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Background There is a lack of knowledge on how patients with asthma or chronic obstructive pulmonary disease (COPD) are globally treated in the real world, especially with regard to the initial pharmacological treatment of newly diagnosed patients and the different treatment trajectories. This knowledge is important to monitor and improve clinical practice.Methods This retrospective cohort study aims to characterise treatments using data from four claims (drug dispensing) and four electronic health record (EHR; drug prescriptions) databases across six countries and three continents, encompassing 1.3 million patients with asthma or COPD. We analysed treatment trajectories at drug class level from first diagnosis and visualised these in sunburst plots.Results In four countries (USA, UK, Spain and the Netherlands), most adults with asthma initiate treatment with short-acting ß2 agonists monotherapy (20.8%–47.4% of first-line treatments). For COPD, the most frequent first-line treatment varies by country. The largest percentages of untreated patients (for asthma and COPD) were found in claims databases (14.5%–33.2% for asthma and 27.0%–52.2% for COPD) from the USA as compared with EHR databases (6.9%–15.2% for asthma and 4.4%–17.5% for COPD) from European countries. The treatment trajectories showed step-up as well as step-down in treatments.Conclusion Real-world data from claims and EHRs indicate that first-line treatments of asthma and COPD vary widely across countries. We found evidence of a stepwise approach in the pharmacological treatment of asthma and COPD, suggesting that treatments may be tailored to patients’ needs.

Abstract The intake plugging of an electrical submersible pump (ESP) has presented a formidable challenge to conventional ESP wells. Attention to cumulative solid deposition is essential since it intensifies the intake plugging severity and impedes ESP performance. We present a new approach to evaluate the ESP performance degradation during increased intake plugging severity. In particular, we employ the intake plugging factor, rate-derating factor, and affinity law to calculate the new ESP speed at different plugging conditions. We used Schlumberger PIPESIM software to perform nodal analysis of the newly calculated ESP speed. The result was validated using the actual field data and compared to the field cases that reported the intake plugging issue. The nodal analysis showed a steady maximum ESP head with zero rate derating at the shut-in point. The intake plugging factor caused a significant reduction in the ESP operating rate and increased pump intake pressure and annulus liquid level. Based on the existing intake plugging field data, we established the quantitative standard for the normal and abnormal intake plugging factor range. The observed results agreed with the field downhole data recorded during the intake plugging problem. We identified that regulating the ESP speed to the reduced operating rate could minimize unexpected pump stoppage. It is also possible to carefully monitor the intake plugging problem by combining the annulus liquid level, the signature of pump intake pressure, and a deadhead test.

Abstract The Hippo pathway’s main effector, Yes-associated protein (YAP), plays a crucial role in tumorigenesis as a transcriptional coactivator. YAP’s phosphorylation by core upstream components of the Hippo pathway, such as mammalian Ste20 kinase 1/2 (MST1/2), mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), and their substrate, large tumor suppressor 1/2 (LATS1/2), influences YAP’s subcellular localization, stability, and transcriptional activity. However, recent research suggests the existence of alternative pathways that phosphorylate YAP, independent of these core upstream Hippo pathway components, raising questions about additional means to inactivate YAP. In this study, we present evidence demonstrating that TSSK1B, a calcium/calmodulin-dependent protein kinase (CAMK) superfamily member, is a negative regulator of YAP, suppressing cellular proliferation and oncogenic transformation. Mechanistically, TSSK1B inhibits YAP through two distinct pathways. Firstly, the LKB1–TSSK1B axis directly phosphorylates YAP at Ser94, inhibiting the YAP–TEAD complex’s formation and suppressing its target genes’ expression. Secondly, the TSSK1B–LATS1/2 axis inhibits YAP via phosphorylation at Ser127. Our findings reveal the involvement of TSSK1B-mediated molecular mechanisms in the Hippo–YAP pathway, emphasizing the importance of multilevel regulation in critical cellular decision-making processes.

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P

Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model. Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (

Background: Chronic rhinosinusitis (CRS) is a common comorbid condition of asthma that affects the long-term outcome of asthmatic patients. CRS is a heterogeneous disease requiring multiple biomarkers to explain its pathogenesis. This study aimed to develop potential biomarkers for predicting CRS in adult asthmatic patients in a real-world clinical setting. Methods: This study enrolled 108 adult asthmatic patients who had maintained anti-asthmatic medications, including medium-to-high doses of inhaled corticosteroid plus long-acting β2-agonists, and compared clinical characteristics between patients with CRS (CRS group) and those without CRS (non-CRS group). CRS was diagnosed based on the results of paranasal sinus X-ray and/or osteomeatal-unit CT as well as clinical symptoms. Type-2 parameters, including blood eosinophil count, serum levels of periostin/dipeptidyl peptidase 10 (DPP10) and clinical parameters, such as FEV1% and fractional exhaled nitric oxide (FeNO), were analyzed. All biomarkers were evaluated by logistic regression and classification/regression tree (CRT) analyses. Results: The CRS group had higher blood eosinophil counts/FeNO levels and prevalence of aspirin-exacerbated respiratory disease (AERD) than the non-CRS group (n = 57, 52.8% vs. n = 75, 47.2%; P

Abstract Background Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse. Case presentation Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient’s symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment. Conclusion These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.

Recent advances in asthma research have led to the development of novel biologicals that hinder the pathological actions of key molecules in severe asthma. Traditional randomised controlled studies (RCTs), the gold standard for evaluating the efficacy and safety of medical interventions with excellent internal validity, have proven the clinical benefits and favourable safety profiles of type 2 biologicals in severe asthma. However, RCTs are not always ideal because of shortcomings such as limited external validity and practical issues in the management of severe asthma that cannot be solved through strictly designed clinical trials. Thus, the applicability of their findings may be questioned because treatment adherence is frequently poor in the real world. Real-world evidence includes a wide range of real-world data (RWD) collected from multiple sources in clinical practice, such as electronic medical records, healthcare insurance claims and retrospective or prospective patient registries. RWD may help clinicians decide how to manage patients with severe asthma. Real-world evidence is also gaining attention in addressing clinical questions not answered by traditional RCTs. Because there are various types of RWD with different possibilities and limitations, it is important to decide which type of RWD could be “fit for purpose” to address a specific question. This narrative review discusses the challenges and opportunities of RWD for evaluating the effectiveness and clinical outcomes of biological treatments for severe asthma.

A microfluidic chip is a micro-reactor that precisely manipulates and controls fluids. Zein is a group of prolamines extracted from corn that can form self-assembled nanoparticles in water or a low concentration of ethanol in a microfluidic chip. However, the zein nanoparticles have stability issues, especially in a neutral pH environment due to the proximity of the isoelectric point. This study was designed 1) to evaluate the effect of octenyl succinic anhydride (OSA) modified starch on the stability of zein nanoparticles formed using a microfluidic chip and 2) to apply the zein-OSA starch for encapsulation of nisin and evaluate its anti-microbial activity in a model food matrix. A T-junction configuration of the microfluidic chip was used to fabricate the zein nanoparticles using 1% or 2% zein solution and 0–10% (w/w) of OSA starch solution. The stability of the nanoparticles in various ionic strength environments was assessed. Encapsulation efficiency and anti-microbial activity of nisin in the zein nanoparticles against Listeria monocytogenes in a fresh cheese were measured. As the concentration of OSA starch increased from 0 to 10%, effective diameter increased from 117.8 ± 14.5 to 198.7 ± 13.9 nm without affecting polydispersity indexes and zeta-potential changed toward that of the modified starch indicating the zein surface coverage by the OSA starch. The zein-OSA starch nanoparticle complexes were more stable at various sodium chloride concentrations than the zein nanoparticles without OSA starch. The encapsulation efficiency of nisin was positively correlated with the OSA starch concentration. The anti-microbial activity of nisin in the fresh cheese also increased until 3-days of storage as the concentration of the OSA starch increased, which presented both a potential and challenge toward applications.

Abstract Background Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years. Methods This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed. Results A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397–3.550, P

Emerging portable near infrared (NIR) spectroscopic approaches coupled with data analysis and chemometric techniques provide opportunities for the rapid characterization of spray-dried products and process optimization. This study aimed to enhance the understanding of applying NIR spectroscopy in spray-dried samples by comparing two sample preparation strategies and two spectrometers. Two sets of whey protein–maltodextrin matrixes, one with a protein content gradient and one with a consistent protein content, were spray-dried, and the effect of the two preparation strategies on NIR calibration model development was studied. Secondly, a portable NIR spectrometer (PEAK) was compared with a benchtop NIR spectrometer (CARY) for the moisture analysis of prepared samples. When validating models with the samples with focused protein contents, the best PLS protein models established from the two sample sets had similar performances. When comparing two spectrometers, although CARY outperformed PEAK, PEAK still demonstrated reliable performance for moisture analysis, indicating that it is capable as an inline sensor.

Abstract Background Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals (

Background: IgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU. Methods: Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgETRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (

BackgroundMast cells are a key effector cell in the pathogenesis of chronic spontaneous urticaria (CSU) and activated by circulating FcεRI-specific IgG as well as IgE. This study evaluated the prevalence of circulating autoantibodies to FcεRIα in the sera of CSU patients.MethodsEighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled. To detect circulating autoantibodies (IgG/IgA/IgM) to FcεRIα, ELISA was done using YH35324 (as a solid phase antigen), and its binding specificity was confirmed by the ELISA inhibition test. The antibody levels were presented by the ratio of YH35324-preincubated to mock-preincubated absorbance values. Clinical and autoimmune parameters, including atopy, urticaria activity score (UAS), serum total/free IgE levels, serum antinuclear antibody (ANA) and autologous serum skin test (ASST) results, were assessed. The autoimmune group was defined if CSU patients had positive results to ASST and/or ANA.ResultsThe ratio of serum IgG to FcεRIα was significantly lower in CSU patients than in HCs (PConclusionsThis study confirmed the presence of IgG to FcεRIα in the sera of CSU patients, especially those with the autoimmune phenotype.

Successful sugar reduction in food products mimics the sensory and functional properties of the full sugar counterpart. The initial step of sugar reduction is to determine how the absence of sugar affects these properties. Descriptive analysis was conducted on four gel types (gelatin, ι-carrageenan, κ-carrageenan, and konjac glucomannan) and a range of sugar concentrations from 0–20% w/v to create a sensory profile of model confectionary gels for comparison to instrumental texture profile analysis data. The sensory descriptive data were analyzed using analysis of variance and principal component analysis. Correlation analysis, cluster analysis, and partial least squares regression (PLS-R) were used to compare and correlate sensory and instrumental data. Regardless of sugar concentration, sensory analysis primarily clustered samples by gelling agent type, such as in the case of konjac glucomannan consistently being characterized as chewy. Cohesion and gumminess were correlated highly with melt-in-mouth and a jiggly texture, while adhesion and fracturability were negatively correlated. In the PLS-R samples biplot, gelatin and iota carrageenan samples were located near these attributes indicating their aptness as descriptors. In conclusion, descriptive analysis provided a more discriminating method for characterizing model confectionary gels.

Crossfield is located in the province of Alberta in Canada and is one of the most well-known reservoirs of hydrocarbons. Since the 1950s, there has been continuous exploitation of more than 10 formations such as Cardium, Viking, Ellerslie, Elkton, Shunda, and Wabamun. Because of its location near the Foothills, the southwestern part of the Western Canada Sedimentary Basin, the Crossfield area has a complex geology and relatively deeper reservoirs, therefore requiring an in-depth examination of each formation. In this study, geological, technical, and economic analyses were performed on each formation within the 10 sections of the study lands in the Crossfield area. As the result of the study, there was potential for drilling 48 horizontal wells in the Cardium A zone and the Viking formation. In addition, it turned out to be economically feasible even at the WTI price of 60 dollars per barrel considering Alberta’s Royalty Framework, which is determined by the production rate and the price of oil, and the Horizontal Oil New Well Royalty Rate feature. A further study is required to investigate the exploitation potential of the Cardium B zone, the Ellerslie, and the Elkton formations in this area.

Cefaclor, a second-generation oral cephalosporin, is the most frequently prescribed cephalosporin in Korea. Studies, however, have yet to analyze the incidence of cefaclor-associated adverse drug reactions (ADRs), including hypersensitivity (HS), according to total national usage rates. This study aimed to investigate the incidence rates and clinical features of cefaclor ADRs reported to the Korean Adverse Event Reporting System (KAERS) and Health Insurance Review and Assessment Service (HIRA) database for the most recent 5 years. Reviewing the HIRA database, which contains information on all insurance claims, including prescribed medications and patient demographics, we identified the total number of individuals who had been prescribed cefaclor and other cephalosporins including 2nd generation without cefaclor and 3rd generation antibiotics from January 2014 to December 2018. Additionally, we retrospectively analyzed all ADRs reported to the KAERS for these drugs over the same study period. Incidence rates for ADRs, HS, and anaphylaxis to cefaclor were 1.92/10,000 persons, 1.17/10,000 persons, and 0.38/10,000 persons, respectively, lower than those to other 2nd and 3rd cephalosporins. Among all ADRs, HS (60.9% vs. 43.6% vs. 44.8%, P

The rise of machine learning (ML) has created an explosion in the potential strategies for using data to make scientific predictions. For physical scientists wishing to apply ML strategies to a particular domain, it can be difficult to assess in advance what strategy to adopt within a vast space of possibilities. Here we outline the results of an online community-powered effort to swarm search the space of ML strategies and develop algorithms for predicting atomic-pairwise nuclear magnetic resonance (NMR) properties in molecules. Using an open-source dataset, we worked with Kaggle to design and host a 3-month competition which received 47,800 ML model predictions from 2,700 teams in 84 countries. Within 3 weeks, the Kaggle community produced models with comparable accuracy to our best previously published 'in-house' efforts. A meta-ensemble model constructed as a linear combination of the top predictions has a prediction accuracy which exceeds that of any individual model, 7-19x better than our previous state-of-the-art. The results highlight the potential of transformer architectures for predicting quantum mechanical (QM) molecular properties.

Electrical submersible pump (ESP) operation is compromised by free gas, resulting in premature pump failure and production losses in new wells. It is essential to detect the onset of abnormal operations. We develop a model that predicts abnormal ESP operation when the free gas level increases in the pump. The model compares operation parameters with the parameters of normal operating ranges; it shuts down the ESP when necessary. We used a Schlumberger PIPESIM software (version 2017.01) to perform nodal analysis technique; we tested the model using the other multiphase correlation model and field case studies (where the gas problem in ESP was reported). We employ a homogenous model to calculate the differential pump pressures at various gas volume fractions. Nodal analysis of the intake and discharge point predicted the commencement of abnormal ESP conditions and the associated parameters (critical gas fraction, minimum operating pump intake pressure, and pump discharge pressure). The model results were similar to other surging correlation models (e.g., Romero, Dunbar, Turpin, Cirilo, and Zhou models); they were also identical to field case studies. We identify three performance stability phases when an ESP is exposed to free gas. These are the normal and abnormal operating ranges, as well as the ESP shutdown condition. Modeling permits careful monitoring of ESP operations that can be compromised by free gas.

The chromatin remodeler RSF1 is enriched at mitotic centromeres but its function there is poorly understood. Here, the authors show that RSF1 regulates H2A phosphorylation and acetylation at mitotic centromeres and contributes to chromosome stability.

For the stable supply of oil and gas resources, industry is pushing for various attempts and technology development to produce not only existing land fields but also deep-sea, where production is difficult. The development of flow assurance technology is necessary because hydrate is aggregated in the pipeline and prevent stable production. This study established a system that enables hydrate diagnosis in the gas pipeline from a flow assurance perspective. Learning data were generated using an OLGA simulator, and temperature, pressure, and hydrate volume at each time step were generated. Stacked auto-encoder (SAE) was used as the AI model after analyzing training loss. Hyper-parameter matching and structure optimization were carried out using the greedy layer-wise technique. Through time-series forecast, we determined that AI diagnostic model enables depiction of the growth of hydrate volume. In addition, the average R-square for the maximum hydrate volume was 97%, and that for the formation location was calculated as 99%. This study confirmed that machine learning could be applied to the flow assurance area of gas pipelines and it can predict hydrate formation in real time.

To improve the dimensional thermal stability of polyethylene terephthalate (PET), a poly(ethylene glycol 1,4-cyclohexane dimethylene (CHDM) isosorbide (ISB) terephthalate) (PEICT) known as ECOZEN®T110 (EZT) was introduced into PET using a melt blending technique. The miscibility, morphology, and thermal properties of the PET/EZT samples were investigated. The introduction of amorphous EZT into semi-crystalline PET increased the glass transition temperature (Tg) but decreased the crystallinity, which could be related to the transesterification reaction. By adding EZT contents up to 20%, the PET/EZT samples showed a single Tg, which indicated the miscibility between PET and EZT. However, two Tg values were observed in the PET/EZT samples with higher EZT contents (30–70%), indicating partial miscibility. This may have been due to the slightly different rheological and thermodynamic parameters that were affected by a higher ratio of bulky (rigid ISB and ductile CHDM) groups in EZT. However, the heat distortion temperature of the PET/EZT samples remarkably increased, which indicated that the dimensional stability was truly enhanced. Although the crystallinity of the PET/EZT samples decreased with increasing EZT content, the tensile strength and Young’s modulus decreased slightly. Based on these results, the as-prepared PET/EZT samples with high dimensional stability can be used as a high-temperature polymeric material in various applications.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates reactive oxygen/nitrogen species (ROS/RNS)-dependent apoptosis in cancer cells. We investigate the capability of PAM and TRAIL (PAM/TRAIL) combination therapy to overcome TRAIL resistance and improve the anticancer efficacy of TRAIL. The combinatorial treatment of PAM and TRAIL shows synergistic effects on growth inhibition in TRAIL-resistant cancer cells via augmented apoptosis by two attributes. DR5 (TRAIL-R2) transcription by CHOP is upregulated in a PAM-generated ROS/RNS-dependent manner, and PAM itself upregulates PTEN expression mediated by suppression of miR-425 which is involved in Akt inactivation, leading to increased apoptosis induction. Treatment of cancer cell lines with the antioxidant N-acetylcysteine reduces the extent of membrane dysfunction and the expression of both CHOP-DR5 and miR-425-PTEN axes, attenuating PAM/TRAIL-induced cancer cell apoptosis. These data suggest that PAM/TRAIL treatment is a novel approach to sensitizing cancer cells to TRAIL-induced apoptosis and overcoming TRAIL resistance. PAM is a promising candidate for further investigations as a chemotherapeutic sensitizer in the treatment of cancer.

Coalbed methane (CBM) content is generally estimated using the isotherm theory between pressure and adsorbed amounts of methane. It usually determines the maximum content of adsorbed methane or storage capacity. However, CBM content obtained via laboratory experiment is not consistent with that in the in-situ state because samples are usually ground, which changes the specific surface area. In this study, the effect of the specific surface area relative to CBM content was investigated, and diffusion coefficients were estimated using equilibrium time analysis. The differences in adsorbed content with sample particle size allowed the determination of a specific surface area where gases can adsorb. Also, there was an equilibrium time difference between fine and lump coal, because more time is needed for the gas to diffuse through the coal matrix and adsorb onto the surface in lump coal. Based on this, we constructed a laboratory-scale simulation model, which matched with experimental results. Consequently, the diffusion coefficient, which is usually calculated through canister testing, can be easily obtained. These results stress that lump coal experiments and associated simulations are necessary for more reliable CBM production analysis.

Most shale gas reservoirs have extremely low permeability. Predicting their fluid transport characteristics is extremely difficult due to complex flow mechanisms between hydraulic fractures and the adjacent rock matrix. Recently, studies adopting the dynamic modeling approach have been proposed to investigate the shape of the flow regime between induced and natural fractures. In this study, a production history matching was performed on a shale gas reservoir in Canada’s Horn River basin. Hypocenters and densities of the microseismic signals were used to identify the hydraulic fracture distributions and the stimulated reservoir volume. In addition, the fracture width decreased because of fluid pressure reduction during production, which was integrated with the dynamic permeability change of the hydraulic fractures. We also incorporated the geometric change of hydraulic fractures to the 3D reservoir simulation model and established a new shale gas modeling procedure. Results demonstrate that the accuracy of the predictions for shale gas flow improved. We believe that this technique will enrich the community’s understanding of fluid flows in shale gas reservoirs.

In this study, the effect of a composition (protein to fat (P/F) ratio) and a processing condition (homogenization pressure for emulsification of cheese milk) on the texture, microstructure, and bioaccessibility of vitamin D3 of a model acid coagulated fresh cheese was evaluated. It was hypothesized that increasing P/F ratios (0.9, 1.3, 1.7, and 2) and homogenization pressures (17, 50, 75, and 150 MPa) will decrease the particle size of the cheese milk emulsion. The decreased emulsion particle size will result in a more rigid and elastic cheese matrix with smaller pore sizes, with an increased interfacial surface area of fat particles, which will then improve the bioaccessibility of vitamin D3. The P/F ratio exhibited a positive impact on the texture in a large deformation analysis. On the other hand, the effect of the P/F ratio and homogenization pressure was not significant on rheological properties of the cheese using a small deformation by means of a frequency sweep test, nor the porosity determined by environmental scanning electron microscopy (ESEM). These results suggested that the modification of the microstructure of acid coagulated fresh cheeses required other variables than P/F ratio and homogenization pressure probably due to a compression step after curd formation. Interestingly, the bioaccessibility of vitamin D3 measured by in vitro digestion was reduced as P/F ratio and homogenization pressure increased, which may indicate a reinforced protein–protein interaction that affected protein hydrolysis.

Dicer, a ribonuclease III enzyme, is required for the maturation of microRNAs. To assess its role in cerebellar and medulloblastoma development, we genetically deleted Dicer in Nestin-positive neural progenitors and in mice lacking one copy for the Sonic Hedgehog receptor, Patched 1. We found that conditional loss of Dicer in mouse neural progenitors induced massive Trp53-independent apoptosis in all proliferative zones of the brain and decreased proliferation of cerebellar granule progenitors at embryonic day 15.5 leading to abnormal cerebellar development and perinatal lethality. Loss of one copy of Dicer significantly accelerated the formation of mouse medulloblastoma of the Sonic Hedgehog subgroup in Patched1-heterozygous mice. We conclude that Dicer is required for proper cerebellar development, and to restrain medulloblastoma formation.

This article addresses the state of the art of bioleaching research published in South Korean Journals. Our research team reviewed the available articles registered in the Korean Citation Index (KCI, Korean Journal Database) addressing the relevant aspects of bioleaching. We systematically categorized the target metal sources as follows: mine tailings, electronic waste, mineral ores and metal concentrates, spent catalysts, contaminated soil, and other materials. Molecular studies were also addressed in this review. The classification provided in the present manuscript details information about microbial species, parameters of operation (e.g., temperature, particle size, pH, and process length), and target metals to compare recoveries among the bioleaching processes. The findings show an increasing interest in the technology from research institutes and mineral processing-related companies over the last decade. The current research trends demonstrate that investigations are mainly focused on determining the optimum parameters of operations for different techniques and minor applications at the industrial scale, which opens the opportunity for greater technological developments. An overview of bioleaching of each metal substrate and opportunities for future research development are also included.