bluuebunny/crossref_metadata_2025 huggingface dataset:
ZHX2 mediates proteasome inhibitor resistance via regulating nuclear translocation of NF‐κB in multiple myeloma
Authors: Jiang Jifeng , Sun Yifeng , Xu Jiadai , Xu Tianhong , Xu Zhao , Liu Peng
Published: August 2020

Background

Multiple myeloma (MM) is an incurable hematological malignancy. Although proteasome inhibitors and immunomodulators have significantly improved patient outcomes, some patients respond poorly to treatment and almost all patients will relapse. Mechanisms of proteasome inhibitor resistance in multiple myeloma have not been fully elucidated. ZHX2 is a transcription regulator degraded via proteasome and presents both oncogenic or tumor suppressive effect in different cancers, however, it is still unknown that the role of ZHX2 in myeloma. In this study, we aim to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM.

Methods

GSE24080 gene expression profile datasets from Gene Expression Omnibus (GEO) were analyzed to evaluate the relationship between ZHX2 expression level and survival in MM. Expression of ZHX2 in human MM cell lines at baseline and after bortezomib (BTZ) treatment was determined by Western blotting (WB). The proliferation and apoptosis rate of MM cells treated with BTZ after the knockdown of ZHX2 were analyzed by flow cytometry. Nuclear translocation of NF‐κB after the knockdown of ZHX2 was evaluated by WB and immunofluorescence, and the expression of NF‐κB target genes was measured by real‐time quantitative PCR. Co‐immunoprecipitation (Co‐IP) and WB were used to detect the interaction of ZHX2 with NF‐κB.

Results

We found that higher ZHX2 expression was correlated with poorer clinical outcomes of patients. In addition, ZHX2 expression was relatively higher in RPMI‐8226 and MM.1S cell lines and the level of ZHX2 protein was upregulated after BTZ treatment. Knockdown of ZHX2 significantly enhanced the sensitivity of MM cells to BTZ, inhibited nuclear translocation of NF‐κB, and reduced mRNA expression of NF‐κB target genes. It was also revealed that ZHX2 directly binds to NF‐κB.

Conclusion

Our study showed that ZHX2 can promote proteasome inhibitor resistance in MM cells by regulating the nuclear translocation of NF‐κB.
Identification of potential prognostic small nucleolar RNA biomarkers for predicting overall survival in patients with sarcoma
Authors: Liu Jianwei , Liao Xiwen , Zhu Xianze , Lv Peizhen , Li Rong
Published: August 2020

Objective

The main purpose of the present study is to screen prognostic small nucleolar RNA (snoRNA) markers using the RNA‐sequencing (RNA‐seq) dataset of The Cancer Genome Atlas (TCGA) sarcoma cohort.

Methods

The sarcoma RNA‐seq dataset comes from the TCGA cohort. A total of 257 sarcoma patients were included into the prognostic analysis. Multiple bioinformatics analysis methods for functional annotation of snoRNAs and screening of targeted drugs, including biological network gene ontology tool, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and connectivity map (CMap) are used.

Results

We had identified 15 snoRNAs that were significantly related to the prognosis of sarcoma and constructed a prognostic signature based on four prognostic snoRNA (U3, SNORA73B, SNORD46, and SNORA26) expression values. Functional annotation of these four snoRNAs by their co‐expression genes suggests that some of them were closely related to cell cycle‐related biological processes and tumor‐related signaling pathways, such as Wnt, mitogen‐activated protein kinase, target of rapamycin, and nuclear factor‐kappa B signaling pathway. GSEA of the risk score suggests that high risk score phenotype was significantly enriched in cell cycle‐related biological processes, protein SUMOylation, DNA replication, p53 binding, regulation of DNA repair, and DNA methylation, as well as Myc, Wnt, RB1, E2F, and TEL pathways. Then we also used the CMap online tool to screen five targeted drugs (rilmenidine, pizotifen, amiprilose, quipazine, and cinchonidine) for this risk score model in sarcoma.

Conclusion

Our study have identified 15 snoRNAs that may be serve as novel prognostic biomarkers for sarcoma, and constructed a prognostic signature based on four prognostic snoRNA expression values.
A methylomics‐associated nomogram predicts recurrence‐free survival of thyroid papillary carcinoma
Authors: Chen Hengyu , Ma Xianxiong , Yang Ming , Wang Mengyi , Li Lei , Huang Tao
Published: August 2020

Background

Thyroid papillary carcinoma (TPC) is the most common type of thyroid cancer (TC). The prognosis of TPC patients with tumor‐cell metastasis is poor. Therefore, this study aims to develop a model for predicting TPC patients' recurrence‐free survival (RFS).

Methods

We included 546 TPC patients who were clinically and pathologically diagnosed with TPC. The methylation biomarkers that associate with RFS were explored. These 546 samples were divided into training dataset (first 70%) and validation dataset (remaining 30%) randomly. The training dataset was used to identify prognostic biomarkers and construct risk prediction model, in addition, the validation dataset was used to verify the predictive performance of the model. We used Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify the significant predictive biomarkers, and establish the relapse risk prediction model from the identified biomarkers.

Results

A 6‐DNA methylation signature yielded a high evaluative performance for RFS. The Kaplan‐Meier analysis indicated that the 6‐DNA methylation signature could significantly distinguish the high‐ and low‐risk patients in training, validation and entire sets. In addition, a nomogram was constructed based on risk score, metastasis status and residual tumor status, and C‐index, receiver operating characteristic (ROC) and the calibration plots analysis which demonstrated the good performance and clinical utility of the nomogram.

Conclusions

The results suggested that the 6‐DNA methylation signature is the independent prognostic marker for RFS and functioned as a significant tool for guiding the clinical treatment of TPC patients.
Application of response surface methodology for optimization of ultrasound‐assisted solid‐liquid extraction of phenolic compounds from Cenostigma macrophyllum
Authors: Moreira Bruno Oliveira , Barbosa Filho Marco Roberto Dourado , de Carvalho Anaildes Lago , da Silva Douglas Gonçalves , Cruz Mariluze Peixoto , Yatsuda Regiane , David Jorge Mauricio
Published: August 2020

This study determines the optimal conditions for the ultrasound‐assisted solid‐liquid extraction (UA‐SLE) of the total phenolic compounds (TPC) of Cenostigma macrophyllum leaves. The experiments were carried out according to three‐level, four‐variable Box‐Behnken design combined with the response surface methodology (RSM). Extraction (sonication) time, liquid‐solid ratio, methanol concentration, and ultrasonic power were investigated as independent variables to obtain the optimal extraction conditions for TPC. Data were fitted to a second‐order polynomial model, and the model fitness was evaluated by the analysis of variance, which indicated the model (P < 0.0001), presenting precision and reliability with the experiments performed (R2 = 0.9947, coefficient of variance [CV] = 4.29, SD = 1.67). Individual and interactive effects of the independent variables on TPC extraction were interpreted using the proposed mathematical model. The results showed that for the maximum TPC extraction, the optimal conditions included 32 min extraction time, 29.73 mL·g−1 liquid‐solid ratio, 47.72% methanol concentration, and 145.71 W ultrasonic power. Under these optimal conditions, the predicted values were in agreement with the experimental values, thus validating the RSM model. When the optimal conditions were compared with those of conventional extraction techniques, the results showed that UA‐SLE presented significantly better results for TPC extraction (71.2% to 138.3% more efficient) and for antioxidant activity (115.0% to 179.2% more efficient). High‐performance liquid chromatography analysis of the extracts revealed that UA‐SLE did not interfere with the extract chemical composition, thus confirming that it was more effective than conventional techniques.
Planar tomography and numerical analysis for damage characterization of impact loaded RC plates
Authors: Nerger Deborah , Moosavi Robabeh , Bracklow Franz , Hering Marcus , Kühn Tino , Curbach Manfred , Hille Falk , Rogge Andreas
Published: August 2020

The damage analysis of reinforced concrete (RC) is of high interest for reasons of effective maintenance and structural safety of buildings. The damage structures of RC plates loaded by an impact were investigated, applying X‐ray planar tomography and finite element method (FEM). Planar tomography allows getting three‐dimensional information of the RC elements and the damage including crack, spalling, and scabbing. The FEM model validated on the tomography data justifies the application for further predictions of the damage description. In this study, we investigated concrete plates of three different thickness subjected to impacts at different low‐ and medium‐velocity, whereby the used impactor had a flat tip, which resulted in small penetrations on the front side and scabbing on the rear side. In order to quantify the damage, the damage volume and its distribution through the plate were computed and the correlations between degree of damage and impact velocity were found out.
The impact of chronic kidney disease on outcomes following peripheral vascular intervention
Authors: Narcisse Dennis I. , Weissler Elizabeth Hope , Rymer Jennifer A. , Armstrong Ehrin J. , Secemsky Eric A. , Gray William A. , Mustapha Jihad A. , Adams George L. , Ansel Gary M. , Patel Manesh R. , Jones William Schuyler
Published: August 2020

Background

Patients with chronic kidney disease (CKD) have worsened clinical outcomes following percutaneous coronary intervention; however, limited evidence exists in patients undergoing peripheral vascular intervention (PVI).

Purpose

We aimed to assess the effect of CKD on outcomes following PVI for symptomatic peripheral artery disease.

Methods

Using patients from the LIBERTY 360 study, we compared the rates of 30 day and 1 year major adverse vascular events (MAVE), a composite of all‐cause mortality, major amputation, and target vessel/lesion revascularization, between patients with and without CKD (estimated glomular filtration rate less than 60) following PVI. Multivariable adjustment was performed to assess for independent association between CKD and outcomes.

Results

Among 1189 patients enrolled, 378 patients (31.8%) had CKD. At 1 year, patients with CKD had higher rates of MAVE (34.6% vs 25.6%), all‐cause mortality (11.9% vs 5.5%), and major amputation (5.9% vs 2.6%) when compared with patients without CKD (all P < .05). After adjustment, patients with CKD had higher risks of 1‐year MAVE (HR 1.30, 95% CI 1.04‐1.64; P = .023) and all‐cause mortality (HR 1.88, 95% CI 1.22‐2.91; P = .005) when compared with patients without CKD. There was no statistically significant difference in risk of major amputations (HR 1.70, 95% CI 0.91‐3.17; P = .094).

Conclusions

Despite high procedural success and low amputation rates, patients with CKD remain at greater risk for MAVE and all‐cause mortality after PVI. Further research is needed to determine treatment strategies to mitigate substantial mortality risk in this vulnerable population.
A Novel Prodrug of a nNOS Inhibitor with Improved Pharmacokinetic Potential
Authors: Maccallini Cristina , Marinelli Lisa , Indorf Patrick , Cacciatore Ivana , Fantacuzzi Marialuigia , Clement Bernd , Di Stefano Antonio , Amoroso Rosa
Published: August 2020

Under different pathological conditions, aberrant induction of neuronal nitric oxide synthase (nNOS) generates overproduction of NO that can cause irreversible cell damage. The aim of this study was to develop an amidoxime prodrug of a potent nNOS inhibitor, the benzhydryl acetamidine. We synthesized the benzhydryl acetamidoxime, which was evaluated in vitro to ascertain the potential NOS inhibitory activity, as well as conducting bioconversion into the parent acetamidine. The prodrug was also profiled for in vitro physicochemical properties, by determining the lipophilicity, passive permeation through the human gastrointestinal tract and across the blood‐brain barrier by PAMPA, and chemical, enzymatic, and plasma stability. The obtained data demonstrate that the amidoxime prodrug shows an improved pharmacokinetic profile with respect to the acetamidine nNOS inhibitor, thus suggesting that it could be a promising lead compound to treat all those pathological conditions in which nNOS activity is dysregulated.
Changes in chronic medication adherence, costs, and health care use after a cancer diagnosis among low‐income patients and the role of patient‐centered medical homes
Authors: Spees Lisa P. , Wheeler Stephanie B. , Zhou Xi , Amin Krutika B. , Baggett Christopher D. , Lund Jennifer L. , Urick Benjamin Y. , Farley Joel F. , Reeder‐Hayes Katherine E. , Trogdon Justin G.
Published: August 2020

Background

Approximately 40% of patients with cancer also have another chronic medical condition. Patient‐centered medical homes (PCMHs) have improved outcomes among patients with multiple chronic comorbidities. The authors first evaluated the impact of a cancer diagnosis on chronic medication adherence among patients with Medicaid coverage and, second, whether PCMHs influenced outcomes among patients with cancer.

Methods

Using linked 2004 to 2010 North Carolina cancer registry and claims data, the authors included Medicaid enrollees who were diagnosed with breast, colorectal, or lung cancer who had hyperlipidemia, hypertension, and/or diabetes mellitus. Using difference‐in‐difference methods, the authors examined adherence to chronic disease medications as measured by the change in the percentage of days covered over time among patients with and without cancer. The authors then further evaluated whether PCMH enrollment modified the observed differences between those patients with and without cancer using a differences‐in‐differences‐in‐differences approach. The authors examined changes in health care expenditures and use as secondary outcomes.

Results

Patients newly diagnosed with cancer who had hyperlipidemia experienced a 7‐percentage point to 11‐percentage point decrease in the percentage of days covered compared with patients without cancer. Patients with cancer also experienced significant increases in medical expenditures and hospitalizations compared with noncancer controls. Changes in medication adherence over time between patients with and without cancer were not determined to be statistically significantly different by PCMH status. Some PCMH patients with cancer experienced smaller increases in expenditures (diabetes) and emergency department use (hyperlipidemia) but larger increases in their inpatient hospitalization rates (hypertension) compared with non‐PCMH patients with cancer relative to patients without cancer.

Conclusions

PCMHs were not found to be associated with improvements in chronic disease medication adherence, but were associated with lower costs and emergency department visits among some low‐income patients with cancer.
Ontogeny of the electric organ discharge and of the papillae of the electrocytes in the weakly electric fish Campylomormyrus rhynchophorus (Teleostei: Mormyridae)
Authors: Korniienko Yevheniia , Tiedemann Ralph , Vater Marianne , Kirschbaum Frank
Published: August 2020

The electric organ of the mormyrid weakly electric fish, Campylomormyrus rhynchophorus (Boulenger, 1898), undergoes changes in both the electric organ discharge (EOD) and the light and electron microscopic morphology as the fish mature from the juvenile to the adult form. Of particular interest was the appearance of papillae, surface specializations of the uninnervated anterior face of the electrocyte, which have been hypothesized to increase the duration of the EOD. In a 24.5 mm long juvenile the adult electric organ (EO) was not yet functional, and the electrocytes lacked papillae. A 40 mm long juvenile, which produced a short biphasic EOD of 1.3 ms duration, shows small papillae (average area 136 μm2). In contrast, the EOD of a 79 mm long juvenile was triphasic. The large increase in duration of the EOD to 23.2 ms was accompanied by a small change in size of the papillae (average area 159 μm2). Similarly, a 150 mm long adult produced a triphasic EOD of comparable duration to the younger stage (24.7 ms) but featured a prominent increase in size of the papillae (average area 402 μm2). Thus, there was no linear correlation between EOD duration and papillary size. The most prominent ultrastructural change was at the level of the myofilaments, which regularly extended into the papillae, only in the oldest specimen—probably serving a supporting function. Physiological mechanisms, like gene expression levels, as demonstrated in some Campylomormyrus species, might be more important concerning the duration of the EOD.
Administration of 5‐bromo‐2′‐deoxyuridine interferes with neuroblast proliferation and promotes apoptotic cell death in the rat cerebellar neuroepithelium
Authors: Rodríguez‐Vázquez Lucía , Martí Joaquín
Published: August 2020

The current study was conducted to assess whether a single administration of 5‐bromo‐2′‐deoxyuridine (BrdU) interferes with cell proliferation and leads to the activation of apoptotic cellular events in the prenatal cerebellum. BrdU effects across a wide range of doses (25–300 μg/g b.w.) were analyzed using immunohistochemical and ultrastructural procedures. The pregnant rats were injected with BrdU at embryonic day 13, and their fetuses were sacrificed from 5 to 35 hr after exposure. The quantification of several parameters such as the density of mitotic figures, and BrdU and proliferating cell nuclear antigen (PCNA)‐reactive cells showed that, in comparison with the saline injected rats, the administration of BrdU impairs the proliferative behavior of neuroepithelial cells. The above‐mentioned parameters were significantly reduced in rats injected with 100 μg/g b.w. of BrdU. The reduction was more evident using 200 μg/g b.w. The most severe effects were found with 300 μg/g b.w. of BrdU. The present findings also revealed that high doses of BrdU lead to the activation of apoptotic cellular events as evidenced by both terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) assay and immunohistochemistry for active caspase‐3. In comparison with saline rats, many apoptotic cells were found in rats injected with 100 μg/g b.w. of BrdU. The number of dying cells increased with 200 μg/g b.w. The most important number of apoptotic cells were observed in animals injected with 300 μg/g b.w. of BrdU. Ultrastructural studies confirmed the presence of neuroblasts at different stages of apoptosis.
Dendritic spine abnormalities correlate with behavioral and cognitive deficits in mouse models of Lafora disease
Authors: Taneja Komal , Ganesh Subramaniam
Published: August 2020

Lafora disease (LD) is a genetic and fatal form of neurodegenerative disorder characterized by myoclonic epilepsy and cognitive deficits. LD is caused by loss‐of‐function mutations in the EPM2A or the NHLRC1 gene. A major hallmark of LD is the presence of abnormal glycogen aggregates in neurons and other tissues. Functional studies on the genes have, therefore, mostly focused on glycogen metabolism. The physiological basis of cognitive deficits in LD is thus largely unexplored. Alterations in dendritic spine morphology are known in neurodevelopmental and neuropsychiatric disorders. We, therefore, analyzed the dendritic spine morphologies in pyramidal neurons of the hippocampal and Cortical layer V of the Epm2a or Nhlrc1 knockout mice brain. We found a significant increase in the density, length, and reduction in the width of the dendritic spines in Postnatal day 21 to 12‐month‐old LD animals. Similar observations were made in the primary cultures of neurons derived from the hippocampi of the embryonic brain, suggesting that the aberrant spine phenotype could be a developmental defect in LD. We also looked at the cognitive and behavioral deficits as a possible readout of the spine abnormalities. The LD animals exhibited hyperactivity, reduced anxiety‐like behavior, and deficits in the spatial and nonspatial memory. Such abnormalities were seen in the younger (1–2 months) as well as the older (7–8 months) age groups. Taken together, our results suggest that the dendritic spine abnormalities are primary developmental defects in the LD model and these defects might underlie some of the symptoms, including cognitive deficits, in LD.
Performance prediction for distributed graph computing
Authors: Ji Shuo , Zhao Yinliang , Li Yuxiang
Published: August 2020

Performance prediction for executing graph applications on distributed systems is a prerequisite to improve system performance. Especially for distributed systems optimized by sacrificing the accuracy of results to improve runtime performance, performance prediction can be used to determine accuracy‐related system parameters to achieve a tradeoff between the runtime and inaccuracy of results. This article presents an approach that predicts the runtime and inaccuracy of executing graph algorithms on bulk synchronous parallel (BSP)‐based systems to optimize system parameters by using an artificial neural network (ANN). The proposed approach samples different scales of subgraphs from the input graph by maintaining that the features of subgraphs are similar to the features of the input graph. Then it executes graph algorithm on each subgraph and extracts their runtime features. An ANN‐based performance prediction model is trained off‐line based on the extracted features and is used to predict the performance of executing graph algorithm on the complete input graph. We have validated the proposed approach by conducting single‐source shortest path, connected component, and PageRank on the BSP‐based distributed systems. The experimental results demonstrate that the prediction method can effectively predict the runtime and the inaccuracy with a relative error rate under 14% and under 25%, respectively, compared with the actual performance results.
Constitutionally Isomeric Aromatic Tripeptides: Self‐Assembly and Metal‐Ion‐Modulated Transformations
Authors: Singh Narendra , Singh Ramesh , Joshi Khashti Ballabh , Verma Sandeep
Published: August 2020

Self‐assembling peptides based on aromatic amino acids can adopt diverse nanostructures which primarily depend on their molecular structures. Therefore, to understand the nature of self‐assembly on the molecular level we rationally designed two constitutional isomers of short aromatic peptides. The first isomer consists of a tyrosine moiety at the N‐terminus and the second isomer consists of a tyrosine moiety at the C‐terminus of the FF peptide, a core recognition motif of Amyloid β peptides. Therefore, it can be considered that both the designed tripeptides are the analogues of the FFF peptide with only atomic(−H) level replacement by −OH functional group on the first and last phenyl ring, respectively. The first isomer self‐assembled into 2D porous nanosheets (“Nanowebs”), however the second isomers produced toroidal shapes with central spheres (“Nano‐Saturn” like assemblies). Interestingly, the presence of the transition‐metal ions (copper, zinc and iron) triggered the self‐assembly of both the peptides into fibrous circular discs, nanomats and nanoplates like assembly.
Measuring Changes in Keap1‐Nrf2 Protein Complex Conformation in Individual Cells by FLIM‐FRET
Authors: Dikovskaya Dina , Dinkova‐Kostova Albena T.
Published: August 2020

The nuclear factor−erythroid 2 p45‐related factor 2 (Nrf2)−mediated stress response is a major cellular defense mechanism against endogenous and exogenous oxidants, electrophiles, and pro‐inflammatory agents. A number of Nrf2 inducers are being developed to therapeutically stimulate this pathway. Inducers are typically sensed by Kelch‐like ECH‐associated protein 1 (Keap1), a negative regulator and a binding partner of Nrf2. Modifications of Keap1 by oxidants or electrophiles, or its targeting by compounds that disrupt its interaction with Nrf2, alter the conformation of the Keap1‐Nrf2 protein complex, which initiates the accumulation of Nrf2 required for mounting a stress response. To detect conformational changes in the Keap1‐Nrf2 complex in live cells, we have developed a procedure based on Fluorescence Lifetime Imaging−Förster Resonance Energy Transfer (FLIM‐FRET). The procedure includes a FLIM time course in cells expressing fluorescently‐tagged Nrf2 and Keap1, followed by an extended analysis pipeline that quantifies changes in fluorescence lifetime of labeled Nrf2. The analysis visualizes and removes intensity‐dependent bias in fluorescence lifetime measured with the Time‐Correlated Single Photon Counting (TCSPC) approach, thereby improving the accuracy of quantification. The throughput is increased by the whole‐experiment analysis within the newly developed FLIM dataset tool (FLIMDAST) and by the time‐lapse FLIM described here. This pipeline is also suitable for applications beyond the Nrf2 field that assess small changes in fluorescence lifetime of objects with variable fluorescence intensities measured using TCSPC‐based FLIM. © 2020 The Authors.

Basic Protocol 1: Lipofectamine 2000 transfection

Alternate Protocol 1: Calcium phosphate transfection

Basic Protocol 2: Time course with individual FLIM

Alternate Protocol 2: Time course with time‐lapse FLIM

Support Protocol: Measuring Instrument Response Function (IRF)

Basic Protocol 3: Data analysis in SPCImage

Basic Protocol 4: Data processing in ImageJ/FIJI

Basic Protocol 5: Experiment analysis in FLIMDAST
Comparison of discriminatory effects of corn yield test locations based on their genetic variation expression among hybrids
Authors: Ashworth Amanda J. , Knapp Victoria , Allen Fred L. , Saxton Arnold M.
Published: August 2020

It is important for yield test sites to elicit differences among genotypes, minimize redundancy of performance information, and generate a genotype × environment interaction representative of the targeted region. The objective of this study was to use corn (Zea mays L.) variety trial data from three relative maturity group (MG) tests (early, medium, and late) at five Tennessee locations spanning 14 yr to compare test location uniqueness and redundancy via genetic variance estimates and cluster analysis. Principle component analyses allowed for location comparisons of genetic variance expression among cultivars in different MG tests. Individual location–test–year genetic variance estimates ranged from <1 to 584 (Mg ha−1)2. Years and locations affected the magnitude of genetic variance, with years largely driving genetic expression within MGs in these environments. However, the late MG consistently had the greatest variance estimates. Across 14 yr, there was minimum duplicative information provided across the five yield test sites. Consequently, all locations were needed and none could be eliminated without compromising cultivar yield trial information for the three MG tests. Correlations between mean yields and genetic variance showed a weak relationship across locations (environments), years, and MG tests (r = .021); thus, high‐yielding environments did not correspond with increased genetic variance expression. These types of analyses are useful for evaluating the discriminating ability and duplicative or correlated expression of genetic information across locations for robust variety trials within and across maturity groups and targeted regions.
Low temperature coefficient and low line sensitivity subthreshold curvature‐compensated voltage reference
Authors: Thakur Arvind , Pandey Rishikesh , Rai Shireesh Kumar
Published: August 2020

A high‐order curvature‐compensated subthreshold voltage reference is proposed in this paper. The proposed curvature‐compensated voltage reference consists of two supply‐independent first‐order voltage references and a curvature compensation circuit. The supply‐independent first‐order voltage reference uses a negative feedback loop which improves the line sensitivity and eliminates the demand of operational amplifier, whereas the curvature compensation circuit provides high‐order temperature‐compensated output reference voltage. The proposed curvature‐compensated voltage reference provides an output reference voltage of 118.54 mV with a temperature coefficient of 21.5 ppm/°C over a wide temperature range of −60°C to 120°C. The power supply rejection ratio and line sensitivity are observed as −68.64 dB (for the frequency range of 1 Hz to 100 Hz) and 0.035%/V (for the supply voltage varies from 0.85 V to 2.5 V), respectively. The values of output noise at the frequencies of 1 kHz and 10 kHz without using any capacitive filter are obtained as 179.13 nV/ √ Hz and 123.87 nV/ √ Hz, respectively.
A novel series of substituted 1,2,3‐triazoles as cancer stem cell inhibitors: Synthesis and biological evaluation
Authors: Padhariya Komal N. , Athavale Maithili , Srivastava Sangeeta , Kharkar Prashant S.
Published: August 2020

An alarming increase in global death toll resulting from cancer incidents, particularly due to multidrug resistance and reduced efficacy as a consequence of target mutations, has compelled us to look for novel anticancer agents. Cancer stem cells (CSCs), contributing majorly to the chemoresistance and tumor relapse, seem to the main culprits. In the present investigation, new chemical entities (NCEs) belonging to four novel chemical series (A: 4′‐allyl‐2′‐methoxyphenoxymethyl‐1,2,3‐triazoles; B: 4′‐acetamidophenoxymethyl‐1,2,3‐triazoles; C: naphthalene‐1′‐yloxymethyl‐1,2,3‐triazoles, and D: naphthalene‐2′‐yloxymethyl‐1,2,3‐triazoles) were synthesized via Copper (I)‐catalyzed alkyne‐azide cycloaddition reaction and evaluated for in vitro anticancer activity. A total of 30 NCEs (39–68) were screened at 10 μM concentration in cell viability assay against cancer cell lines such as breast (MDA‐MB‐231), prostate (PC‐3), glioma (U87 MG), along with cervical (SiHa) and lung (A549). The NCEs from Series C (56–60) and D (61–68) were more potent than those in Series A (39‐45) and Series B (46–55) at the tested concentration. Furthermore, NCEs with >80% inhibition at 10 μM were evaluated for dose response. A total of five NCEs, 48, 56, 61, 65 and 66, were further assessed in soft‐agar assay and found to be relatively potent (IC50 < 10 μM). Finally, the hits were screened in sphere assay to identify potential CSC inhibitors against mammospheres (MDA‐MB‐231) and prostatospheres (PC‐3). More so, the hits were also evaluated to understand in vitro cytotoxicity against normal cells using mouse embryonic fibroblast cell line (NIH/3T3) and human peripheral blood mononuclear cells (hPBMCs). Overall, hits 56 and 61 exhibited potent anticancer as well as CSC inhibitory activities with notably less toxicity toward NIH/3T3 and hPBMCs. On the whole, our arduous study led to the identification of potential hits with anticancer and CSC inhibitory activities, with minimal or no toxicity to normal cells.
Amino acid conjugates of 2‐mercaptobenzimidazole provide better anti‐inflammatory pharmacology and improved toxicity profile
Authors: Khan Muhammad T. , Nadeem Humaira , Khan Arif‐ullah , Abbas Muzaffar , Arif Muazzam , Malik Nadia Shamshad , Malik Zulkifal , Javed Ibrahim
Published: August 2020

Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti‐inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2‐mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti‐inflammatory and gastro‐protective effects. The synthesized 2‐mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2‐mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti‐inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti‐ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX‐2 (PDB ID: 3LN1) and H+/K+‐ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2‐mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
Are fission–fusion dynamics consistent among populations? A large‐scale study with Cape buffalo
Authors: Wielgus Elodie , Cornélis Daniel , de Garine‐Wichatitsky Michel , Cain Bradley , Fritz Hervé , Miguel Eve , Valls‐Fox Hugo , Caron Alexandre , Chamaillé‐Jammes Simon
Published: August 2020

Fission–fusion dynamics allow animals to manage costs and benefits of group living by adjusting group size. The degree of intraspecific variation in fission–fusion dynamics across the geographical range is poorly known. During 2008–2016, 38 adult female Cape buffalo were equipped with GPS collars in three populations located in different protected areas (Gonarezhou National Park and Hwange National Park, Zimbabwe; Kruger National Park, South Africa) to investigate the patterns and environmental drivers of fission–fusion dynamics among populations. We estimated home range overlap and fission and fusion events between Cape buffalo dyads. We investigated the temporal dynamics of both events at daily and seasonal scales and examined the influence of habitat and distance to water on event location. Fission–fusion dynamics were generally consistent across populations: Fission and fusion periods lasted on average between less than one day and three days. However, we found seasonal differences in the underlying patterns of fission and fusion, which point out the likely influence of resource availability and distribution in time on group dynamics: During the wet season, Cape buffalo split and associated more frequently and were in the same or in a different subgroup for shorter periods. Cape buffalo subgroups were more likely to merge than to split in open areas located near water, but overall vegetation and distance to water were very poor predictors of where fission and fusion events occurred. This study is one of the first to quantify fission–fusion dynamics in a single species across several populations with a common methodology, thus robustly questioning the behavioral flexibility of fission–fusion dynamics among environments.
Pasture management, grazing, and fire interact to determine wetland provisioning in a subtropical agroecosystem
Authors: Sonnier Grégory , Quintana‐Ascencio Pedro F. , Bohlen Patrick J. , Fauth John E. , Jenkins David G. , Boughton Elizabeth H.
Published: August 2020

Wetlands in agroecosystems provide multiple ecosystem services, including provisioning services such as forage production. Here, we examine how pasture management intensity (semi‐natural pastures vs. highly managed pastures (fertilized, heavily drained, planted with productive grasses), cattle exclusion (grazed vs. fenced), prescribed fire (burned vs. unburned), and their interactions affect provisioning services provided by small, isolated, and seasonally flooded wetlands in subtropical pastures and rangelands. We used a replicated, full‐factorial experiment on 40 seasonally flooded wetlands located in Florida (USA), and measured standing plant biomass and annual net primary productivity in each wetland. Biomass was sorted by species to calculate species abundance of palatable and unpalatable plants. We used general linear mixed models to evaluate the effect of treatments and their interactions on biomass quantity, plant tissue nutrients (% C, % N, and % P), and forage nutritive value (using in vitro organic matter digestibility). Plant standing biomass and productivity were greatest in wetlands embedded in highly managed pastures, but in grazed wetlands, a large proportion of this biomass was unpalatable to cattle. Excluding cattle from wetlands in highly managed pastures increased productivity, standing biomass, and the amount of palatable species (~6.3 t/ha) compared to grazed wetlands (~3.3 t/ha), especially when these wetlands were also exposed to prescribed fire. Total P in plant tissue was consistently higher in wetlands within highly managed pastures, but total N responses to treatments varied between years. In vitro digestibility was higher in vegetation from wetlands within highly managed pastures, but not in fenced wetlands despite the higher amount of palatable species, suggesting that palatability and digestibility were decoupled. Subtropical wetlands in agroecosystems provide substantial provisioning services, and our study suggests that targeted management can increase these services. However, the pasture type surrounding a wetland interacts with grazing and fire management to affect provisioning services. We propose that fencing off selected wetlands (specifically in highly managed pastures) followed by low‐intensity grazing with adequate resting periods could benefit ranchers and have less persistent impacts on this ecosystem.
Management of remnant tallgrass prairie by grazing or fire: effects on plant communities and soil properties
Authors: Larson Diane L. , Hernández Daniel L. , Larson Jennifer L. , Leone Julia B. , Pennarola Nora
Published: August 2020

Tallgrass prairie is a disturbance‐dependent ecosystem that has suffered steep declines in the midwestern United States. The necessity of disturbance, typically fire or grazing, presents challenges to managers who must apply them on increasingly small and fragmented parcels. The goal of this study was to compare effects of management using cattle grazing or fire on vegetation and soil characteristics to aid managers in making decisions regarding the kind of disturbance to apply. We selected 73 sites, of which 27 were managed solely by cattle grazing and 46 solely by fire, for at least 11 yr leading up to the study. We stratified the sites by prairie type (dry, mesic, and wet) and sampled frequency of plant species on randomly placed transects, supplemented with botanist‐directed walks, and collected and composited five soil cores on a randomly selected transect within each prairie type at each site. We calculated rarefied richness and Shannon evenness from the transect data and mean coefficient of conservatism (CofC) from the total list of species. Soil samples were analyzed for texture, bulk density, total N and C, and potential net N nitrification and mineralization. A nonmetric multidimensional scaling analysis of the plant community data revealed differences in species associated with mesic and wet prairies, but no separation by management type. Similarly, none of the vegetation variables we calculated varied by management type, as determined by mixed‐effects models, but soil bulk density was 17.5% higher and total N was 22% higher on grazed sites than burned sites. Sites burned more recently had higher species richness and mean CofC, but fire was not associated with any soil variables. Sites grazed more recently had higher bulk density, total N and C, and faster N cycling rates. Overall, 28% of plant species were found exclusively in one management type or the other, but these species did not vary in mean CofC. We conclude that, at the levels of burning and grazing intensity we studied, both management approaches produce similar C storage and vegetation responses. To maintain maximum diversity across the landscape, however, both approaches are necessary.
Synthesis of lithium manganese oxide nanocomposites using microwave‐assisted chemical precipitation technique and their performance evaluation in lithium‐ion batteries
Authors: Tariq Hanan Abdurehman , Abraham Jeffin James , Shakoor Rana Abdul , Al‐Qaradawi Siham , Abdul Karim Muhammad Ramzan , Chaudhry Usman
Published: August 2020

Lithium manganese oxide (LMO), carbon nanotubes (CNTs), and graphene nanoplatelets (GNPs) were used to develop nanocomposites using a microwave‐assisted chemical precipitation method and characterized using various techniques. The process provides better control over morphological features and proficient choice of cost‐effective precursors. This research aims to increase the active surface area and the number of lithium‐ion (Li+) intercalation sites using the CNTs and GNPs in LMO to improve its electrochemical performance. The structural analysis shows that the average crystallite size is 50 nm without using any capping agent during the synthesis process, which is smaller when compared to pristine LMO. The electrochemical studies demonstrate that the incorporation of carbon nanostructures (CNTs and GNPs) boosts the rate capabilities and cyclic performance of LMO. The LMO‐CNTs and LMO‐GNPs have an excellent rate capability of 124 and 127 mAhg−1 at 0.1C, sustained at 115.6 and 118.5 mAhg−1 at 10C, respectively. Cycling efficiency is also improved, with LMO‐CNTs and LMO‐GNPs having an initial capacity of 124 and 127 mAhg−1 decreasing to 112 and 114 mAhg−1, respectively, after 50 cycles. Compared to pure LMO, the increased electrochemical performance of LMO nanocomposites is due to the introduction of carbon nanostructures (CNTs and GNPs).
Cuckoo inspired stacking ensemble framework for content‐based cybercrime detection in online social networks
Authors: Singh Amanpreet , Kaur Maninder
Published: August 2020

In recent times, the topic of content‐based cybercrime has gained significant attention. It is the requirement of today's era for social media companies to meet the challenges faced in differentiating the oppressive content in both a precise and proficient manner, thereby securing their clients. This article proposes a novel cuckoo inspired stacking ensemble framework that is the integration of Cuckoo Search and several machine learning models. The proposed framework automatically seeks for near‐optimal combinations of classification techniques along with their tuning parameters for efficiently solving the problem of content‐based cybercrime detection. Four datasets obtained from Formspring, ASKfm, and Twitter are used for testing purposes. The experimental results showcased significant improvement in the performance of classification on all the datasets in comparison to state‐of‐art classification models. The success rate of the proposed model with the excellent recall is 0.984 via 10‐fold cross‐validation demonstrates its high efficiency and effectiveness.
Low‐overhead inline deduplication for persistent memory
Authors: Chen Wande , Chen Zhenke , Li Dingding , Liu Hai , Tang Yong
Published: August 2020

Persistent memory (PM) can play an important role in storing the edge data of IoT devices, but their capacities are restrained by the embedded system, which only provides the limited host space and energy resource. Therefore, a deduplication system is required to improve the PM utilization and energy consumption. According to our observations, the current inline deduplication algorithms incur nonnegligible latency when applied to the PM file systems (PMFSs), mainly because (i) the low tolerance to the extra deduplication I/O path, (ii) the long fingerprint calculation, and (iii) the unnecessary duplication detection when writing content with low duplication ratio. To improve this issue, we propose LO‐Dedup, a novel and low‐overhead deduplication system for PM. LO‐Dedup adopts PM‐friendly design, both in fine‐grained data load/store and fast hash scheme to reduce overhead. Moreover, LO‐Dedup can adaptively sample duplication detection according to the recent contents. We implement a prototype of LO‐Dedup in PMFS, which is a well‐known PMFS. The experimental results show that the write performance only has a slight drop when writing data and saves up to 45% space in PMFS.
Direct cortical thickness estimation using deep learning‐based anatomy segmentation and cortex parcellation
Authors: Rebsamen Michael , Rummel Christian , Reyes Mauricio , Wiest Roland , McKinley Richard
Published: August 2020

Accurate and reliable measures of cortical thickness from magnetic resonance imaging are an important biomarker to study neurodegenerative and neurological disorders. Diffeomorphic registration‐based cortical thickness (DiReCT) is a known technique to derive such measures from non‐surface‐based volumetric tissue maps. ANTs provides an open‐source method for estimating cortical thickness, derived by applying DiReCT to an atlas‐based segmentation. In this paper, we propose DL+DiReCT, a method using high‐quality deep learning‐based neuroanatomy segmentations followed by DiReCT, yielding accurate and reliable cortical thickness measures in a short time. We evaluate the methods on two independent datasets and compare the results against surface‐based measures from FreeSurfer. Good correlation of DL+DiReCT with FreeSurfer was observed (r = .887) for global mean cortical thickness compared to ANTs versus FreeSurfer (r = .608). Experiments suggest that both DiReCT‐based methods had higher sensitivity to changes in cortical thickness than Freesurfer. However, while ANTs showed low scan‐rescan robustness, DL+DiReCT showed similar robustness to Freesurfer. Effect‐sizes for group‐wise differences of healthy controls compared to individuals with dementia were highest with the deep learning‐based segmentation. DL+DiReCT is a promising combination of a deep learning‐based method with a traditional registration technique to detect subtle changes in cortical thickness.
CFD analysis on heat transfer through different extended surfaces
Authors: Sahoo Laxman K. , Roul Manmatha K.
Published: August 2020

The present study includes computational fluid dynamics analysis and comparison of heat enhancement through different extended surfaces, especially in rectangular and square conductive and nonconductive fins. Computational and numerical analysis of heat transfer from a rectangular extended surface and a pin‐finned plate studied to calculate the average Nusselt number in parallel, vertical direction placed along the sidewall. The total rise of the mean Nusselt number is noticed around 36% in pin‐finned plate with respect to a plain plate. This is examined with optimal fin spacing of Sv with L ratio equals to 0.2 and Sh with W ratio equals to 0.25, height of extended surfaces 24 mm with 45° angle of inclination. The mean Nusselt number reduces with a rise in the angle of inclination and also increases with a rise in aspect ratio. The present study reveals that inline and staggered arrangements do not yield appreciably different results. The maximum average Nusselt number difference between conductive and nonconductive fins is around 5% for Sh per W ratio 0.33 and Sv per L ratio 0.2 at an angle of inclination 45°, fin height of 6 mm (height to thickness ratio 2).