bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ixodid Tick Dissection and Tick Ex Vivo Organ Cultures for Tick‐Borne Virus Research
Authors: Grabowski Jeffrey M. , Kissinger Ryan 
Published: October 2020

AbstractTick‐borne viruses cause thousands of cases of disease worldwide every year. Specific countermeasures to many tick‐borne viruses are not commercially available. Very little is known regarding tick‐virus interactions and increasing this knowledge can lead to potential targets for countermeasure development. Virus infection of ex vivo organ cultures from ticks can provide an approach to identify susceptible cell types of tissue to infection. Additionally, these organ cultures can be used for functional genomic studies to pinpoint tick‐specific genes involved in the virus lifecycle. Provided here are step‐by‐step procedures to set up basic tick organ cultures in combination with virus infection and/or functional genomic studies. These procedures can be adapted for future use to characterize other tick‐borne pathogen infections as well as tick‐specific biological processes. © 2020 Wiley Periodicals LLC.Basic Protocol 1: Loading 96‐well plates with gelfoam substrateBasic Protocol 2: Step‐by‐step aseptic dissection of unfed female/male Ixodes scapularis ticks for multiple organsBasic Protocol 3: Step‐by‐step aseptic dissection of fed female Ixodes scapularis ticks to remove salivary glandsBasic Protocol 4: Metabolic viability analyses of tick organ culturesBasic Protocol 5: Virus infection of tick organ culturesBasic Protocol 6: Functional RNA interference analyses using tick organ cultures
March of Mycobacterium: miRNAs intercept host cell CD40 signalling
Authors: Chauhan Prashant , Dandapat Jagneshwar , Sarkar Arup , Saha Bhaskar 
Published: October 2020

AbstractThe disease tuberculosis is fatal if untreated. It is caused by the acid‐fast bacilli Mycobacterium tuberculosis. Mycobacterium resides and replicates within the alveolar macrophages, causing inflammation and granuloma, wherein macrophage‐T cell interactions enhance the inflammation‐causing pulmonary caseous lesions. The first interactions between Mycobacterium and the receptors on macrophages decide the fate of Mycobacterium because of phagolysosomal impairments and the expression of several miRNAs, which may regulate CD40 expression on macrophages. While the altered phagolysosomal functions impede antigen presentation to the T cell‐expressed antigen receptor, the interactions between the macrophage‐expressed CD40 and the T cell‐expressed CD40‐ligand (CD40L or CD154) provide signals to T cells and Mycobacterium‐infected macrophages. These two functions significantly influence the resolution or persistence of Mycobacterium infection. CD40 controls T‐cell polarisation and host‐protective immunity by eliciting interleukin‐12p40, nitric oxide, reactive oxygen species and IFN‐γ production. Indeed, CD40‐deficient mice succumb to low‐dose aerosol infection with Mycobacterium because of deficient interleukin (IL)‐12 production leading to impaired IFN‐γ‐secreting T‐cell response. In contrast, despite generating fewer granulomas, the CD40L‐deficient mice developed anti‐mycobacterial T‐cell responses to the levels observed in the wild‐type mice. These host‐protective responses are significantly subdued by the Mycobacterium‐infected macrophage produced TGF‐β and IL‐10, which promote pro‐mycobacterial T‐cell responses. The CD40‐CD40L‐induced counteractive immune responses against Mycobacterium thus present a conundrum that we explain here with a reconciliatory hypothesis. Experimental validation of the hypothesis will provide a rationale for designing anti‐tubercular immunotherapy.
Kinetics and isotype assessment of antibodies targeting the spike protein receptor‐binding domain of severe acute respiratory syndrome‐coronavirus‐2 in COVID‐19 patients as a function of age, biological sex and disease severity
Authors: Graham Nancy R , Whitaker Annalis N , Strother Camilla A , Miles Ashley K , Grier Dore , McElvany Benjamin D , Bruce Emily A , Poynter Matthew E , Pierce Kristen K , Kirkpatrick Beth D , Stapleton Renee D , An Gary , van den Broek‐Altenburg Eline , Botten Jason W , Crothers Jessica W , Diehl Sean A 
Published: October 2020

AbstractObjectivesThere is an incomplete understanding of the host humoral immune response to severe acute respiratory syndrome (SARS)‐coronavirus (CoV)‐2, which underlies COVID‐19, during acute infection. Host factors such as age and sex as well as the kinetics and functionality of antibody responses are important factors to consider as vaccine development proceeds. The receptor‐binding domain of the CoV spike (RBD‐S) protein mediates host cell binding and infection and is a major target for vaccine design to elicit neutralising antibodies.MethodsWe assessed serum anti‐SARS‐CoV‐2 RBD‐S IgG, IgM and IgA antibodies by a two‐step ELISA and neutralising antibodies in a cross‐sectional study of hospitalised COVID‐19 patients of varying disease severities. Anti‐RBD‐S IgG levels were also determined in asymptomatic seropositives.ResultsWe found equivalent levels of anti‐RBD‐S antibodies in male and female patients and no age‐related deficiencies even out to 93 years of age. The anti‐RBD‐S response was evident as little as 6 days after onset of symptoms and for at least 5 weeks after symptom onset. Anti‐RBD‐S IgG, IgM and IgA responses were simultaneously induced within 10 days after onset, with anti‐RBD‐S IgG sustained over a 5‐week period. Anti‐RBD‐S antibodies strongly correlated with neutralising activity. Lastly, anti‐RBD‐S IgG responses were higher in symptomatic COVID‐19 patients during acute infection compared with asymptomatic seropositive donors.ConclusionOur results suggest that anti‐RBD‐S IgG reflect functional immune responses to SARS‐CoV‐2, but do not completely explain age‐ and sex‐related disparities in COVID‐19 fatalities.
Simultaneous Detection of Paracetamol, Ascorbic Acid, and Caffeine Using a Bismuth–Silver Nanosensor
Authors: van der Horst Charlton , Silwana Bongiwe , Gil Eric , Iwuoha Emmanuel , Somerset Vernon 
Published: October 2020

AbstractThe bimetallic nanoparticles of bismuth‐silver were used to modify a disk GCE for the simultaneous electrochemical analysis of caffeine (CAF), ascorbic acid (AA), and paracetamol (PAR). The constructed Bi‐AgNPs/GCE illustrated strong electrocatalytic activity towards the oxidation of CAF, PAR, and AA. Under the optimum conditions, the sensor provided linearity for PAR, AA, CAF between 2 to 20 μΜ, 10 to 70 μM, and 2 to 40 μM (n=3), respectively. The detection limits for CAF, PAR, and AA was 2.36 μM, 0.155 μM, and 0.697 μM, respectively. The GCE/Bi‐AgNPs sensor presented good sensitivity and selectivity for the simultaneous electrochemical analysis of CAF, PAR, and AA.
Activated Carbon Derived from Rice Husk as Efficient Oxygen Reduction Catalyst in Microbial Fuel Cell
Authors: Jiao Yongli , Hu Youshuang , Han Lujie , Zhou Minghua 
Published: October 2020

AbstractIn microbial fuel cells (MFCs), an important factor limiting practical applications is the high catalyst cost in cathode. Herein a rice husk‐based porous carbon made through hydrolysis, activation and rolling was used as novel cathode. These porous carbons were characterized by SEM, XPS and BET analysis, and electrochemical measurements including linear sweep voltammetry and Tafel test were investigated. A maximum powder density (317.7±0.4 mW m−2) on AC‐KOH‐1h with the largest BET surface area of 1809 m2 g−1 was obtained. This study revealed a fresh territory about the application of porous carbon produced by renewable resources for MFC electrode.
Conversion of Landsat 8 multispectral data through modified private content‐based image retrieval technique for secure transmission and privacy
Authors: Shakya Amit K. , Ramola Ayushman , Vidyarthi Anurag 
Published: October 2020

AbstractIn this research work, we have developed a new image encryption‐based algorithm for Landsat 8 satellite images. Image statistical parameters related to first‐order image statistics, that is, mean (μ), SD (σ), and variance (σ2) are used to obtain the feature values for both original images and their encrypted versions. Multispectral satellite images generally contain a wide range of bands, which is 9 to 11 specifically for the Landsat 8 satellite. Hence, the information content of these images is richer than typical images. Through this algorithm, we aim to reduce the image content by randomly selecting only 10% of the total image pixels. These pixels are used to create new images, the so‐called encrypted images. The visual presentation of the encrypted image resembles a noisy picture. First‐order image statistics are calculated for both original images and their encrypted counterparts. These parameters show a similarity in their numerical values for both original and encrypted images. Thus, noisy pictures can be used for transmission in place of the original image when an outcome is decided through statistical image features. The visual similarity in the original images and encrypted images is obtained from the histogram signature plot for both original and encrypted images. The proposed algorithm can hence be used to convert image data for secure transmission and privacy.
Variation in cancer risk among families with genetic susceptibility
Authors: Huang Theodore , Braun Danielle , Lynch Henry T. , Parmigiani Giovanni 
Published: October 2020

AbstractGermline mutations in many genes have been shown to increase the risk of developing cancer. This risk can vary across families who carry mutations in the same gene due to differences in the specific variants, gene–gene interactions, other susceptibility mutations, environmental factors, and behavioral factors. We develop an analytic tool to explore this heterogeneity using family history data. We propose to evaluate the ratio between the number of observed cancer cases in a family and the number of expected cases under a model where risk is assumed to be the same across families. We perform this analysis for both carriers and noncarriers in each family, using carrier probabilities when carrier statuses are unknown, and visualize the results. We first illustrate the approach in simulated data and then apply it to data on colorectal cancer risk in families carrying mutations in Lynch syndrome genes from Creighton University's Hereditary Cancer Center. We show that colorectal cancer risk in carriers can vary widely across families, and that this variation is not matched by a corresponding variation in the noncarriers from the same families. This suggests that the sources of variation in these families are to be found predominantly in variants harbored in the mutated MMR genes considered, or in variants interacting with them.
The neural basis for mental state attribution: A voxel‐based lesion mapping study
Authors: Cohen‐Zimerman Shira , Khilwani Harsh , Smith Gretchen N. L. , Krueger Frank , Gordon Barry , Grafman Jordan 
Published: October 2020

AbstractThe ability to infer other persons' mental states, “Theory of Mind” (ToM), is a key function of social cognition and is needed when interpreting the intention of others. ToM is associated with a network of functionally related regions, with reportedly key prominent hubs located in the dorsolateral prefrontal cortex (dlPFC) and the temporoparietal junction (TPJ). The involvement of (mainly the right) TPJ in ToM is based primarily on functional imaging studies that provide correlational evidence for brain‐behavior associations. In this lesion study, we test whether certain brain areas are necessary for intact ToM performance. We investigated individuals with penetrating traumatic brain injury (n = 170) and healthy matched controls (n = 30) using voxel‐based lesion‐symptom mapping (VLSM) and by measuring the impact of a given lesion on white matter disconnections. ToM performance was compared between five patient groups based on lesion location: right TPJ, left TPJ, right dlPFC, left dlPFC, and other lesion, as well as healthy controls. The only group to present with lower ToM abilities was the one with lesions in the right dlPFC. Similarly, VLSM analysis revealed a main cluster in the right frontal middle gyrus and a secondary cluster in the left inferior parietal gyrus. Last, we found that disconnection of the left inferior longitudinal fasciculus and right superior longitudinal fasciculus were associated with poor ToM performance. This study highlights the importance of lesion studies in complementing functional neuroimaging findings and supports the assertion that the right dlPFC is a key region mediating mental state attribution.
Effects of repeated menstrual pain on empathic neural responses in women with primary dysmenorrhea across the menstrual cycle
Authors: Wang Chen , Liu Yang , Dun Wanghuan , Zhang Tian , Yang Jing , Wang Ke , Mu Junya , Zhang Ming , Liu Jixin 
Published: October 2020

AbstractPrimary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex‐hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task‐based functional magnetic resonance imaging (fMRI). Fifty‐seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post‐hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain‐free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain.
Rule‐based Verification of System Security using Feature‐Based Product Line Engineering
Authors: Teaff James K. 
Published: October 2020

ABSTRACTSystems security engineering is a discipline to engineer a system of interest ensuring system functionality under disruptive conditions associated with misuse and malicious behavior. Today's cyber‐physical systems must survive in a constantly changing threat environment. Cybersecurity controls and cyber resiliency capabilities require continuous delivery to meet this challenge. This article describes creating and using a rule base as an integral part of a systems and software product line engineering (PLE) factory enabling continuous resilient and secure cyber‐physical systems delivery ensuring the system can function under disruptive conditions. A hypothetical intelligence gathering network comprising unmanned vehicles, a ground control segment, and an intelligence analytics segment is the system of interest. Systems engineering activities include continuously analyzing the cyber‐attack surface for each system variant in the product portfolio; creating or amending cyber resiliency capabilities and cybersecurity controls for each system variant addressing each attack vector; and a living rule base maintained within a PLE factory ensuring each system variant automatically generated by the factory contains the requisite system capabilities. Applying this approach results in rule‐based verification of continuously delivered cyber resiliency capabilities and cybersecurity controls for each fielded system variant. Moving at the speed of mission need is essential, and automated rule‐based verification of system deliveries meets that need.
Leveraging a System Model to Initiate Security Architecture Development for Product Lines
Authors: Agrawal Angel 
Published: October 2020

ABSTRACTThis paper presents a method for leveraging Model Based Systems Engineering to facilitate systems security architecture development, with product line engineering considerations. The sensitivity of systems security information constrains the development of the system security model. Creating a tailored subset of the system of interest (SOI) model can generate value as a system security decision driver, and serve as the cornerstone for system security model development. This establishes clear correlation points between the SOI model and system security model. Conducting this collaboration early in the SOI lifecycle enables engineers to implement security considerations in the system design, reducing the cost and schedule impact of delaying system security development. For product line systems, common features are quickly identified with their associated security considerations. Variants retain these common features, preventing rework.
Modelling infiltration rates in permeable stormwater channels using soft computing techniques*
Authors: Yaseen Zaher Mundher , Sihag Parveen , Yusuf Badronnisa , Al‐Janabi Ahmed Mohammed Sami 
Published: October 2020

AbstractIn the design of permeable stormwater channels, the ability to quantify infiltration rates accurately is important for assessing the capability of such channels to perform their required functions. Most of the available infiltration models neglect the effects of water level and channel section on the infiltration rate. In this study, physical channel models, with different channel sections, were developed in the laboratory and used to measure the infiltration rates. The performance of three soft computing techniques, including Gaussian process regression, M5P, and random forest (RF) models, were evaluated against measured values. Seven independent input variables, namely, channel side slope (m), base width (b), water level (y), sand (%), silt (%), clay (%), and time (T) and the output variable infiltration rate (f(t)), were considered in the model development and validation. The Gaussian progression–Pearson VII universal kernel function model approach was found to perform best for the data set considered, followed by the RF‐based model. The sensitivity investigation showed that time, water level, and channel side slope were the most influential input variables in predicting infiltration rates for permeable stormwater channels and should be given primary consideration in designing such channels. © 2020 John Wiley & Sons, Ltd.
Activation of forkhead box O3a by mono(2‐ethylhexyl)phthalate and its role in protection against mono(2‐ethylhexyl)phthalate‐induced oxidative stress and apoptosis in human cardiomyocytes
Authors: Wang Zeze , Liu Yi , Liu Xuehui , Zhou Lixiao , Ma Xindi , Liu Junyao , Wang Lei , Guo Huicai 
Published: October 2020

AbstractMono(2‐ethylhexyl)phthalate (MEHP), the active metabolite of di(2‐ethylhexyl)phthalate (DEHP), is known to exert cardiotoxicity. The aim of the present study was to investigate the role of forkhead box O3a (FOXO3a) in MEHP‐induced human AC16 cardiomyocyte injuries. MEHP reduced cell viability and mitochondrial membrane potential (ΔΨm), whereas it increased lactate dehydrogenase (LDH) leakage, production of reactive oxygen species (ROS), and apoptosis in cardiomyocytes. The expression of FOXO3a and its target genes, mitochondrial superoxide dismutase (Mn‐SOD) and apoptosis repressor with caspase recruitment domain (ARC), increased after MEHP exposure, but the expression of p‐FOXO3a protein was decreased. Overexpression of FOXO3a decreased the production of ROS and the apoptosis rate induced by MEHP, and the expression of Mn‐SOD and ARC was further increased after MEHP exposure. In contrast, knockdown of FOXO3a resulted in increased ROS production and apoptosis and suppressed the expression of Mn‐SOD and ARC in the presence of MEHP. However, overexpression or knockdown of FOXO3a did not affect MEHP‐induced loss of ΔΨm. In conclusion, the loss of ΔΨm and apoptosis are involved in MEHP‐induced cardiomyocyte toxicity. Activation of FOXO3a defends against MEHP‐induced oxidative stress and apoptosis by upregulating the expression of Mn‐SOD and ARC in AC16 cardiomyocytes.
Atomistic detailed free‐energy landscape of intrinsically disordered protein studied by multi‐scale divide‐and‐conquer molecular dynamics simulation
Authors: Shimoyama Hiromitsu , Yonezawa Yasushige 
Published: October 2020

AbstractCalcineurin (CaN) is a eukaryotic serine/threonine protein phosphatase activated by both Ca2+ and calmodulin (CaM), including intrinsically disordered region (IDR). The region undergoes folding into an α‐helix form in the presence Ca2+‐loaded CaM. To sample the ordered structure of the IDR by conventional all atom model (AAM) molecular dynamics (MD) simulation, the IDR and Ca2+‐loaded CaM must be simultaneously treated. However, it is time‐consuming task because the coupled folding and binding should include repeated binding and dissociation. Then, in this study, we propose novel multi‐scale divide‐and‐conquer MD (MSDC‐MD), which combines AAM‐MD and coarse‐grained model MD (CGM‐MD). To speed up the conformation sampling, MSDC‐MD simulation first treats the IDR by CGM to sample conformations from wide conformation space; then, multiple AAM‐MD in a limited area is initiated using the resultant CGM conformation, which is reconstructed by homology modeling method. To investigate performance, we sampled the ordered conformation of the IDR using MSDC‐MD; the root‐mean‐square distance (RMSD) with respect to the experimental structure was 2.23 Å.
Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation
Authors: Commander Sarah Jane , Wu Huali , Boakye‐Agyeman Felix , Melloni Chiara , Hornik Chi Dang , Zimmerman Kanecia , Al‐Uzri Amira , Mendley Susan R. , Harper Barrie , Cohen‐Wolkowiez Michael , Hornik Christoph P. ,   the Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee
Published: October 2020

AbstractHydrochlorothiazide (HCTZ) is a thiazide diuretic used in adults and children for the treatment of hypertension and edema. The pharmacokinetic (PK) properties of HCTZ in children are not well characterized, particularly among children with obesity who frequently suffer from hypertension and may, therefore, benefit from HCTZ therapy. HCTZ is excreted in the kidney via organic anion transporters 1 and 3 (OAT1 and OAT3). The ontogeny of OAT1 and OAT3 remain unknown, but HCTZ clearance may serve as a surrogate marker of OAT1 and OAT3 maturation. Population PK modeling was performed in NONMEM, and the model was leveraged to conduct dose‐exposure simulations. This study examined 83 plasma samples from 49 participants (69% male) taking enteral HCTZ. The median (range) postnatal age was 6.7 years (0.03‐19.5 years), and 17 (34%) participants were obese or morbidly obese. The median (range) dose of HCTZ was 0.654 mg/kg (0.11‐1.8 kg) and the median number of doses recorded per participant was 5 (1‐8). HCTZ PK was well characterized by a 1‐compartment PK model. Body weight and a maturation model based on postmenstrual age were significant covariates for apparent clearance, but the presence of obesity was not. Dosing simulations were performed with a standardized 1mg/kg. Simulated exposure (area under the curve and maximum HCTZ concentrations) decreased with age and was likely due to older children receiving the maximum absolute doses of HCTZ. Further studies with more patients in each age group are required to confirm these PK findings of HCTZ in the children.