bluuebunny/crossref_metadata_2025 huggingface dataset:
The structure balance of gene-gene networks beyond pairwise interactions
Authors: Allahyari Nastaran , Kargaran Amir , Hosseiny Ali , Jafari G. R.
Published: October 2021

Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared with the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles the nonessential gene network is more balanced compared to the essential network.
Structural basis of ATP-dependent high-fidelity epigenome maintenance
Authors: Wang Juncheng , Catania Sandra , Wang Chongyuan , de la Cruz M. Jason , Rao Beiduo , Madhani Hiten D. , Patel Dinshaw J.
Published: October 2021

Epigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance-type cytosine methyltransferase identified in the fungal or protist kingdoms. DNMT5 requires ATP and displays exquisite hemimethyl-DNA specificity. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out the DNA duplex. ATP binding then triggers a striking structural reconfiguration of the methyltransferase catalytic pocket that enables cofactor binding, completion of base-flipping, and catalysis. Unmethylated DNA binding fails to open cofactor pocket and subsequent ATP binding triggers its ejection to ensure fidelity. This chaperone-like, enzyme-remodeling role of the SNF2 domain illuminates how energy can be used to enable faithful epigenetic memory.

Highlights

Structures of DNMT5 reveal mechanism of ATP-dependent DNA methylation

Hemimethylated CpG recognition triggers partial base flipping of the target cytosine

Hemimethylated DNA induces rigid body rotation to activate the SNF2 ATPase domain

MTase catalytic pocket is remodeled by the SNF2 ATPase to achieve specificity
Targeting MLL methyltransferases enhance the anti-tumor effects of PI3K inhibition in hormone receptor-positive breast cancer
Authors: Jones RB. , Farhi J. , Adams M. , Parwani K. , Zecevic M. , Cooper G. , Lee RS. , Hong AL. , Spangle JM
Published: October 2021

The high frequency of aberrant PI3K pathway activation in hormone receptor-positive (HR+) breast cancer has led to the development, clinical testing, and approval of the p110α-selective PI3K inhibitor alpelisib. The limited clinical efficacy of alpelisib and other PI3K inhibitors is partially attributed to the functional antagonism between PI3K and estrogen receptor (ER) signaling, which is mitigated via combined PI3K inhibition and endocrine therapy. We and others have previously demonstrated a chromatin-associated mechanism by which PI3K supports cancer development and antagonizes ER signaling through the modulation of H3K4 methylation. Here we show that inhibition of the H3K4 histone methyltransferase MLL1 in combination with PI3K inhibition impairs HR+ breast cancer clonogenicity and cell proliferation. While combined PI3K/MLL1 inhibition reduces AKT effector signaling and H3K4 methylation, MLL1 inhibition increases PI3K effector signaling and upregulates the expression of receptor tyrosine kinase signaling cascades upstream of and including AKT. These data reveal a feedback loop between MLL1 and AKT in which MLL1 inhibition reactivates AKT. We additionally show that combined PI3K and MLL1 inhibition synergizes to cause cell death in in vitro and in vivo models of HR+ breast cancer, which is enhanced by the additional genetic ablation of the H3K4 methyltransferase and AKT target MLL4. Together, our data provide evidence of a feedback mechanism connecting histone methylation with AKT and may support the preclinical development and testing of pan-MLL inhibitors.

Significance Statement

Pharmacological inhibition of PI3K provides limited efficacy in PIK3CA-mutated, HR+ breast cancers. Here the authors leverage PI3K/AKT-driven chromatin modification to identify MLL histone methyltransferases as a therapeutic target. Dual PI3K and MLL inhibition synergize to reduce clonogenicity and cell proliferation while enhancing apoptosis in in vitro models, and induces tumor regression in xenograft models of PI3K-activated, HR+ breast cancer. Furthermore, MLL1 inhibition reveals a feedback loop leading to AKT hyperactivation, which is relieved with combined PI3K/MLL inhibition. These findings demonstrate the utility of MLL inhibitors for the treatment of some solid cancers, as patients with HR+ breast cancer characterized by PIK3CA mutation may derive clinical benefit from combined PI3K/MLL inhibition.
Deafening‐induced rapid changes to spine synaptic connectivity in the adult avian vocal basal ganglia
Authors: ZHOU Xiaojuan , CHEN Yalan , PENG Jikan , ZUO Mingxue , SUN Yingyu
Published: October 2021

The basal ganglia have been implicated in auditory‐dependent vocal learning and plasticity in human and songbirds, but the underlying neural phenotype remains to be clarified. Here, using confocal imaging and three‐dimensional electron microscopy, we investigated striatal structural plasticity in response to hearing loss in Area X, the avian vocal basal ganglia, in adult male zebra finch (Taeniopygia guttata). We observed a rapid elongation of dendritic spines, by approximately 13%, by day 3 after deafening, and a considerable increase in spine synapse density, by approximately 61%, by day 14 after deafening, compared with the controls with an intact cochlea. These findings reveal structural sensitivity of Area X to auditory deprivation and suggest that this striatal plasticity might contribute to deafening‐induced changes to learned vocal behavior.
Seed traits and rodent community interact to determine seed fate: evidence from both enclosure and field experiments
Authors: HOU Xiang , ZHANG Bo , STEELE Michael A. , HAN Ning , FENG Tuo , WANG Jing , CHEN Xiaoning , AN Xiaolei , CHANG Gang
Published: October 2021

Animal‐mediated seed dispersal is an important ecological process in which a strong mutualism between animals and plants can arise. However, few studies have examined how a community of potential seed dispersers interacts with sympatric seed trees. We employed a series of experiments in the Qinling Mountains in both semi‐natural enclosure and the field to assess the interactions among 3 sympatric rodent species and 3 Fagaceae tree seeds. Seed traits all showed similar tannin levels but markedly different physical traits and nutritional contents. We found that seeds with heavy weight, thick coat, and high nutritional contents were less likely to be eaten in situ but more often to be eaten after dispersal or hoarded by rodents. These results support both the handling time hypothesis and the high nutrition hypothesis. Surprisingly, we also found that rodents, maybe, preferred to consume seeds with low levels of crude fiber in situ, and to harvest and hoard those with high levels of crude fiber for later consumption. The sympatric rodent species, Cansumys canus, the largest rodent in our study, harvested and hoarded more Quercus variabilis seeds with high physical and nutritional traits, while Apodemus draco, the smallest rodent, harvested more Q. serrata seeds with low physical and nutritional traits, and Niviventer confucianus harvested and hoarded more Q. aliena seeds with medium physical and nutritional traits. Our study demonstrates that different seed traits play different roles in influencing the seed fate and the shaping of mutualism and predation interactions within a community of rodent species.
Are current cut‐off values of 11‐DOC in children useful for assessing suspected nonclassical congenital adrenal hyperplasia due to 11β‐hydroxylase deficiency?
Authors: Barash Galia , Drach Lior , Naugolni Larisa , Yacoel Tamar , Bistritzer Tzvi , Rachmiel Marianna
Published: October 2021

Objective

A nonclassic form of 11β‐hydroxylase deficiency (NC11β‐OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11‐deoxycortisol (11‐DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11‐DOC level cutoffs. One of the accepted references for 11‐DOC levels for the paediatric population was published in 1991 by Lashansky et al.

Aim

To determine the correlation between 11‐DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11β‐OHD.

Design

A retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients’ medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11‐DOC cut‐off levels according to Lashansky for sex and age, and according to commercial kit cut‐offs.

Results

Data were complete at presentation for 136 patients. Long‐term clinical data were documented for 98 patients, mean follow‐up duration of 3.1 years (1.37–5.09). There was no statistically significant difference in the number of cases with elevated 11‐DOC according to both cut‐offs and early puberty, premature adrenarche nor acne. Follow‐up data demonstrated no statistically significant difference in the number of cases with elevated 11‐DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism.

Conclusions

Basal and corticotropin stimulated 11‐DOC levels were not significantly elevated above the 1.5 times cut‐offs according to paediatric‐specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11β‐OHD.
Breaking down “harassment” to characterize trends in human interaction cases in Maine's pinnipeds
Authors: Newcomb Emma , Walk Dominique , Haverkamp Holland , Doughty Lynda , Todd Sean , Seton Rosemary , Jones Lindsey , Cammen Kristina
Published: October 2021

Recent marine mammal recovery and growth of human populations in coastal areas has led to increased human harassment of protected pinniped populations. Yet, current monitoring approaches lack the necessary resolution to describe this emerging issue. We therefore propose a new classification scheme for monitoring of marine mammal–human interaction (HI), which defines categories based on the type of human behavior and associated risks to the animal. Among harbor, harp, and gray seal strandings (N = 3,525) from 2007 to 2019 in Maine, United States, evidence of HI was reported in 14.72% of strandings, with the majority (75.34%) of these cases involving harassment. The number of HI reports increased over time, particularly in the southern region of the state, and an analysis of geographic hotspots further identifies emerging areas of concern. Variation in the rate and type of HI among species, age classes, and seasons reflect differences in pinniped life history. The most commonly observed types of harassment included human approach, physical contact, and displacement. By breaking down harassment, we aim to inform ongoing mitigation efforts and contribute to our understanding of the impact of HI on marine mammal health, as well as offer a transferable methodological approach to monitoring human–wildlife interaction.
Inferring the impact of past climate changes and hunting on the South American sea lion
Authors: Weinberger Constanza S. , Vianna Juliana A. , Faugeron Sylvain , Marquet Pablo A.
Published: October 2021

Aim

Many pinniped species have experienced drastic demographic changes due to their interaction with humans. Most studies, however, have failed to detect recent bottlenecks in otariids from genetic data. The South American Sea Lion Otaria flavescens have a long history of population changes associated with interglacial expansion and hunting to almost extinction. This study aimed at investigating these different demographic fluctuations integrating population genetics and phylogeographic approaches.

Location

Pacific coast of South America.

Methods

Eighty‐five samples from the Chilean coast were collected. Eight microsatellite loci were genotyped, and D‐Loop mitochondrial DNA (mtDNA) sequenced. Genetic diversity was assessed, and tests of recent genetic bottlenecks were performed. Past demographic changes were inferred based on neutrality tests, adjustment of a sudden expansion model and Bayesian skyline plots. The magnitude and timing of the different population size changes were further investigated through approximate Bayesian computation (ABC) of coalescent inferences.

Results

The mtDNA shows relatively high diversity (h = 0.98 and π = 0.01) compared to most otariids, corroborates the divergence between Pacific and Atlantic populations, around 80,000 years ago (ya), and revealed a secondary contact zone in the Magellan strait. Microsatellite data support a second genetic discontinuity at 40°S, associated with post‐glacial colonization of Patagonia. ABC analyses confirmed that glaciation affected the effective population size (Ne) all along the Pacific Coast, between ~50,000 and 15,000 ya. A strong reduction of Ne was also inferred for the hunting period (73–66 ya from sampling).

Main conclusions

O. flavescens shows clear signatures of susceptibility to climatic and anthropogenic disturbances and a spatial genetic structure that should be taken into account in the context of management and conservation policies. Yet, despite a recent history of demographic bottlenecks, the genetic diversity remains high, likely a consequence of the demographic dynamics in otariids, characterized by large and connected metapopulations.
The politics of last resort lending and the Overend & Gurney crisis of 1866
Authors: Schneider Sabine
Published: October 2021

News of the insolvency of Overend, Gurney, & Company on 10 May 1866 generated a scramble for funds in the City of London and urgent appeals to the Bank of England. The banking panic triggered by the collapse of the prominent British discount house became one of the Bank's most tumultuous modern crises. This article investigates the politics of the Bank's liquidity provision during the 1866 crisis, and in the ensuing months of financial stringency. By assessing the correspondence, speeches, and publications of Governors, City figures, and financial journalists, the article finds that the Bank's evolving approach to crisis lending was decisively shaped by its commercial objectives and a prolonged struggle to preserve its autonomy. When confronted with the 1866 crisis, the Bank adopted a pragmatic stance towards the market, which accommodated the credit needs of the City without sacrificing either its privileged legal status or its shareholders’ interests. Its Governors’ rhetorical pursuit of ‘constructive ambiguity’ during the post‐crisis months succeeded in both limiting moral hazard and consolidating the Bank's discretionary powers.
Enacting culturally sustaining immersion pedagogy through SFL and translanguaging design
Authors: Troyan Francis John , King Nicole , Bramli Ahmed
Published: October 2021

Framed within the discussions of the knowledge base for language immersion teachers, this article presents a qualitative case study of a first‐year Grade 2 French immersion teacher's enactment of his systemic functional linguistic (SFL) knowledge to position his students in a culturally sustaining genre pedagogy. We examined interactive events and interview data to understand how Ahmed deployed his SFL knowledge base to position four African American students in classroom interactions as they deconstructed and reconstructed focal genres in this second‐grade French immersion classroom. Our findings revealed that Ahmed positioned his students in three ways: as an inclusive classroom community, as readers and writers, and as language analysts. Likewise, the students took up roles as genre analysts, active language users, and engaged community members. The findings also demonstrated that Ahmed selectively deployed his linguistic resources in varieties of French and English to connect with his students, create community with them, and achieve his instructional goals within a translanguaging space (e.g., Tian, 2021; Wei, 2011). These findings point to the potential of SFL and translanguaging pedagogy as a flexible and dynamic knowledge base for enacting culturally sustaining immersion education.
Patients as team members: Factors affecting involvement in treatment decisions from the perspective of patients with a chronic condition
Authors: Buljac‐Samardzic Martina , Clark Mark A. , van Exel N. Job. A. , van Wijngaarden Jeroen D. H.
Published: October 2021

Background

Active patient involvement in treatment decisions is seen as a feature of patient‐centred care that will ultimately lead to better healthcare services and patient outcomes. Although many factors have been identified that influence patient involvement in treatment decisions, little is known about the different views that patients have on which factors are most important.

Objective

This study explores the views of patients with a chronic condition on factors influencing their involvement in treatment decisions.

Design

Q‐methodology was used to study the views of patients. Respondents were asked to rank a set of 42 statements from the least important to the most important for active patient involvement in treatment decision‐making. The set of 42 statements was developed based on a literature search and a pilot in which two external researchers, 15 patients and four healthcare professionals participated. A total of 136 patients with one of three major chronic conditions were included: diabetes types 1 and 2, respiratory disease (i.e., chronic obstructive pulmonary disease and asthma) and cancer (i.e., breast cancer and prostate cancer). Data were collected in a face‐to‐face interview setting in the Netherlands.

Results

Four distinct views on the factors influencing active patient involvement were identified among patients with a chronic condition. (1) Enabled involvement: the extent to which patients are facilitated and empowered to participate will lead to patient involvement. (2) Relationship‐driven involvement: the relationship between patients and healthcare professionals drives patient involvement. (3) Disease impact‐driven involvement: the severity of disease drives patient involvement. (4) Cognition‐driven involvement: knowledge and information drive patient involvement.

Discussion and Conclusion

From the patients' perspective, this study shows that there is no one‐size‐fits‐all approach to involving patients more actively in their healthcare journey. Strategies aiming to enhance active patient involvement among patients with a chronic condition should consider this diversity in perspectives among these patients.

Patient Contribution

Patients are the respondents as this study researches their perspective on factors influencing patient involvement. In addition, patients were involved in pilot‐testing the statement set.
Impaired Lactation: Review of Delayed Lactogenesis and Insufficient Lactation
Authors: Farah Erin , Barger Mary K. , Klima Carrie , Rossman Beverly , Hershberger Patricia
Published: October 2021

It is estimated that as many as 1 in 20 women worldwide are unable to successfully breastfeed or provide adequate nutrition for their infants through their breast milk alone. Compromised nutrition in the early stages of life places the infant at risk for insufficient growth as well as serious and potentially disabling or life‐threatening complications. This review summarizes risk factors associated with impaired lactation that may result in either delayed lactogenesis or insufficient lactation. The risk factors for insufficient lactation are categorized into preglandular, glandular, and postglandular causes. Impaired lactation can occur despite maternal motivation, knowledge, support, and appropriate breastfeeding technique. Although there is no clear way to predict who will experience impaired lactation, knowledge about the risk factors can enable health care professionals to better identify at‐risk mother‐infant dyads. Early intervention may help prevent infant complications associated with inadequate nutritional intake.
Personality differences in the occurrence and affective correlates of daily positive events
Authors: Klaiber Patrick , Wen Jin H. , Ong Anthony D. , Almeida David M. , Sin Nancy L.
Published: October 2021

Objective

Previous research shows that Neuroticism predicts exposure and affective reactivity to daily stressors. Zautra and colleagues extended this work to daily positive events. Building on these frameworks, we examined the Big Five personality traits as predictors of the occurrence and affective correlates of daily positive events.

Method

Participants in two national U.S. daily diary studies (NSDE 2: N = 1,919 and NSDE Refresher: N = 778; aged 25–84) reported daily positive events, emotions specific to the events, and daily affect for 8 consecutive days.

Results

In parallel analyses in both samples, Extraversion and in the NSDE Refresher sample only Openness (but not Neuroticism, Conscientiousness, or Agreeableness) predicted more frequent positive event occurrence. All Big Five traits were associated with one or more emotional experiences (e.g., calm, proud) during positive events. Neuroticism predicted greater event‐related positive affect in the NSDE 2 sample, whereas Agreeableness was related to more event‐related negative affect in the NSDE Refresher sample.

Conclusions

The Big Five personality traits each provided unique information for predicting positive events in daily life. The discussion centers on potential explanations and implications for advancing the understanding of individual differences that contribute to engagement in positive experiences.
Comparative study on the chemical composition of different bones/parts of bones in growing pigs differently supplied with inorganic phosphorus and phytase
Authors: Rieger Hanna , Ratert Christine , Wendt Michael , Schwennen Cornelia , Kamphues Josef
Published: October 2021

From the veterinarian point of view, the precise assessment of the phosphorus (P) supply of pigs is of great interest, especially in cases of clinical disorders like ‘leg weakness’ or lameness when bone mineralisation may be disturbed. Thus, the question arises which bone is most suitable for diagnostic purposes and is reflecting changes in dietary P supply most clearly. Thirty‐six growing pigs (BHZP db.Viktoria x Piétrain, about eleven weeks old, mean bw: 28.3 ± 3.44 kg) were allotted to three groups differently supplied with P by receiving a diet either supplemented with inorganic P (iP) and phytase (500 FTU/kg; controls/group C), without iP but phytase added (500 FTU/kg; group 1) or containing only endogenous phytase (group 2). The inclusion of iP resulted in total P contents in diets for group C of 4.76 and 4.23 g/kg as fed from 28 to 57 and >57 kg body weight (bw), respectively. In diets for group 1 and 2, the corresponding P contents were 3.08/2.72 g/kg as fed (group 1) and 3.08/2.88 g/kg as fed (group 2). On days 26, 47 and 82 of the dietary treatment, four pigs of each group were euthanised. Furthermore, four additional pigs were euthanised one day before starting the experiment. Standardised samples of the femur (distal part), tibia/fibula (proximal part) and os metatarsale III (MT III, in toto) were taken during dissection and submitted to chemical analysis. At all time points, pigs of group C had significantly higher ash contents in all types of bone samples compared to pigs from group 1 and 2. Relative differences between means of groups (C = 100%) were less for the ash content in MT III (reduction by up to −9.1%) compared to the distal femur and the proximal tibia/fibula (reduction by up to −23.2 resp. −22.7%). Variation coefficient (irrespective of group and time point) was lower for ash content in MT III (4.29%) compared to the distal femur and the proximal tibia/fibula (both: 11.8%). Under the conditions of this study, ash contents of the distal femur and the proximal tibia/fibula reflected the different P supply more pronounced indicating higher sensitivity compared to MT III.
p‐Coumaric acid attenuates high‐fat diet‐induced oxidative stress and nephropathy in diabetic rats
Authors: Mani Akhand , Kushwaha Kriti , Khurana Navneet , Gupta Jeena
Published: October 2021

The prevalence of persistent hyperglycaemia during diabetes, impair antioxidant defence system and generate reactive oxygen species, which majorly contribute to its progression and associated complications. Phytochemicals were suggested to scavenge‐free radicals and exert antioxidant effects required to improve insulin sensitivity and reduce the occurrence of diabetes‐associated complications. We hypothesise that a phenolic phytochemical p‐coumaric can reduce diabetes‐induced oxidative stress and improve diabetes‐associated nephropathy in rats. The aim of this study is to analyse the protective effects of p‐coumaric acid against diabetes‐induced oxidative stress and nephropathy in high‐fat diet‐induced diabetic rats. The oral feeding of p‐coumaric acid (20 mg/kg for 12 weeks) was found to significantly decrease the elevated levels of blood glucose in high‐fat diet‐induced type 2 diabetic rats. p‐Coumaric acid treatment also decreases the kidney weight whilst increasing the total body weight of diabetic rats. Furthermore whilst evaluation of the different renal functioning tests, p‐coumaric acid significantly improves histopathological changes and the levels of urea, creatinine and uric acid in serum of diabetic rats, which was otherwise elevated under diabetic conditions. Our results also highlight that p‐coumaric acid is an efficient compound with antioxidant properties and improves the diabetes‐induced change in lipid peroxidation and activities of antioxidant enzymes: catalase, glutathione‐S‐transferase and superoxide dismutase. p‐Coumaric acid thus possesses the potential to prevent diabetic nephropathy by reducing oxidative stress and can thus serve as a potential drug target for pharmaceutical companies.
Scheduling of Physicians with Time‐Varying Productivity Levels in Emergency Departments
Authors: Zaerpour Farzad , Bijvank Marco , Ouyang Huiyin , Sun Zhankun
Published: October 2021

Emergency department (ED) overcrowding and long patient wait times have become a worldwide problem. We propose a novel approach to assigning physicians to shifts such that ED wait times are reduced without adding new physicians. In particular, we extend the physician rostering problem (PRP) by including heterogeneity among emergency physicians in terms of their productivity (measured by the number of new patients seen in 1 hour) and by considering the stochastic nature of patient arrivals and physician productivity. We formulate the PRP as a two‐stage stochastic program and solve it with a sample average approximation and the L‐shaped method. To formulate the problem, we perform a data analysis to investigate the major drivers of physician productivity using patient visit data from our partner ED, and we find that the individual physician, shift hour, and shift type (e.g., day or night) are the determining factors of ED productivity. A simulation study calibrated using real data shows that the new scheduling method can reduce patient wait times by as much as 13% compared to the current scheduling system at our study ED. We also demonstrate how to incorporate physician preference in scheduling through physician clustering based on productivity. Our simulation results show that EDs can receive almost the full benefit of the new scheduling method even when the number of clusters is small.
Investigation of Shale Permeability Evolution considering Bivalued Effective Stress Coefficients for CO2 Injection
Authors: Wang Yi , Wang Hao , Qi Shangyi , Liu Shimin , Zhao Yixin , Yue Wenting
Published: October 2021

Because of the existence of multiscale pores from nano- to macroscale, a multimechanistic shale gas flow process involving the Darcy and Knudsen flows occurs during gas shale well depletion. The respective contribution of the Darcy and Knudsen flows to the permeability is constantly changing with pressure evolution. In this study, laboratory measurements of shale permeability with CO2 injections were carried out under hydrostatic conditions, using the transient pulse-decay method. The “U”-shape permeability curve resulted in both positive and negative effective stress coefficients (Biot’s coefficient)

χ

. A permeability turning point was thus created to partition permeability curves into the Darcy and Knudsen sections. The Knudsen effect was proven to be significant at low pressure/late time in the laboratory. Effective stress and sorption-induced deformation have been found to govern the Darcy permeability evolution under the tested experimental conditions. Thus, negative effective stress coefficients, together with the positive ones, should be applied to a nonmonotonic pressure-permeability evolution to explain the concurrent effect of the Darcy flow and Knudsen flow at different pore pressures.
Investigation on the CBM Extraction Techniques in the Broken-Soft and Low-Permeability Coal Seams in Zhaozhuang Coalmine
Authors: Chen Zhaoying , Fu Xuehai , Li Guofu , Shen Jian , Tian Qingling , Cheng Ming , Wang Yue
Published: October 2021

To enhance the coalbed methane (CBM) extraction in broken-soft coal seams, a method of drilling a horizontal well along the roof to hydraulically fracture the coal seam is studied (i.e., HWR-HFC method). We first tested the physical and mechanical properties of the broken-soft and low-permeability (BSLP) coal resourced from Zhaozhuang coalmine. Afterward, the in situ hydraulic fracturing test was conducted in the No. 3 coal seam of Zhaozhuang coalmine. The results show that (1) the top part of the coal seam is fractured coal, and the bottom is fragmented-mylonitic coal with a firmness coefficient value of less than 1.0. (2) In the hydraulic fracturing test of the layered rock-coal specimens in laboratory, the through-type vertical fractures are usually formed if the applied vertical stress is the maximum principal stress and is greater than 4 MPa compared with the maximum horizontal stress. However, horizontal fractures always developed when horizontal stress is the maximum or it is less than 4 MPa compared with vertical stress. (3) The in situ HWR-HFC hydraulic fracturing tests show that the detected maximum daily gas production is 11,000 m3, and the average gas production is about 7000 m3 per day. This implies that the CBM extraction using this method is increased by 50%~100% compared with traditional hydraulic fracturing in BSLP coal seams. The research result could give an indication of CBM developing in the broken-soft and low-permeability coal seams.
Improving SERS Sensing Efficiency and Catalytic Reduction Activity in Multifunctional Ternary Ag-TiO2-GO Nanostructures: Roles of Electron Transfer Process on Performance Enhancement
Authors: Doan Mai Quan , Anh Nguyen Ha , Van Tuan Hoang , Tu Nguyen Cong , Lam Nguyen Huu , Khi Nguyen Tien , Phan Vu Ngoc , Thang Pham Duc , Le Anh-Tuan
Published: October 2021

Multifunctional nanocomposites have received great attention for years; electron transfer (ET) is considered as an explanatory mechanism for enhancement of performance of these nanostructures. The existence of this ET process has been proved in many studies using either experimental or computational approaches. In this study, a ternary nanocomposite system of Ag/TiO2/GO was prepared to evaluate the performance enhancement in two experimental models: a physical model (i.e., surface-enhanced Raman scattering (SERS) sensor) and a chemical one (i.e., catalytic reduction reaction). The metal/semiconductor heterojunction between Ag and TiO2, as well as Ti-O-C bonds, has allowed plasmonic hot electrons to be transferred in the internal structure of the material. An investigation on the role of Ag content on the SERS sensing and catalytic reduction efficiency of Ag/TiO2/GO was performed in both models. Interestingly, they all resulted in the same optimal Ag content of 50 wt%. It was then further discussed to provide a convincing evidence for the plasmon-induced electron transfer phenomena in the Ag/TiO2/GO nanostructure. These findings also suggest a pathway to design and develop high-performance, cost-effective, facile-preparation, and eco-friendly multifunctional nanostructures for detecting and removing contaminants in environment.
Measuring Performance of Ratio-Exponential-Log Type General Class of Estimators Using Two Auxiliary Variables
Authors: Shabbir Javid , Ahmed Shakeel , Sanaullah Aamir , Onyango Ronald
Published: October 2021

In this paper, a ratio-exponential-log type general class of estimators is proposed in estimating the finite population mean using two auxiliary variables when population parameters of the auxiliary variables are known. From the proposed estimator, some special estimators are identified as members of the proposed general class of estimators. The mean square error (MSE) expressions are obtained up to the first order of approximation. This study finds that the proposed general class of estimators outperforms as compared to the conventional mean estimator, usual ratio estimators, exponential-ratio estimators, log-ratio type estimators, and many other competitor regression type estimators. Four real-life applications are used for efficiency comparison.
Steroid Hormone Exposure as a Potential Hazard in Milk Consumers: A Significant Health Challenge in Iran
Authors: Nili-Ahmadabadi Amir , Rezaei Fatemeh , Heshmati Ali , Ranjbar Akram , Larki-Harchegani Amir
Published: October 2021

The presence of steroid hormones in milk is inevitable, and they can be considered as potential carcinogenic agents for consumers. The purpose of this study was to evaluate the level of 17β-estradiol, progesterone, and hydroxyprogesterone in sixty-nine bovine milk samples, collected from April to September 2020, in Hamadan, Iran. The milk samples were analyzed using enzyme-linked immunosorbent assay (ELISA). In this study, the mean contents of 17β-estradiol, progesterone, and hydroxyprogesterone in the milk samples were determined to be 330.5 ± 190.2 pg/ml, 3.57 ± 2.47 ng/ml, and 1.54 ± 0.41 ng/ml, respectively. However, the content of these steroid hormones in milk samples could be considered safe in children and adults, if the milk consumption is assumed to be in the reported range (175–240 ml/daily). Due to the effects of steroid hormones, especially 17β-estradiol, in the etiology of various cancers, regular monitoring of these hormones is recommended in milk and its dairy products in Iran.
M-Polynomials and Associated Topological Indices of Sodalite Materials
Authors: Abbas Ghazanfar , Ibrahim Muhammad , Ahmad Ali , Azeem Muhammad , Elahi Kashif
Published: October 2021

Natural zeolites are commonly described as macromolecular sieves. Zeolite networks are very trendy chemical networks due to their low-cost implementation. Sodalite network is one of the most studied types of zeolite networks. It helps in the removal of greenhouse gases. To study this rich network, we use an authentic mathematical tool known as M-polynomials of the topological index and show some physical and chemical properties in numerical form, and to understand the structure deeply, we compare different legitimate M-polynomials of topological indices, concluding in the form of graphical comparisons.
Evaluation of the Influence of Antistripping Agents on Water Sensitivity of the Stone Matrix Asphalt Mixture Modified by Recycled Ground Tire Rubber and Waste Polyethylene Terephthalate
Authors: Ameli Alireza , Babagoli Rezvan
Published: October 2021

This research intends to evaluate the effects of the waste polyethylene terephthalate (PET), antistripping agents (ASA), and ground tire rubber (GTR) on the performance properties of the stone matrix asphalt (SMA) mix binder/water damage resistance. Liquid antistripping agents, added to 85/100 penetration grade binder to evaluate the ASA effects, were A (M500), B (EvothermM1), and C (LOF‐6500). Tests conducted to study the modified bitumen’s rheological properties included softening point, penetration, rotational viscosity (RV), and dynamic shear rheometer (DSR), and tests performed in order to examine the moisture sensitivity of the modified mix were the Texas boiling and resilient modulus (MR), fracture energy (FE), and indirect tensile strength (ITS) ratio tests. Results showed that the MR, ITS, and FE of asphalt mixes modified with crumb rubber (CR), ASA, and PET were improved. Adding 50% PET, 50% CR, and ASA (B) led to the highest tensile strength, resilient modulus, and fracture energy ratios showing a perfect water susceptibility of the mentioned mix.
Machine Learning-Based Ensemble Model for Zika Virus T-Cell Epitope Prediction
Authors: Bukhari Syed Nisar Hussain , Jain Amit , Haq Ehtishamul , Khder Moaiad Ahmad , Neware Rahul , Bhola Jyoti , Lari Najafi Moslem
Published: October 2021

Zika virus (ZIKV), the causative agent of Zika fever in humans, is an RNA virus that belongs to the genus Flavivirus. Currently, there is no approved vaccine for clinical use to combat the ZIKV infection and contain the epidemic. Epitope-based peptide vaccines have a large untapped potential for boosting vaccination safety, cross-reactivity, and immunogenicity. Though many attempts have been made to develop vaccines for ZIKV, none of these have proved to be successful. Epitope-based peptide vaccines can act as powerful alternatives to conventional vaccines due to their low production cost, less reactogenic, and allergenic responses. For designing an effective and viable epitope-based peptide vaccine against this deadly virus, it is essential to select the antigenic T-cell epitopes since epitope-based vaccines are considered safe. The in silico machine-learning-based approach for ZIKV T-cell epitope prediction would save a lot of physical experimental time and efforts for speedy vaccine development compared to in vivo approaches. We hereby have trained a machine-learning-based computational model to predict novel ZIKV T-cell epitopes by employing physicochemical properties of amino acids. The proposed ensemble model based on a voting mechanism works by blending the predictions for each class (epitope or nonepitope) from each base classifier. Predictions obtained for each class by the individual classifier are summed up, and the class with the majority vote is predicted upon. An odd number of classifiers have been used to avoid the occurrence of ties in the voting. Experimentally determined ZIKV peptide sequences data set was collected from Immune Epitope Database and Analysis Resource (IEDB) repository. The data set consists of 3,519 sequences, of which 1,762 are epitopes and 1,757 are nonepitopes. The length of sequences ranges from 6 to 30 meter. For each sequence, we extracted 13 physicochemical features. The proposed ensemble model achieved sensitivity, specificity, Gini coefficient, AUC, precision, F-score, and accuracy of 0.976, 0.959, 0.993, 0.994, 0.989, 0.985, and 97.13%, respectively. To check the consistency of the model, we carried out five-fold cross-validation and an average accuracy of 96.072% is reported. Finally, a comparative analysis of the proposed model with existing methods has been carried out using a separate validation data set, suggesting the proposed ensemble model as a better model. The proposed ensemble model will help predict novel ZIKV vaccine candidates to save lives globally and prevent future epidemic-scale outbreaks.
On the Sensitivity of the Simulated Diurnal Cycle of Precipitation to 3-Hourly Radiosonde Assimilation: A Case Study over the Western Maritime Continent
Authors: Kwang Lee Joshua Chun , Dipankar Anurag , Huang Xiang-Yu
Published: October 2021

The diurnal cycle is the most prominent mode of rainfall variability in the tropics, governed mainly by the strong solar heating and land–sea interactions that trigger convection. Over the western Maritime Continent, complex orographic and coastal effects can also play an important role. Weather and climate models often struggle to represent these physical processes, resulting in substantial model biases in simulations over the region. For numerical weather prediction, these biases manifest themselves in the initial conditions, leading to phase and amplitude errors in the diurnal cycle of precipitation. Using a tropical convective-scale data assimilation system, we assimilate 3-hourly radiosonde data from the pilot field campaign of the Years of Maritime Continent, in addition to existing available observations, to diagnose the model biases and assess the relative impacts of the additional wind, temperature, and moisture information on the simulated diurnal cycle of precipitation over the western coast of Sumatra. We show how assimilating such high-frequency in situ observations can improve the simulated diurnal cycle, verified against satellite-derived precipitation, radar-derived precipitation, and rain gauge data. The improvements are due to a better representation of the sea breeze and increased available moisture in the lowest 4 km prior to peak convection. Assimilating wind information alone was sufficient to improve the simulations. We also highlight how during the assimilation, certain multivariate background error constraints and moisture addition in an ad hoc manner can negatively impact the simulations. Other approaches should be explored to better exploit information from such high-frequency observations over this region.
Genomic analysis of the nomenclatural type strain of the nematode-associated entomopathogenic bacterium Providencia vermicola
Authors: Andolfo Giuseppe , Schuster Christina , Gharsa Haifa Ben , Ruocco Michelina , Leclerque Andreas
Published: October 2021

Background

Enterobacteria of the genus Providencia are mainly known as opportunistic human pathogens but have been isolated from highly diverse natural environments. The species Providencia vermicola comprises insect pathogenic bacteria carried by entomoparasitic nematodes and is investigated as a possible insect biocontrol agent. The recent publication of several genome sequences from bacteria assigned to this species has given rise to inconsistent preliminary results.

Results

The genome of the nematode-derived P. vermicola type strain DSM_17385 has been assembled into a 4.2 Mb sequence comprising 5 scaffolds and 13 contigs. A total of 3969 protein-encoding genes were identified. Multilocus sequence typing with different marker sets revealed that none of the previously published presumed P. vermicola genomes represents this taxonomic species. Comparative genomic analysis has confirmed a close phylogenetic relationship of P. vermicola to the P. rettgeri species complex. P. vermicola DSM_17385 carries a type III secretion system (T3SS-1) with probable function in host cell invasion or intracellular survival. Potentially antibiotic resistance-associated genes comprising numerous efflux pumps and point-mutated house-keeping genes, have been identified across the P. vermicola genome. A single small (3.7 kb) plasmid identified, pPVER1, structurally belongs to the qnrD-type family of fluoroquinolone resistance conferring plasmids that is prominent in Providencia and Proteus bacteria, but lacks the qnrD resistance gene.

Conclusions

The sequence reported represents the first well-supported published genome for the taxonomic species P. vermicola to be used as reference in further comparative genomics studies on Providencia bacteria. Due to a striking difference in the type of injectisome encoded by the respective genomes, P. vermicola might operate a fundamentally different mechanism of entomopathogenicity when compared to insect-pathogenic Providencia sneebia or Providencia burhodogranariea. The complete absence of antibiotic resistance gene carrying plasmids or mobile genetic elements as those causing multi drug resistance phenomena in clinical Providencia strains, is consistent with the invertebrate pathogen P. vermicola being in its natural environment efficiently excluded from the propagation routes of multidrug resistance (MDR) carrying genetic elements operating between human pathogens. Susceptibility to MDR plasmid acquisition will likely become a major criterion in the evaluation of P. vermicola for potential applications in biological pest control.
Cell type-specific potential pathogenic genes and functional pathways in Alzheimer’s Disease
Authors: Wang Xiao-Lan , Li Lianjian
Published: October 2021

Background

Alzheimer's disease (AD) is a pervasive age-related and highly heritable neurodegenerative disorder but has no effective therapy. The complex cellular microenvironment in the AD brain impedes our understanding of pathogenesis. Thus, a comprehensive investigation of cell type-specific responses in AD is crucial to provide precise molecular and cellular targets for therapeutic development.

Methods

Here, we integrated analyzed 4,441 differentially expressed genes (DEGs) that were identified from 263,370 single-cells in cortex samples by single-nucleus RNA sequencing (snRNA-seq) between 42 AD-pathology subjects and 39 normal controls within 3 studies. DEGs were analyzed in microglia, astrocytes, oligodendrocytes, excitatory neurons, inhibitory neurons, and endothelial cells, respectively. In each cell type, we identified both common DEGs which were observed in all 3 studies, and overlapping DEGs which have been seen in at least 2 studies. Firstly, we showed the common DEGs expression and explained the biological functions by comparing with existing literature or multil-omics signaling pathways knowledgebase. We then determined the significant modules and hub genes, and explored the biological processes using the overlapping DEGs. Finally, we identified the common and distinct dysregulated pathways using overall DEGs and overlapping DEGs in a cell type-specific manner.

Results

Up-regulated LINGO1 has been seen in both oligodendrocytes and excitatory neurons across 3 studies. Interestingly, genes enriched in the mitochondrial module were up-regulated across all cell types, which indicates mitochondrial dysfunction in the AD brain. The estrogen signaling pathway seems to be the most common pathway that is disrupted in AD.

Conclusion

Together, these analyses provide detailed information of cell type-specific and overall transcriptional changes and pathways underlying the human AD-pathology. These findings may provide important insights for drug development to tackle this disease.