Higher Rs Values Research Articles

Identification of lipid metabolism-related gene signature in the bone marrow microenvironment of multiple myelomas through deep analysis of transcriptomic data

Dysregulated lipid metabolism in the bone marrow microenvironment (BMM) plays a vital role in multiple myeloma (MM) development, progression, and drug resistance. However, the exact mechanism by which lipid metabolism impacts the BMM, promotes tumorigenesis, and triggers drug resistance remains to be fully elucidated.By analyzing the bulk sequencing and single-cell sequencing data of MM patients, we identified lipid metabolism-related genes differential expression significantly associated with MM prognosis, referred to as LMRPgenes. Using a cohort of ten machine learning algorithms and 117 combinations, LMRPgenes predictive models were constructed. Further exploration of the effects of the model risk score (RS) on the survival status, immune status of patients with BMM, and response to immunotherapy was conducted. The study also facilitated the identification of personalized therapeutic strategies targeting specified risk categories within patient cohorts.Analysis of the scRNA-seq data revealed increased lipid metabolism-related gene enrichment scores (LMESs) in erythroblasts and progenitor, malignant, and Tprolif cells but decreased LMESs in lymphocytes. LMESs were also strongly correlated with most of the 50 hallmark pathways within these cell populations. An elevated malignant cell ratio and reduced lymphocytes were observed in the high LMES group. Moreover, the LMRPgenes predictive model, consisting of 14 genes, showed great predictive power. The risk score emerged as an independent indicator of poor outcomes. Inverse relationships between the RS and immune status were noted, and a high RS was associated with impaired immunotherapy responses. Drug sensitivity assays indicated the effectiveness of bortezomib, buparlisib, dinaciclib, staurosporine, rapamycin, and MST-312 in the high-RS group, suggesting their potential for treating patients with high-RS values and poor response to immunotherapy. Ultimately, upon verification via qRT-PCR, we observed a significant upregulation of ACBD6 in NDMM group compared to the control group.Our research enhances the knowledge base regarding the association between lipid metabolism-related genes (LMRGs) and the BMM in MM patients, offering substantive insights into the mechanistic effects of the BMM mediated by LMRGs.Graphical abstract

Map conformational landscapes of intrinsically disordered proteins with polymer physics quantities

Disordered proteins are conformationally flexible proteins that are biologically important and have been implicated in devastating diseases such as Alzheimer’s disease and cancer. Unlike stably folded structured proteins, disordered proteins sample a range of different conformations that needs to be accounted for. Here, we treat disordered proteins as polymer chains, and compute a dimensionless quantity called instantaneous shape ratio (Rs), as Rs = Ree2/Rg2, where Ree is end-to-end distance and Rg is radius of gyration. Extended protein conformations tend to have high Ree compared with Rg, and thus have high Rs values, whereas compact conformations have smaller Rs values. We use a scatter plot of Rs (representing shape) against Rg (representing size) as a simple map of conformational landscapes. We first examine the conformational landscape of simple polymer models such as Random Walk, Self-Avoiding Walk, and Gaussian Walk (GW), and we notice that all protein/polymer maps lie within the boundaries of the GW map. We thus use the GW map as a reference and, to assess conformational diversity, we compute the fraction of the GW conformations (fC) covered by each protein/polymer. Disordered proteins all have high fC scores, consistent with their disordered nature. Each disordered protein accesses a different region of the reference map, revealing differences in their conformational ensembles. We additionally examine the conformational maps of the nonviral gene delivery vector polyethyleneimine at various protonation states, and find that they resemble disordered proteins, with coverage of the reference map decreasing with increasing protonation state, indicating decreasing conformational diversity. We propose that our method of combining Rs and Rg in a scatter plot generates a simple, meaningful map of the conformational landscape of a disordered protein, which in turn can be used to assess conformational diversity of disordered proteins.

Abstract P2-15-02: Using Oncotype DX Breast Recurrence Score® (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR+) breast cancer (BC)

Abstract Background:Adjuvant endocrine therapy remains the standard of care for patients (pts) with early stage, HR+ BC who can safely omit chemotherapy based on RS results; however, the role of NET remains unclear. There are limited data regarding the optimal duration of treatment with NET and the ideal patient (pt) population for NET in terms of age and RS result. This question rose to critical importance amidst the COVID-19 pandemic, during which NET was utilized more broadly in attempts to delay surgery or chemotherapy while preserving optimal pt outcomes. This study re-examines the use of NET among a cohort of pts with HR+ BC randomized to NET or neoadjuvant chemotherapy (NCT) based on RS (performed on initial core biopsy specimens).Methods:Data were pooled from two independent studies performed at Emory’s Winship Cancer Institute and Massey Cancer Center at Virginia Commonwealth University (VCU) from 2010-2012. These studies evaluated rates of clinical and pathologic complete response (pCR) among pts with early stage, HR+ BC assigned to treatment groups based on RS results. Pts with RS 0-10 received NET (Group (Grp) A), RS 11-24/25 (Emory 11-24 vs VCU 11-25) were randomized to NET (Grp B) or NCT (Grp C), and those with RS 25/26-100 received NCT (Grp D). Associations between RS result, neoadjuvant therapy and pCR in the breast, lymph nodes (LN) and breast plus LN were evaluated using Fisher’s exact test. Results:109 pts were included in this analysis. The Emory cohort was younger (median age 56 years (yrs) vs 63 yrs in VCU cohort) and more diverse (37.5% African American (AA) vs 18.6% AA in VCU cohort). The pts were predominantly post-menopausal (69.6% Emory vs 83.1% VCU). Nodal status among the Emory cohort was evenly divided with 50% N0 and 50% N+, while the majority of VCU pts were N0 (76.3% N0 vs 22.0% N+). Pts were grouped based on RS result: RS <11 (18% Emory vs 20.3% VCU), RS 11-24/25 (36% Emory vs 55.9% VCU) and RS 24/25 or higher (46% Emory vs 23.7% VCU). Pts with low RS result were older (median 64 yrs vs 59 yrs among RS > 24/25) with higher percentage of low-grade tumors (47.6% grade 1 vs 5.4% grade 1 among RS >24/25). With regard to pCR, there were no significant differences among pts with low or intermediate RS results, as no pts in these groups achieved pCR in the breast or breast + LN (Table). Pts with RS result 25/26-100 (Grp D) were the only pts shown to achieve pCR in breast + LN (18.9%, p= 0.0043 across groups). Notably, while pts on the Emory study received longer courses of NET (median 10 months vs 5.5 months), there were no significant differences in pCR across RS result subgroups noted between the two institutions. Conclusion:Our results demonstrate that the use of Oncotype DX Breast Recurrence Score® or other genomic assays in the neoadjuvant setting may help guide treatment decisions when considering the use of NET versus NCT. Pt age and length of endocrine therapy as well as pt preferences should be considered when determining neoadjuvant treatment plans. There are currently ongoing studies evaluating the use of NET with CDK4/6 inhibitors that will offer further insight into optimal neoadjuvant treatment strategies in HR+ BC. Subsequent phase III evaluation of the role of genomic assays in the neoadjuvant setting is feasible and may help determine whether NET + CDK 4/6 inhibitors could replace NCT for pts with higher RS values. Table: pCR according to treatment groups (All Eligible Patients)VariableGroup A (N=21)Group B (N=23)Group C (N=22)Group D (N=37)P value (a)pCR Breast0 (0.0%)0 (0.0%)0 (0.0%)8 (21.6%)0.0016pCR Nodes0 (0.0%)1 (4.3%)3 (13.6%)2 (5.6%)0.2977pCR Breast + Nodes0 (0.0%)0 (0.0%)0 (0.0%)7 (18.9%)0.0043(a) Fisher's exact test was used for categorical variables with cell counts <5.Note: Group A= Recurrence Score <11,Group B= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NET,Group C= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NCT,and Group D= Recurrence Score >24 (Emory study) or >25 (VCUstudy).Note: 1 patient did not receive SLNB(sentinel lymph node biopsy) or ALND (axillary lymph node dissection) and is excluded from the denominator for pCR Nodes. Citation Format: Caitlin Taylor, Aimee Foreman, Christy Russell, Dipankar Bandyopdhyay, Xiaoyan Deng, Lisa Floyd, Amelia Zelnak, Ruth O'Regan, Harry Bear, Jane Meisel. Using Oncotype DX Breast Recurrence Score® (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR+) breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-02.

Investigation of electrical values of low-efficiency dye-sensitized solar cells (DSSCs)

Indium-tin-oxide (ITO)/density (d)- titanium dioxide (TiO2)/nonporous (nonp)-TiO2 is a TiO2-based bilayer photoanode. These photoanodes coated for dye-sensitized solar cells (DSSCs) were with nonp-TiO2 surface and had very thick ITO layer. DSSCs were fabricated with these photoanodes. After their current density-voltage (J-V) were analyzed, ıt was seen that they were low efficiency and the shape of their J-V curve was linear line instead of rectangle. In this study, it was examined the relationship between the dark current (IDC), the series resistance (Rs) and the shunt resistance (Rsh) were examined for evaluating the fill factor (FF) of low-efficiency DSSCs because of the photoanodes with nonp-TiO2 surfaces and very thick ITO for contact layer. It was seen in the J-V graph of DSSCs which had low FF value due to their IDC and low Rsh. The J-V graph of low-efficiency DSSCs is linear due to their low Rsh and high Rs values. Moreover, the too thick ITO layer decreases the resistance of photoanodes; however, electrons in these photoanodes can not efficiently transferred to external circuit from ITO contact layer of DSSCs.

Spatial-Temporal Changes of Soil Respiration across China and the Response to Land Cover and Climate Change

Soil respiration (Rs) plays an important role in the carbon budget of terrestrial ecosystems. Quantifying the spatial and temporal variations in Rs in China at the regional scale helps improve our understanding of the variations in terrestrial carbon budgets that occur in response to global climate and environmental changes and potential future control measures. In this study, we used a regional-scale geostatistical model that incorporates gridded meteorological and pedologic data to evaluate the spatial Rs variations in China from 2000 to 2013. We analysed the relationship between Rs and environmental factors, and suggest management strategies that may help to keep the terrestrial carbon balance. The simulated results demonstrate that the mean annual Rs value over these 14 years was 422 g/m2/year, and the corresponding total amount was 4.01 Pg C/year. The Rs estimation displayed a clear spatial pattern and a slightly increasing trend. Further analysis also indicated that high Rs values may occur in areas that show a greater degree of synchronicity in the timing of their optimal temperature and moisture conditions. Moreover, cultivated vegetation exhibits higher Rs values than native vegetation. Finally, we suggest that specific conservation efforts should be focused on ecologically sensitive areas where the Rs values increase significantly.

Survival of resistant starch during the processing of atmospheric and vacuum fried instant noodles

Abstract The objective was to develop instant noodles (IN) made by atmospheric and vacuum frying processes, with addition of 10% of three different sources of resistant starch: resistant starch type 2 (RS2), resistant starch type 3 (RS3) and green banana flour (GBF) aiming the increasing of the fibre content. The IN obtained by atmospheric frying lost water faster and absorbed more fat. However, for both frying treatments, the RS3 noodles absorbed the least amount of oil. The greatest loss of RS occurred during the cooking stage. RS2 and GBF noodles presented a loss of RS of around 30% during steam cooking, while the RS3 approximately 18%. The frying process decreased RS content of noodles, however, during both frying process, the samples with the highest RS content at all frying times were noodles containing RS3. When comparing products obtained after 90 and 120 s of atmospheric and vacuum frying, respectively, it was observed that, although the frying time in vacuum process was longer, higher RS values were obtained for the three different formulations. The vacuum frying process has advantages due to the lower fat absorption (3% less), lighter colour and a reduced conversion of RS to digestible starch, compared to atmospheric frying.

The sensitivity of soil respiration to soil temperature, moisture, and carbon supply at the global scale.

Soil respiration (Rs) is a major pathway by which fixed carbon in the biosphere is returned to the atmosphere, yet there are limits to our ability to predict respiration rates using environmental drivers at the global scale. While temperature, moisture, carbon supply, and other site characteristics are known to regulate soil respiration rates at plot scales within certain biomes, quantitative frameworks for evaluating the relative importance of these factors across different biomes and at the global scale require tests of the relationships between field estimates and global climatic data. This study evaluates the factors driving Rs at the global scale by linking global datasets of soil moisture, soil temperature, primary productivity, and soil carbon estimates with observations of annual Rs from the Global Soil Respiration Database (SRDB). We find that calibrating models with parabolic soil moisture functions can improve predictive power over similar models with asymptotic functions of mean annual precipitation. Soil temperature is comparable with previously reported air temperature observations used in predicting Rs and is the dominant driver of Rs in global models; however, within certain biomes soil moisture and soil carbon emerge as dominant predictors of Rs. We identify regions where typical temperature-driven responses are further mediated by soil moisture, precipitation, and carbon supply and regions in which environmental controls on high Rs values are difficult to ascertain due to limited field data. Because soil moisture integrates temperature and precipitation dynamics, it can more directly constrain the heterotrophic component of Rs, but global-scale models tend to smooth its spatial heterogeneity by aggregating factors that increase moisture variability within and across biomes. We compare statistical and mechanistic models that provide independent estimates of global Rs ranging from 83 to 108Pgyr-1 , but also highlight regions of uncertainty where more observations are required or environmental controls are hard to constrain.

Novel Design for Centrifugal Counter-Current Chromatography: VI. Ellipsoid Column

A novel ellipsoid column was designed for centrifugal counter-current chromatography. Performance of the ellipsoid column with a capacity of 3.4 mL was examined with three different solvent systems composed of 1-butanol–acetic acid–water (4:1:5, v/v/v) (BAW), hexane–ethyl acetate–methanol-0.1 M HCl (1:1:1:1, v/v/v/v) (HEMH), and 12.5% (w/w) PEG1000 and 12.5% (w/w) dibasic potassium phosphate in water (PEG-DPP) each with suitable test samples. In dipeptide separation with BAW system, both stationary phase retention (Sf) and peak resolution (Rs) of the ellipsoid column were much higher at 0° column angle (column axis parallel to the centrifugal force) than at 90° column angle (column axis perpendicular to the centrifugal force), where elution with the lower phase at a low flow rate produced the best separation yielding Rs at 2.02 with 27.8% Sf at a flow rate of 0.07 mL/min. In the DNP-amino acid separation with HEMW system, the best results were obtained at a flow rate of 0.05 ml/min with 31.6% Sf yielding high Rs values at 2.16 between DNP-DL-glu and DNP-β-ala peaks and 1.81 between DNP-β-ala and DNP-L-ala peaks. In protein separation with PEG-DPP system, lysozyme and myolobin were resolved at Rs of 1.08 at a flow rate of 0.03 mL/min with 38.9% Sf. Most of those Rs values exceed those obtained from the figure-8 column under similar experimental conditions previously reported.

P2-12-26: Impact of the Recurrence Score on Adjuvant Decision-Making in ER-Positive Early Breast Cancer – Results of a Large Prospective Multicentre Decision Impact Study in Node Negative and Node Positive Disease.

Abstract Background Oncotype DX® has become part of clinical routine in the diagnosis and decision-making progress in early breast cancer (EBC). Prospective data on its clinical use and impact on treatment decisions in ER-positive (ER+) node negative (N0) disease from various controlled clinical trials in different countries have been published recently. The Recurrence Score® (RS) has also been validated as a prognostic and predictive marker for patients with ER+ node positive (N+) disease. As of today no prospective data have been reported on its impact on decision making in these patients. We performed a large prospective study to evaluate RS-guided adjuvant therapy in N0 and N+ ER+ EBC. Material and Methods: Patients (pts) with ER+, HER2−negative N0 and N+ (1-3 positive lymph nodes) EBC and no contraindication for adjuvant chemotherapy were included in the study. Physicians’ adjuvant treatment recommendations and their confidence in these as well as patients’ decisional conflicts were assessed before and after knowledge of the results of the test using standardized questionnaires. Actual treatment data were collected to perform pharmacoeconomic analyses. Analyses were performed on the per-protocol population for whom a Recurrence Score result and treatment recommendations pre and post-test were available. Results: Overall 379 pts were recruited. In 11 pts Oncotype DX could not be performed and 2 pts dropped out leaving 366 pts in the per protocol population. Of these, 244 (66.7%) were N0 and 122 (33.3%) N+. Median age was 56 years (Range 25–85). Overall, 54.1% had low, 38.0% intermediate and 7.9% high RS values. For N0 disease, the distribution of RSs was 53.7%, 38.9%, 7.4% and for N+ disease 54.9%, 36.9% and 9.0%, respectively. Initial treatment recommendation changed in 33.1% of all cases; 30.3% in N0 and 38.5% in N+ disease, and in 36.4% for pts with low, 30.9% with intermediate and 20.7% with high RSs. In 21.6% of all pts a recommendation for adjuvant chemoendocrine therapy (CHT) was changed to endocrine therapy (HT), 10.7% of recommendations changed from HT to CHT. For N0 disease change rates were 18.4% from CHT to HT and 11.5% from HT to CHT. For N+ disease 27.9% of recommendations changed from CHT to HT and 9.0% of recommendations changed from HT to CHT. In 25% of all, 22% of N0 and 39% of N+ pts initially recommended HT the post-RS recommendation changed to CHT; in 38% of all, 39% of N0 and 37% of N+ pts initially recommended CHT the recommendation changed to HT. Overall, physicians’ confidence increased in 45.1% of all (p=0.047) and 44.7 of N0 and 45.9% of N+ cases, respectively. There was a moderate decrease of the decisional conflict score in all pts and subgroups that reached statistical significance for all pts (p=0.029) and the low RS subgroup (p=0.003). Conclusions: Results of this large prospective study show an impact of the RS on adjuvant treatment decision making in German clinical practice for patients with ER+ EBC. Recommendations were predominantly changed from chemoendocrine to endocrine adjuvant therapy resulting in a net reduction of chemotherapy usage. This effect was more pronounced for patients with 1–3 positive nodes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-26.

Cluster radius and sampling radius in the determination of cluster membership probabilities

We analyze the dependence of the membership probabilities obtained from kinematical variables on the radius of the field of view around open clusters (the sampling radius, Rs). From simulated data, we show that the best discrimination between cluster members and non-members is obtained when the sampling radius is very close to the cluster radius. At higher Rs values more field stars tend to be erroneously assigned as cluster members. From real data of two open clusters (NGC 2323 and NGC 2311) we obtain that the number of identified cluster members always increases with increasing Rs. However, there is a threshold Rs value above which the identified cluster members are severely contaminated by field stars and the effectiveness of membership determination is relatively small. This optimal sampling radius is \sim 14 arcmin for NGC 2323 and \sim 13 arcmin for NGC 2311. We discuss the reasons for such behavior and the relationship between cluster radius and optimal sampling radius. We suggest that, independently of the method used to estimate membership probabilities, several tests using different sampling radius should be performed in order to evaluate the existence of possible biases.

CO2 gasification of Thai coal chars: Kinetics and reactivity studies

Two sized fractions (<75 µm and 150-250 µm) of Ban Pu lignite A and Lampang subbituminous B coals were pyrolyzed in a drop tube fixed bed reactor under nitrogen atmosphere at 500-900 o C. Gasification of coal chars with excess carbon dioxide was then performed at 900-1,100 o C. The result was analyzed in terms of reactivity index, reaction rate and activation energy. It was found that chars at lower pyrolysis temperature had highest carbon conver- sion, and for chars of the same sized fraction and at the same pyrolysis temperature, reactivity indices increased with gasification temperature. The lower rank Ban Pu lignite A had higher Rs values than higher rank Lampang subbitumi- nous B coals. Smaller chars from both coals had higher Rs values, due to the higher ash content. At present, it can be concluded that, within the gasification temperature range studied, gasification rates of chars obtained at various py- rolysis temperatures showed a linear correlation with temperature. However, additional experiment is needed to verify the correlation.

High resolution for single-strand conformation polymorphism analysis by capillary electrophoresis.

Since the successful completion of the Human Genome Project, increasing concern is being directed toward the polymorphic aspect of the genome and its clinical relevance. A form of single-strand DNA-conformation polymorphism analysis (SSCP) employing nondenaturing slab-gel electrophoresis (SGE) is applicable to the genetic diagnosis of bladder cancer from urine samples. To bring this technique into routine clinical practice, the use of capillary electrophoresis (CE) is naturally favorable in terms of speed and automation. However, the resolving power of SSCP, a prerequisite basis for reliability required in diagnostics, remains as a challenge for CE systems. We thus focused on this topic and conducted studies on CE instruments equipped with a single capillary or an array of multiple capillaries, using the resolution (Rs) as a quantitative scale for the resolving power. Polymer concentration and buffer are shown to be the decisive parameters. High Rs values of >2.5 are achieved for representative SNPs markers under the optimized conditions, without sacrificing such intrinsic advantages of CE over SGE as the 10-fold quicker migration time and operation that is reproducible, continuous, and automatic. The strategies presented broaden the limits of CE in both the current and related applications.

Direct chiral resolution of phenylalkylamines using a crown ether chiral stationary phase.

A direct, isocratic high-performance liquid chromatographic method is described for the enantiomeric resolution of a number of phenylalkylamines, namely, racemic cathinone, amphetamine, norephedrine, and norphenylephrine, without sample derivatization. The separations were achieved on an S-18-crown-6-ether chiral stationary phase known as CR(+). The chromatographic parameters alpha (separation factor) and Rs (resolution factor) lay within a narrow range for all compounds used in this study except for cathinone, which resulted in high alpha and Rs values. The recognition mechanism for this column involves the interaction of the crown structure with a charged primary ammonium ion. The stereochemical structures of the compounds in this study contribute to the results obtained for the chromatographic parameters, especially in cathinone's case. This paper will discuss the recognition mechanism contributing to the high alpha and Rs, values obtained for cathinone.

Variation in the Growth Potential in a Timothy and Red Clover Mixture

Abstract Growth potentials (Rs) in leys at five sites in northern Sweden were determined by using a growth model. The Rs value is independent of the current weather, and is related to stand vigour and depends on the growth cycle, species, age of the ley, soil fertility and winter survival. Timothy (Phleum pratense L.) and a mixture of red clover (Trifolium pratense L.) and timothy at different nitrogen fertilizations were investigated. In the spring growth the Rs value was higher in the red clover mixture than in timothy and lower in the first- than in the second-year leys. In the regrowth the Rs value was considerably higher (25%) in the first- than in the second-year leys. Higher Rs values occurred at sites with higher contents of humus than at sites with lower humus content. Interpretation of results from field experiments could be improved by determination of the growth potential (Rs).