a supplement has been added containing a number of additional experiments. These are concerned with Fletcher's trolley apparatus, coefficients of friction, Mariotte's bottle, surface tension, expansion of solids, thermal conductivity, photometers, and critical angles. The importance of avoiding eyestrain has not been sufficiently considered in the mathematical tables at the end of the Volume.

Formaldehyde as an oxidation product of chlorophyll extracts

Of recent years the action on carbon dioxide of chlorophyll in vitro has assumed some importance as possibly throwing light on the nature of the photo-synthetic process of green plants. Thus Usher and Priestley have stated that films of extracted chlorophyll in the presence of moist air and carbon dioxide produce formaldehyde and hydrogen peroxide under the influence of light. The earlier work of these authors has been adversely commented upon by several writers, notably by Ewart, to whose criticisms Usher and Priestley have replied with a number of additional experiments and arguments, referring also to the work of Schryver, subsequent to that of Ewart, as affording strong confirmation of their views as far as the synthesis of the aldehyde is concerned. The facts set forth in the present paper came to light during an attempt to confirm and extend the observations of Usher and Priestley and of Schryver. Grass was extracted with alcohol, usually in the cold and in the presence of calcium carbonate. In some experiments the alcoholic liquid was evaporated to dryness under reduced pressure and the residue extracted with ether; in others a solution of chlorophyll in light petroleum was obtained by shaking the alcoholic solution with that liquid. The method of experiment was based upon that described by Schryver, the ether or petroleum extract being allowed to evaporate on glass plates and exposed to light under the various conditions to be mentioned below. As was the case in the later experiments of Usher and Priestley themselves, the test which has been relied upon for the detection of formaldehyde is the very delicate one devised by Schryver, who has found that the reaction is not given by such other members of the series as have been examined up to the present. It has been assumed in the course of these experiments, as in the work of the investigators already mentioned, that the aldehyde produced is formaldehyde, but it is very important that the possibility of the observed effects being due to some other aldehyde or to a mixture of aldehydes should be borne in mind. This point still requires investigation.