bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiscale Formation Damage Mechanisms and Control Technology for Deep Tight Clastic Gas Reservoirs
Authors: Wang Yijun , Kang Yili , You Lijun , Xu Chengyuan , Yan Xiaopeng , Lin Chong
Published: May 2021

Severe formation damage often occurs during the drilling process, which significantly impedes the timely discovery, accurate evaluation, and efficient development of deep tight clastic gas reservoirs. The addition of formation protection additives into drilling fluid after diagnosing the damage mechanism is the most popular technique for formation damage control (FDC). However, the implementation of traditional FDC measures does not consider the multiscale damage characteristics of the reservoir. The present study aims at filling this gap by providing a complete and systematic damage control methodology based on multiscale FDC theory. First, the characteristics of multiscale seepage channels were described through petrology, petrophysics, and well-history data. Subsequently, based on laboratory formation damage evaluation experiments, the formation damage mechanism of each seepage scale was determined. Finally, based on the multiscale formation damage mechanism, a systematic multiscale FDC technology was proposed. Through the use of optimized drilling fluid based on multiscale FDC theory, high-permeability recovery ratio (PRR), high-pressure bearing capacity of plugging zone, and low cumulative filtration loss were observed by laboratory validation experiments. Shorter drilling cycle, less drill-in-fluid loss, lower skin factor, and higher production rates were obtained by using the optimized FDC drilling fluid in field application. This multiscale FDC theory shows excellent results in minimizing formation damage, maintaining original production capacity, and effectively developing gas reservoirs with multiscale pore structure characteristics.
Progression of Corneal Endothelial Insult by Chronic Elevation of intraocular Pressure: A prospective Observational Comparative Study Among Primary Open Angle Glaucoma Patients
Authors: A.Mateen Elshimaa , Ammar Hatem Gamal , Sayed Khulood Muhammad
Published: May 2021

Purpose: To evaluate specular microscopic changes of corneal endothelial cells (CEC) count and morphology in correlation to retinal nerve fiber layer RNFL changes detected by visual field (VF) and OCT in early and advanced primary open-angle glaucoma (POAG).Methods: A prospective observational comparative study was conducted on patients with POAG versus non-glaucomatous patients of the same age group. Specular microscopy, VF test, OCT scans of RNFL, and macular ganglion cell complex (GCC) were performed. Glaucoma group was further subdivided into early and advanced stages.Results: The study included 130 eyes of 130 subjects, 70 were eyes with POAG (glaucoma group), 60 were healthy eyes (control group). Both groups were comparable regarding mean age and sex.In the early glaucoma group, a significant negative correlation was found between the coefficient of variation (CV%) and superior PRNFL thickness (r=-0.5, p-value=0.018). A significant negative correlation was also found between percentage of cellular hexagonality (HEX%) and vertical cup/disc (C/D) ratio (r=-0.43, p-value= 0.035). A significant positive correlation was found between HEX% and (superior, inferior) PRNFL thickness (r=0.53, 0.5 and p-value= 0.008, 0.015) respectively.Mean CEC count was significantly lower in the advanced glaucoma group than in the control group (2958.7±371.2 vs 3085±172.5, p value=0.043). Conclusions: CEC is affected by chronic intraocular pressure (IOP) elevation just like the PRNFL and macular GCC. CEC morphology is insulted in the early stages of POAG while the count can withstand chronic IOP elevation till advanced stages were both are affected.
Female Breast Cancer Trends in Disaggregated Asian American Populations: Analysis of 2003-2017 U.S. Mortality Data
Authors: Bhamidi Vaishnavi , Islas Nathaniel , Feng Caroline , Garg Naveli , Xi Kevin , Huang Robert , Au Timothy , Sharp Nora , Kurian Allison W. , Palaniappan Latha , Chung Sukyung , Thompson Caroline A. , Sriniva Malathi
Published: May 2021

PurposeBreast cancer is the second leading cause of female cancer mortality in the United States and breast cancer mortality in Asian Americans (AA) is rising by 1.5% per year. However, aggregated AA breast cancer death rates may mask important mortality differences in major AA groups.Population & Setting11,388 AA and 473,927 non-Hispanic White (NHW) females based on the United States Centers for Disease Control and Prevention National Vital Statistics System database 2003-2017.MethodsAge-adjusted mortality rates (AAMR) were used to estimate trends in breast cancer mortality in Asian Indians, Chinese, Filipinas, Japanese, Koreans, Vietnamese, and non-Hispanic Whites from 2003–2017, with attention to annual percentage change (APC) and proportional mortality rates (PMR).ResultsFrom 2003-2017, breast cancer deaths comprised 14.4% in NHWs, 13.7% in aggregate AAs, 19.8% in Asian Indians, and 18.6% of all cancer deaths in Filipinas. While NHW breast cancer mortality rate significantly decreased (APC -2.1; CI -2.6, -1.6; p < 0.001) from 2003 to 2017, aggregate AA mortality rates were unchanged (APC 3.07; CI -0.37, 7.8; p = 0.071). However, when disaggregated, breast cancer mortality in Filipina (APC 1.9; CI 0.8, 3.0; p < 0.002), Chinese (APC 2.1; CI 1.3, 3.0; p < 0.001), and Korean (APC 2.6; CI 1.0, 4.1; p = 0.004) women significantly increased. Breast cancer mortality rates in Japanese women decreased (APC -1.9; CI -5.9, 2.1; p = 0.3).ConclusionWhile the proportion of women dying from breast cancer were similar in NHWs and aggregate Asians, when disaggregated, Filipina, Korean, and Chinese women had increased mortality rates over the past 15 years. During this time, breast cancer mortality in NHW and Japanese women decreased. Understanding disaggregated breast cancer mortality rates in Asians may improve culturally-tailored outreach, prevention, and treatment strategies to reduce cancer deaths from this critical disease.
Slow slip events are regular earthquakes
Authors: Weng Huihui
Published: May 2021

Slow slip events usually occur downdip of seismogenic zones in subduction megathrusts and crustal faults, with rupture speeds much slower than earthquakes. The empirical moment-duration scaling relation can help constrain the physical mechanism of slow slip events, yet it is still debated whether this scaling is linear or cubic and a fundamental model unifying slow slip events and earthquakes is still lacking. Here I present numerical simulations that show that slow slip events are regular earthquakes with negligible dynamic-wave effects. A continuum of rupture speeds, from arbitrarily-slow speeds up to the S-wave speed, is primarily controlled by the stress drop and a transition slip rate above which the fault friction transitions from rate-weakening behaviour to rate-strengthening behaviour. This continuum includes tsunami earthquakes, whose rupture speeds are about one-third of the S-wave speed. These numerical simulation results are predicted by the three-dimensional theory of dynamic fracture mechanics of elongated ruptures. This fundamental model unifies slow slip events and earthquakes, reconciles the observed moment-duration scaling relations, and opens new avenues for understanding earthquakes through investigations of the kinematics and dynamics of frequently occurring slow slip events.
β-Hydroxybutyrate Exacerbates Hypoxic Injury by Inhibiting HIF-1α-Dependent Glycolysis in Cardiomyocytes—Adding Fuel to the Fire?
Authors: Ma Xiurui , Dong Zhen , Liu jingyi , Ma Leilei , Sun Xiaolei , Gao Rifeng , Pan Lihong , Zhang Jinyan , A Dilan , An Jian , Hu Kai , Sun Aijun , Ge Junbo
Published: May 2021

Purpose: Ketone body oxidation yields more ATP per mole of consumed oxygen than glucose. However, whether an increased ketone body supply in hypoxic cardiomyocytes and ischemic hearts is protective or not remains elusive. The goal of this study is to determine the effect of β-hydroxybutyrate (β-OHB), the main constituent of ketone bodies, on cardiomyocytes under hypoxic conditions and the effects of ketogenic diet (KD) on cardiac function in a myocardial infarction (MI) mouse model. Methods: Adult mouse cardiomyocytes and MI mouse models fed a KD were used to research the effect of β-OHB on cardiac damage. qPCR, western blot analysis and immunofluorescence were used to detect the interaction between β-OHB and glycolysis. Live/dead cell staining and imaging, lactate dehydrogenase, Cell Counting Kit-8 assays, echocardiography and 2,3,5-triphenyltetrazolium chloride staining were performed to evaluate the cardiomyocyte death, cardiac function and infarct sizes. Results: β-OHB level was significantly higher in acute MI patients and MI mice. Treatment with β-OHB exacerbated cardiomyocyte death and decreased glucose absorption and glycolysis under hypoxic conditions. These effects were partially ameliorated by inhibiting hypoxia-inducible factor 1α (HIF-1α) degradation via roxadustat administration in hypoxia-stimulated cardiomyocytes. Furthermore, β-OHB metabolisms were obscured in cardiomyocytes under hypoxic conditions. Additionally, MI mice fed a KD exhibited exacerbated cardiac dysfunction compared with control chow diet (CD)-fed MI mice. Conclusion: Elevated β-OHB levels may be maladaptive to the heart under hypoxic/ischemic conditions. Administration of roxadustat can partially reverse these harmful effects by stabilizing HIF-1α and inducing a metabolic shift toward glycolysis for energy production.
Soil Fungal Community Composition Is More Sensitive To Nitrogen And Phosphorus Additions Than The Bacterial Community In A Temperate Meadow Ecosystem
Authors: Yan Yan , Zhao Nanyi , Sun Fengwei , Sun Wei , Zhang Tao
Published: May 2021

Background and aims Soil microorganisms play key roles in the cyclings of soil nutrient and ecosystem stability, however, the soil microbial community composition often is influenced by nutrient enrichment. Increased nitrogen (N) input endangers plant species diversity and stability of grassland ecosystems, and which should be often affected by the addition of phosphorus (P) addition. However, the resistance of soil microbial community to N and P additions, and their interactions in the N-limited temperate meadow ecosystem remains poorly understood.Methods We carried out a seven-year experiment with the additions of N and P in a temperate meadow. The community structures of soil bacteria and fungi were examined based on high-throughput sequencing targeting the 16S rRNA and ITS genes, respectively.Results N addition did not influence on the community composition and species richness of bacteria, while altered soil fungal community composition and increased fungal OTU richness. P addition significantly altered soil fungal and bacterial community compositions and declined the richness of bacterial OTU, increased the OTU richness of fungi. The Proteobacteria (38.5%) and Acidobacteria (22.3%) were the most dominant bacteria. The Ascomycota was the dominant fungi (42.6%) across all samples. The enrichment of soil available P concentration caused by the addition of P played key roles in the bacterial β-diversity, while the β-diversity of soil fungi was mainly influenced by the concentrations of soil N and P, and soil moisture. Conclusions The sensitivity of soil fungi and bacteria to the addition of P is stronger than N addition, and which is more sensitive than the plant community. Our result highlights the unequal sensitivity of soil fungal and bacterial community composition and structure to the eutrophications of N and P, thereby causing changes in above and belowground communities and influencing ecosystem stability in the studied temperate meadow ecosystem.
Automation Assisted Anaerobic Phenotyping For Metabolic Engineering
Authors: Venkatesan Kaushik , Venayak Naveen , Diep Patrick , Golla Sai Akhil , Yakunin Alexander , Mahadevan Radhakrishnan
Published: May 2021

Background: Microorganisms can be metabolically engineered to produce a wide range of commercially important chemicals. Advancements in computational strategies for strain design and synthetic biological techniques to construct the designed strains have facilitated the generation of large libraries of potential candidates for chemical production. Consequently, there is a need for a high-throughput, laboratory scale techniques to characterize and screen these candidates to select strains for further investigation in large scale fermentation processes. Several small-scale fermentation techniques, in conjunction with laboratory automation have enhanced the throughput of enzyme and strain phenotyping experiments. However, such high throughput experimentation typically entails large operational costs and generate massive amounts of laboratory plastic waste. Results: In this work, we develop an eco-friendly automation work ow that effectively calibrates and decontaminates fixed-tip liquid handling systems to reduce tip waste. We also investigate inexpensive methods to establish anaerobic conditions in microplates for high-throughput anaerobic phenotyping. To validate our phenotyping platform, we perform two case studies - an anaerobic enzyme screen, and a microbial phenotypic screen. We used our automation platform to investigate conditions under which several strains of E. coli exhibit the same phenotypes in 0.5 L bioreactors and in our scaled-down fermentation platform. We also propose the use of dimensionality reduction through t-distributed stochastic neighbours embedding (t-SNE) in conjunction with our phenotyping platform to effectively cluster similarly performing strains at the bioreactor scale. Conclusions: Fixed-tip liquid handling systems can significantly reduce the amount of plastic waste generated in biological laboratories and our decontamination and calibration protocols could facilitate the widespread adoption of such systems. Further, the use of t-SNE in conjunction with our automation platform could serve as an effective scale-down model for bioreactor fermentations. Finally, by integrating an in-house data-analysis pipeline, we were able to accelerate the 'test' phase of the design-build-test-learn cycle of metabolic engineering.
Response of Leaf Biomass, Leaf and Soil C:N:P Stoichiometry Characteristics to Different Site Conditions and Forest Age: A Case of Pinus Tabuliformis Plantations in the Temperate Mountainous Area of China
Authors: Liu Ping , Wang Lijiao , Jing Xin , Yu Lei , Wang Yutao
Published: May 2021

Background: Ecological stoichiometry is an important index that reflects the element cycle and ecosystem stability. In this study, two sites (sunny and shady slopes) and five forest ages (young forest, middle-aged forest, near-mature forest, mature forest, and over-mature forest) in a Pinus tabuliformis plantation were chosen to illustrate the effects of forest age and site on the biomass and stoichiometric characteristics of leaves and soils in the temperate mountainous area of China. Results: For all forest ages, the biomass, leaf total carbon, leaf total nitrogen, leaf total phosphorus of the leaves of P. tabuliformis on sunny slopes were all higher than those on shady slopes, while the nitrogen and phosphorus contents of the leaves showed the opposite of this. The biomass of leaves increased on sunny slopes, and increased first and then decreased in shady slopes with increasing forest age. The contents of soil total carbon (STC) and soil total nitrogen (STN) decreased with increasing soil depth, while the soil total phosphorus (STP) and soil available phosphorus (SAP) contents displayed the opposite. In addition to SAP, the average content of STC, STN, and STP in shady slopes was higher than that in sunny slopes, and the ratio was the opposite. Except for STC:STN on shady slopes, the other ratios showed a downward trend with an increase in soil depth. Excluding the topsoil, the change trend of STC:STP and STN:STP in shady slopes and sunny slopes was consistent with forest age. Conclusions: The results showed that forest age and site conditions had significant effects on leaf biomass. The biomass of the leaves is mainly limited by nitrogen. In management, it is recommended to plant on sunny slopes, especially in the young stage of P. tabuliformis plantation. In addition, it is suggested to apply a reasonable amount of nitrogen fertilizer to increase leaf biomass.
Variability of Microbial Communities in Two Long-term Ice-covered Freshwater Lakes in the Subarctic Region of Yakutia, Russia
Authors: Zakharova Yulia Robertovna , Bashenkhaeva Maria Victorovna , Galachyants Yuri Pavlovich , Petrova Darya Petrovna , Tomberg Irina Victorovna , Marchenkov Artyom Mikhailovich , Kopyrina Liubov Innokentyevna , Likhoshway Yelena Valentinovna
Published: May 2021

Although under-ice microbial communities are subject to a cold environment, low concentrations of nutrients, and a lack of light, they nevertheless take an active part in biogeochemical cycles. However, we still lack an understanding of how high their diversity is and how these communities are distributed during the long-term ice-cover period. Here we assessed for the first time the composition and distribution of microbial communities during the ice-cover period in two subarctic lakes (Labynkyr and Vorota) located in the area of the lowest temperature in the Northern Hemisphere. The diversity distribution and abundance of main bacterial taxa, and the composition of microalgae, varied by time and habitat. The 16S rRNA gene sequencing method revealed, in general, a high diversity of bacterial communities where Proteobacteria (~59%) and Actinobacteria (~11%) prevailed. There were significant differences between the communities of the lakes: Chthoniobacteraceae, Moraxellaceae, and Pirellulaceae were abundant in Lake Labynkyr, while Cyanobacteria, Oligoflexales, Ilumatobacteraceae, and Methylacidiphilaceae were more abundant in Lake Vorota. The most abundant families were evenly distributed in April, May and June their contribution was different in different habitats. Moraxellaceae, Ilumatobacteraceae dominated in April in the water column, while Sphingomonadaceae dominated both in water column and on the ice bottom. In May, the number of Comamonadaceae increased and reached the maximum in June, while Cyanobacteria, Oxalobacteraceae and Pirellulaceae followed. We found a correlation of the structure of bacterial communities with snow thickness, рН, total nitrogen concentration, and conductivity. We isolated psychrophilic heterotrophic bacteria both from dominating and minor taxa of the communities studied. This allowed for specifying their ecological function in the under-ice communities. These findings will advance our knowledge of the under-ice microbial life.
Measuring Mental Wellness Among Adolescents Living With A Physical Chronic Condition: A Systematic Review of the Mental Health and Mental Wellbeing Instruments
Authors: Orth Zaida , Wyk Brian van
Published: May 2021

Background: Globally, promoting mental health and wellbeing among adolescents has become a public health priority, especially for adolescents living with a chronic condition (CC) as research suggests they may be more at risk of developing mental health co-morbidities. Valid and reliable instruments are needed to measure and better understand mental health and mental wellbeing among adolescents living with a CC. To this end, we reviewed studies reporting on mental health and well-being instruments used in adolescent populations living with a chronic physical condition/disease globally.Methods: We used a systematic review method guided by PRISMA to identify assess mental health and mental wellbeing instruments used in adolescents living with a CC. In this instance, mental health instruments were defined as those representing negative domains of mental health (i.e. depression and anxiety) while mental wellbeing instruments included positive aspects of mental health (i.e. self-concept and resilience). Results: We identified 22 articles, which include 31 instruments that were used to measure either mental health (n= 8) or mental wellbeing (n= 15) or both (n=8) in adolescents living with a CC. Of these, thirteen studies used a Health-Related Quality of Life (HRQoL) scale to measure mental health and/or mental well-being; and three studies used. The KIDSCREEN questionnaires and the Strengths and Difficulties Questionnaire were identified as being frequently used across the 22 studies. Additionally, 7 out of the 31 instruments were disease specific, with 3 focusing on adolescents with diabetes. All the instruments were developed in high income countries and adapted for use in lower- and middle-income countries (LMICs). Adolescents with Type 1 Diabetes (n=7) and HIV (n=4) were researched in 11 out of 22 studies. Only eight studies were conducted in LMIC, of which four were in Africa. Conclusions: The findings suggest that HRQoL instruments seem to be useful in measuring mental health - and wellbeing in adolescents living with a CC. Relatively few valid measures of mental health and mental wellbeing for adolescents living with a CC exist generally, which confirms the paucity of research on mental health and mental well-being of adolescents who are living with a CC. There is a need for measures to be developed in LMIC where cultural contexts differ greatly and affects well-being in unique ways.Systematic review registration: PROSPERO CRD42020186707
Effects of cranioplasty in cerebral blood perfusion using quantification with 99mTc-HMPAO SPECT-CT
Authors: Galiana Álvaro , Paredes Igor , Ruiz Sebastián , Alén José Antonio Fernández , Grande Adolfo Gómez , Panero Irene , Vega Diana , García Daniel , Gutiérrez Elena , Romero Carmen , Lagares Alfonso , Tabuenca María José
Published: May 2021

PURPOSE: SSFS is an underdiagnosed complication of craniectomized patients, which mainly presents with headache, motor weakness, and cognitive impairments. In these patients, cranioplasty improves these symptoms. Furthermore, patients without a classical SSFS have been shown to improve their neurological functions after reconstructive surgery. Amongst the many different pathophysiological theories proposed, the changes of CBP caused by the cranial defect might have a role in the neurological deficiencies. We have studied CBP in twelve cortical areas of both hemispheres, using 99mTc-HMPAO SPECT-CT before and after cranioplasty.METHODS: Twenty-eight craniectomized patients subject to reconstructive surgery were studied with 99mTc- HMPAO in three different times, before cranioplasty, a week after, and three months later. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area , and with a database of normal individuals. A mixed effects model was used to determine the signification of CBP changes in the cortex regions of both the damaged and undamaged brain hemispheres.RESULTS: CBP increased significantly in both hemispheres after cranioplasty both in ratio (β=0.019 p-value=0,030 first post-surgical SPECT-CT and β=0.021 p-value=0,015 in the second study, vs. pre-surgical) and Z-score (β=0.220 p-value=0,026 and β=0.279 p-value=0,005 respectively). Nine of twelve areas of the damaged side had a significant lower CBP ratio and Z-score than the undamaged. Posterior cingulate showed an increased CBP ratio (p-value=0,034) and Z-score(p-value0,028) in the first post-surgical SPECT-CT.CONCLUSION: CBP changes significantly in specific cortical areas after cranioplasty, which might explain the clinical improvements observed. Posterior cingulate changes might explain some improvements in attention impairments described. 99mTc-HMPAO SPECT-CT might be a valid tool to assess CBP changes in these patients and could have a role in the management of craniectomized individuals.CLINICAL TRIAL REGISTRATIONNot applicable
Overcoming the Technical Challenges of Total Knee Arthroplasty in Patients Affected by Hereditary Multiple Exostoses: Our Experience Managing the Bone Deformities
Authors: Cammisa Eugenio , Alesi Domenico , Meena Amit , Lullini Giada , Zaffagnini Stefano , Muccioli Giulio Maria Marcheggiani
Published: May 2021

Introduction: Hereditary multiple exostoses (MHE), also known as familiar osteochondromatosis or diaphyseal aclasis, is an autosomal dominant inherited genetic pathology that is characterized by the presence of multiple benign osteochondromas (exostoses). Knee deformity is common in patients with HME, with nearly a third of patients developing genu valgus. Total knee arthroplasty (TKA) has been used to correct valgus deformities with advanced knee osteoarthritis (OA). However concomitant limb deformities and altered anatomy of the knee make this surgery particularly challenging.Case presentation: We present the case of a 50 years old Caucasian woman, affected by multiple hereditary exostoses, who came to our attention for progressive pain in the right knee. Upon further examination the knee had a prominent valgus alignment, concomitant valgus instability and flexion contraction. The patient was treated with one stage total knee arthroplasty using a semi-constrained design. The patient was re-evaluated at 24 months follow-up and there were no signs of implant loosening, the knee function improved significantly and the patient was very satisfiedConclusions: We also present a mini-review of the literature on this topic. Given the recurring technical difficulties of such procedure in these patients, we describe our experience as well as the need for preoperative planning, the use of appropriate constrain when required, the high frequency of ligament instability, bony defects, and patellar maltracking. TKA must be considered when necessary, in these patients, as good to excellent clinical results can be achieved and maintained, allowing for significant improvements in quality of life.
Functional Traits on Cavity-nesting Birds in Subtropical Andean Forest: Response to Logging Activity and Comparing with American Temperate Forests
Authors: Schaaf Alejandro A. , Gomez Daniela , Tallei Ever , Vivanco Constanza G. , Ruggera Román A.
Published: May 2021

Logging causes changes in habitat structure, which can potentially lead to variations in taxonomic and functional richness of biodiversity. In this paper, we examined how logging in subtropical Andean forests has influenced taxonomic and functional diversity of cavity-nesting birds. We used point-counts to examine the effects of logging on taxonomic and functional traits of avian communities (Functional Richness, Functional evenness, Functional Divergence, and Community-weighted mean). We found that logging changes bird richness and abundance, although it had no effect on the functional response to the measured traits. The comparison of our results with those of temperate forests of Canada and Chile reveals differences in the functional richness, with a lower impact of logging on functional traits. We highlight the importance of including functional traits in the analyses, since the reduction in the species richness and abundance may not translate into functional changes within the ecosystem.
Role of Differentially Expressed Proteins in Acquired Resistance to Cdk4/6 Inhibitor in Breast Cancer
Authors: Kumar Binayak , Prasad Peeyush , Singh Ragini , Sahu Ram Krishana , Singh Ashutosh , M Srikrishna Jayadev , Hedau Suresh
Published: May 2021

CDK4/6 inhibitors (Abemaciclib, Ab and Palbociclib, Pb) stop the G1-phase in cell-cycle being used to cure advanced stage of breast cancer (BC). Acquired resistance is a major challenge in BC therapy. The molecular signature of the therapy resistance for Ab and Pb drugs in BC should be explored. Here, we developed Ab/Pb-resistant cell-models and explored the molecular changes. Drug’s resistance cells were developed in MCF-7 cells by continuous drug treatment and it was confirmed by MTT-assay, PI-staining-microscopy, and real-time-qPCR. Global proteome profiling done by Labelled-free-Proteome-Orbitrap-Fusion-MS-MS technique. Bioinformatics tools used to analyse the proteome data. Ab-resistant and Pb-resistant MCF-7 cells showed increased tolerance for the respective drug. The BCL-2 and MCL-1 survival genes were up-regulated, while the apoptosis genes BAD, BAX, CASP-3 and PARP-1were down-regulated in the resistant cells. Expression of the MDR-1, ABCG2, ESR-1, CDK4, CDK6, and Cyclin-D1 genes were increased in both resistance cells. For proteomics, 237 and 239 proteins were expressed differently in the resistant Ab and Pb cells, respectively. The NUDT5, PEPD, ABAT, ATP1B1, GGCT, and SELENBP1 proteins were down-regulated and the SBSN, HSD17B10, CD9, PDIA3, PSMB4, SLC2A1, and VTN proteins were up-regulated in Ab-resistant cells. The NUDT5, PEPD, and GGCT proteins were down-regulated, while CD47, HIST1H2BN, LMNA, VTN, PSMB5, HBB, PSMA7, FLNB, PRDX4, VDAC1, GOT2, HSPA5, SERPINH1, EIF4A2, FTH, and VIM proteins were up-regulated in Pb-resistant cells. These proteins are a new set of prognostic markers and drug targets for overcoming the respective drug resistance. However, it is necessary to perform an in vivo or clinical assessment.
A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism
Authors: Sheraj Ilir , Guray Tulin , Banerjee Sreeparna
Published: May 2021

Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.
Resolving sub-micrometer-scale zonation of trace elements in quartz using TOF-SIMS
Authors: North Ryan , Tanner Dominique , Nancarrow Mitchell , Pasic Bozana , Mavrogenes John A.
Published: May 2021

Quartz is abundant in the Earth’s continental crust and persistent throughout the geological record. Trace element signatures in silica minerals can be used to infer processes operating in magmatic and hydrothermal systems. Conventional analyses of trace elements in silica minerals are limited by either spatial or mass resolution [e.g., wavelength-dispersive X-ray spectroscopy, micro-X-ray fluorescence, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS)]. Time-of-flight SIMS (TOF-SIMS) is a relatively new technique for geological applications and provides both high spatial and mass resolution. This minimally destructive, in situ technique rapidly acquires a full suite of elements down to tens of nanometers depth. No previous study has utilized TOF-SIMS to analyze quartz or silica. Four samples of silica minerals representing distinct environments in a magmatic-hydrothermal system were characterized with optical microscopy and qualitative cathodoluminescence (CL), quantitatively analyzed for trace elements with a 157 nm LA-ICP-MS, and qualitatively mapped for trace elements using TOF-SIMS. The novel technique produced maps of trace element distribution in silica minerals to a maximum resolution of 65 nm and consistently resolved light elements (including Li) to 195 nm. That makes this study the highest resolution geochemical characterization of silica minerals and places it among the highest resolution analyses by TOF-SIMS, or any technique, for that matter. TOF-SIMS isotope maps differentiate trace elements hosted in nano- and micro-inclusions from lattice incorporation in quartz and cryptocrystalline silica—an impossibility for lower resolution techniques, allowing insights into cations substituting for Si4+ in the crystal lattice and their role in activating CL in low-temperature epithermal quartz. Further development of this technique could see TOF-SIMS become a routine tool for measuring diffusion profiles in a range of other geological materials. Quantification of TOF-SIMS would revolutionize mineral characterization, especially given its temporal efficiency and low-sampling volume.
Xuite, Ca3Fe2[(Al,Fe)O3(OH)]3, a new mineral of the garnet group: Implications for the wide occurrence of nanominerals
Authors: Lee Seungyeol , Guo Xiaofeng
Published: May 2021

Xuite, Ca3Fe2[(Al,Fe)O3(OH)]3, is a new member of the garnet supergroup discovered in basaltic scoria from Menan Volcanic Complex, Idaho, U.S.A. Oxidation of Fe-bearing pyroclasts at high temperatures led to the formation of xuite, together with luogufengite, valleyite, and hematite. The measured crystal size of xuite ranges from ~200 to 800 nm. The empirical chemical formula of xuite is (Ca0.92Mg0.08)3(Fe0.96Ti0.04)2[(AlO4H)0.44(FeO4H)0.33 (SiO4)0.05(☐O4H4)0.18]3. Xuite has a space group of Ia3d; its unit-cell parameter refined from high-resolution synchrotron X-ray diffraction (XRD) data is a = 12.5056(5) Å, with Z = 8 (calculated density = 3.53 g/cm3). Fourier-transform infrared spectroscopy spectrum of xuite shows absorption bands at 3682 and 3579 cm−1, indicating the presence of OH– in the hydrogarnet structure. In situ high-temperature synchrotron XRD combined with thermogravimetry and differential scanning calorimetry reveals that xuite undergoes dehydroxylation to form brownmillerite (Ca2FeAlO5) from ~236 to ~396 °C. Xuite occurs in the form of nanocrystals with a soft magnetic property, which provides important insights into the origin of basaltic scoria and associated paleomagnetism. Xuite was also found in Wyoming paralava, suggesting the possibility of its wide occurrence in various geological environments. The mineral was named after Huifang Xu and Hongwu Xu in honor of their sustained contributions to mineral sciences.
Euler-scale dynamical fluctuations in non-equilibrium interacting integrable systems
Authors: Perfetto Gabriele , Doyon Benjamin
Published: May 2021

We derive an exact formula for the scaled cumulant generating function of the time-integrated current associated to an arbitrary ballistically transported conserved charge. Our results rely on the Euler-scale description of interacting, many-body, integrable models out of equilibrium given by the generalized hydrodynamics, and on the large deviation theory. Crucially, our findings extend previous studies by accounting for inhomogeneous and dynamical initial states in interacting systems. We present exact expressions for the first three cumulants of the time-integrated current. Considering the non-interacting limit of our general expression for the scaled cumulant generating function, we further show that for the partitioning protocol initial state our result coincides with previous results of the literature.
Given the universality of the generalized hydrodynamics, the expression obtained for the scaled cumulant generating function is applicable to any interacting integrable model obeying the hydrodynamic equations, both classical and quantum.
Interrelatedness between Organizational Culture and Human Resource Management in the Context of Corporate Entrepreneurship
Authors: Naldi Syafri , Alexsander Dapit , Purnomo Margo
Published: May 2021

There has been numerous research carried out on corporate entrepreneurship. This term typically refers to organizational culture or human resource management (HRM). This article was written to supplement previous research that explored the link between entrepreneurship, the culture of organization, and HRM. The purpose of this study is to explain in several related articles the operationalization of the three principles and to explain the interrelationship between them in the context of corporate entrepreneurship. A systematic review process, namely an in-depth literature review of 25 search results articles based on certain keywords and limitations, was used in this research. The study produces a model that describes the influence of HRM on organizational culture or the impact of organizational culture on HRM, which can inspire businesses to adopt an approach to corporate entrepreneurship and enhance the efficiency of the company.
Estimating the Electrochemically Active Area: Revisiting a Basic Concept in Electrochemistry
Authors: Coelho Dyovani , Luiz Giuliana , Machado Sergio
Published: May 2021

The well-known electrochemical probe Fe(CN)63-/Fe(CN)64- is widely used for estimating the electrochemically active area of electrodes modified with carbon nanotubes, conductive polymers, enzymes, etc. In this study, we used the platinum electrode, smooth or platinized with different roughness factors, to demonstrate that such a redox couple fails to respond to a surface roughness variation. We determined the roughness factors of the Pt surfaces by atomic force microscopy (AFM) images, which yielded values between 2.72 and 25.91. Almost the same values were found by using the charge of the hydrogen monolayer desorption obtained from steady-state cyclic voltammetry experiments performed in an acid medium. They were then compared with those provided by peak current in voltammetry or chronoamperometry with Fe(CN)6 3-/Fe(CN)64- which all yielded values nearly to one. Such comparison demonstrates that the electrochemical behavior of the redox probe is an outer sphere reaction with a quite small interaction with the electrode surface, thus not being suitable to be related with active areas.
Prediction of the phenol removal capacity from water by adsorption on activated carbon
Authors: Galdino Ana Luísa , Oliveira José C. A. , Magalhaes Madson L. , Lucena Sebastião M. P.
Published: May 2021

Despite the improvement in understanding the structure of the activated carbons, the procedure for developing new carbonaceous materials suitable for the removal of phenolic compounds is still largely based on trial and error. Until now, there have been no predictive models to assist in the selection or synthesis of these adsorbents. Here, we apply molecular simulation to better understand the pore size–adsorption relationship in activated carbons. We simulated a set of phenol isotherms for different carbon pore sizes (8.9, 18.5, and 27.9 Å), named representative pores. The pore size of 8.9 Å is the most efficient in removing diluted phenol in water and was most effective at concentrations of 1.6 × 10−5 mol/L. The other pores are effective at concentrations of three orders of magnitude above this. A predictive approach for phenol removal capacity, based in the representative pore methodology, was proposed and validated for commercial activated carbon. Moreover, we present evidence that this method can be extended to other phenolic compounds.
Calibration of an in-situ fluorescence-based sensor platform for reliable BOD5 measurement in wastewater
Authors: Khamis K. , Bradley C. , Gunter H. J. , Basevi G. , Stevens R. , Hannah D. M.
Published: May 2021

Reliance on biochemical oxygen demand (BOD5) as an indicator of wastewater quality has hindered the development of efficient process control due to the associated uncertainty and lag-times. Surrogate measurements have been proposed, with fluorescence spectroscopy a promising technique. Yet, assessment of in-situ fluorescence sensors across multiple wastewater treatment plants (WwTPs), and at different treatment stages, is limited. In this study a multi-parameter sonde (two fluorescence peaks, turbidity, temperature and electrical conductivity) was used to provide a BOD5 surrogate measurement. The sonde was deployed at three WwTPs, on post primary settlement tanks (PST) and final effluent (FE). Triplicate laboratory measurements of BOD5, from independent laboratories were used to calibrate the sensor, with high variability apparent for FE samples. Site and process specific sensor calibrations yielded the best results (R2cv = 0.76–0.86; 10-fold cross-validation) and mean BOD5 of the three laboratory measurements improved FE calibration. When combining PST sites a reasonable calibration was still achieved (R2cv = 0.67) suggesting transfer of sensors between WwTPs may be possible. This study highlights the potential to use online optical sensors as robust BOD5 surrogates in WwTPs. However, careful calibration (i.e. replicated BOD5 measurements) is required for FE as laboratory measurements can be associated with high uncertainty.
Fizjologiczne procesy starzenia się kobiety i mężczyzny a płodność
Authors: Bassa Bożena
Published: May 2021

Starzenie się jest naturalnym procesem fizjologicznym, postępującym i nieodwracalnym. Wskutek starzenia zmniejsza się zdolność adaptacyjna organizmu oraz osłabieniu ulegają jego mechanizmy obronne. Procesom starzenia ulegają wszystkie gruczoły hormonalne, jednak najbardziej wyraźne zmiany zachodzą w jajnikach. Wraz z wiekiem stopniowo wygasa ich czynność, aż do menopauzy. Wygasaniu aktywności jajników, na skutek niedoborów hormonów jajnikowych towarzyszy zespół objawów klimakterycznych. U mężczyzn wraz z wiekiem stopniowo obniża się produkcja testosteronu oraz zmniejsza się liczba plemników – jednak płodność mężczyzny może być zachowana nawet do starości. Procesom starzenia się układu rozrodczego towarzyszy szereg dolegliwości związanych z niedoborem hormonów płciowych – m.in. osteoporoza.
Natural Thiazoline-Based Cyclodepsipeptides from Marine Cyanobacteria: Chemistry, Bioefficiency and Clinical Aspects
Authors: Dahiya Rajiv , Dahiya Sunita , Fuloria Neeraj Kumar , Jankie Satish , Agarwal Alka , Davis Vernon , Sahadeo Vijaya , Radhay Vishal , Ramsubhag Yashoda , Mullings Wellecia , Langford Zachary , Bedassie Zekiel , Fuloria Shivkanya
Published: May 2021

Background:

Peptides and peptide-based therapeutics are biomolecules that
demarcate a significant chemical space to bridge small molecules with biological therapeutics,
such as antibodies, recombinant proteins, and protein domains.

Introduction:

Cyclooligopeptides and depsipeptides, particularly cyanobacteria-derived
thiazoline-based polypeptides (CTBCs), exhibit a wide array of pharmacological activities
due to their unique structural features and interesting bioactions, which furnish them
as promising leads for drug discovery.

Methods:

In the present study, we comprehensively review the natural sources, distinguishing
chemistries, and pertinent bioprofiles of CTBCs. We analyze their structural peculiarities
counting the mode of actions for biological portrayals which render CTBCs as
indispensable sources for emergence of prospective peptide-based therapeutics. In this
milieu, metal organic frameworks and their biomedical applications are also briefly discussed.
To boot, the challenges, approaches, and clinical status of peptide-based therapeutics
are conferred.

Results:

Based on these analyses, CTBCs can be appraised as ideal drug targets that have
always remained a challenge for traditional small molecules, like those involved in protein-
protein interactions or to be developed as potential cancer-targeting nanomaterials.
Cyclization-induced reduced conformational freedom of these cyclooligopeptides contribute
to improved metabolic stability and binding affinity to their molecular targets.
Clinical success of several cyclic peptides provokes the large library-screening and synthesis
of natural product-like cyclic peptides to address the unmet medical needs.

Conclusion:

CTBCs can be considered as the most promising lead compounds for drug
discovery. Adopting the amalgamation of advanced biological and biopharmaceutical
strategies might endure these cyclopeptides to be prospective biomolecules for futuristic
therapeutic applications in the coming times.
Enzyme Replacement Therapy for Genetic Disorders Associated with Enzyme Deficiency
Authors: Marchetti Marialaura , Faggiano Serena , Mozzarelli Andrea
Published: May 2021

:

Mutations in human genes might lead to the loss of functional proteins, causing diseases. Among these genetic disorders, a large class is associated with the deficiency in metabolic enzymes, resulting in both an increase in the concentration of substrates and a loss in the metabolites produced by the catalyzed reactions. The identification of therapeu-tic actions based on small molecules represents a challenge to medicinal chemists because the target is missing. Alternative approaches are biology-based, ranging from gene and stem cell therapy, CRISPR/Cas9 technology, distinct types of RNAs, and enzyme replace-ment therapy (ERT). This review will focus on the latter approach that since the 1990s has been successfully applied to cure many rare diseases, most of them being lysosomal stor-age diseases or metabolic diseases. So far, a dozen enzymes have been approved by FDA/EMA for lysosome storage disorders and only a few for metabolic diseases. Enzymes for replacement therapy are mainly produced in mammalian cells and some in plant cells and yeasts and are further processed to obtain active, highly bioavailable, less degradable products. Issues still under investigation for the increase in ERT efficacy are the optimiza-tion of the interaction of the enzymes with cell membrane and internalization, the reduction in immunogenicity, and the overcoming of blood-brain barrier limitations when neuronal cells need to be targeted. Overall, ERT has demonstrated its efficacy and safety in the treatment of many genetic rare diseases, both saving newborn lives and improving pa-tients’ life quality, and represents a very successful example of targeted biologics.
Condensed Pyridopyrimidines and Pyridopyrazines Containing a Bridgehead Nitrogen Atom: Synthesis, Chemical Properties and Biological Activity
Authors: Slivka Mikhail V. , Korol Natalia I.
Published: May 2021

The investigation of effective and green synthetic routes to approach to novel fused
heterocycles with pyridopyrimidine and pyridopyrazine scaffolds stirs up broad interest from
scientists as they are capable of providing valuable properties such as anticancer and antimicrobial
activities and they are proved γ-secretase modulators, polymers, and corrosion inhibitors.
This causes a steady increase in the number of publications on titled condensed systems.
The present review article summarizes recent literature data from 2010 to 2020 on the
methods of synthesis, chemical transformations and biological properties of condensed
bicyclic systems of pyridopyrimidine and pyridopyrazine with a bridgehead nitrogen atom to
establish the current state of the art in this area.
Small-Molecule Inhibitors Targeting eIF4A in Leukemia
Authors: Jia Xiaofeng , Zhou Hong
Published: May 2021

Eukaryotic translation initiation factor 4A (eIF4A) is a highly conserved DEAD-box RNA
helicase in eukaryotes with ATPase and RNA helicase activities. eIF4A plays an important role in capdependent
translation at the initiation of mRNA translation, and carcinoma signal transduction pathways
are focused on cap-dependent translation. eIF4A is highly expressed in a variety of cancers, and
its high expression is associated with the degree of leukemia progression. Therefore, eIF4A, as a target
for tumor therapy, has become a hot research topic. Many small-molecule inhibitors targeting eIF4A
have been demonstrated in preclinical cancer model trials. The purpose of this review is to describe the
function of eIF4A and the development of eIF4A targeting inhibitors.