Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis and Electrospinning of Polycaprolactone from an Aluminium-Based Catalyst: Influence of the Ancillary Ligand and Initiators on Catalytic Efficiency and Fibre Structure

In the present study, we investigated the catalytic performance of a 2,2′-methylenebis(6-tert-butyl-4-methylphenol) (MDBP)–aluminium complex for the ring-opening polymerisation (ROP) of ε-caprolactone in combination with various alcohols as initiators. Three different alcohols were investigated: 1-adamantanemethanol (A), 1H,1H,2H,2H-perfluoro-1-octanol (F) and isopropanol (I). Samplings of polycaprolactone (PCL) at various reaction times showed a linear increase in the polymer molecular weight with time, with very narrow polydispersity, confirming the living nature of the catalytic system. Scanning electron microscope (SEM) images of electrospun PCL fibre mats produced from 30 wt % dichloromethane/dimethyl sulfoxide solutions showed a high level of surface porosity with a reasonable homogeneity of fibre diameters. The values of the liquid absorption and water contact angle were measured for the electrospun mats, with the F-capped PCL consistently showing absorption values up to three times higher than those of PCL samples capped with the other two alcohols, as well as increased hydrophobicity. The nature of the alcohol can influence the surface hydrophobicity and absorption ability of electrospun fibres, demonstrating the possibility of tailoring material properties through controlled polymerisation.
In Vivo Biocompatibility of Electrospun Biodegradable Dual Carrier (Antibiotic + Growth Factor) in a Mouse Model—Implications for Rapid Wound Healing

Tissue engineering technologies involving growth factors have produced one of the most advanced generations of diabetic wound healing solutions. Using this approach, a nanocomposite carrier was designed using Poly(d,l-lactide-co-glycolide) (PLGA)/Gelatin polymer solutions for the simultaneous release of recombinant human epidermal growth factor (rhEGF) and gentamicin sulfate at the wound site to hasten the process of diabetic wound healing and inactivation of bacterial growth. The physicochemical characterization of the fabricated scaffolds was carried out using scanning electron microscopy (SEM) and X-ay diffraction (XRD). The scaffolds were analyzed for thermal stability using thermogravimetric analysis and differential scanning calorimetry. The porosity, biodegradability, and swelling behavior of the scaffolds was also evaluated. Encapsulation efficiency, drug loading capacity, and in vitro drug release were also investigated. Further, the bacterial inhibition percentage and detailed in vivo biocompatibility for wound healing efficiency was performed on diabetic C57BL6 mice with dorsal wounds. The scaffolds exhibited excellent wound healing and continuous proliferation of cells for 12 days. These results support the applicability of such systems in rapid healing of diabetic wounds and ulcers.
Multistep approach to control microbial fouling of historic building materials by aerial phototrophs

Abstract The scientific multistep approach described herein is a result of two years of research into a control method against microbial fouling and biodeterioration of historic building materials by phototrophs. A series of tests were conducted to select the best antifouling agent for eliminating ‘green’ coatings and protecting surfaces against biofouling. Of the seven active compounds, two with the best penetration abilities were subjected to a photosynthetic activity inhibition test using confocal microscopy. Of the two, a quaternary ammonium salt (QAC) – didecyldimethylammonium chloride (DDAC) – was found to be the most effective. Ten biocides containing QACs at different concentrations were then tested against ‘green’ coatings on wood, brick and plaster, with the best four being selected for further research in model conditions. As a result, biocides containing >14% (v v–1) DDAC were found to be successful antifouling agents for protecting historical materials against biodeterioration by phototrophs.
Field-Based Affinity Optimization of a Novel Azabicyclohexane Scaffold HIV-1 Entry Inhibitor

Small-molecule HIV-1 entry inhibitors are an extremely attractive therapeutic modality. We have previously demonstrated that the entry inhibitor class can be optimized by using computational means to identify and extend the chemotypes available. Here we demonstrate unique and differential effects of previously published antiviral compounds on the gross structure of the HIV-1 Env complex, with an azabicyclohexane scaffolded inhibitor having a positive effect on glycoprotein thermostability. We demonstrate that modification of the methyltriazole-azaindole headgroup of these entry inhibitors directly effects the potency of the compounds, and substitution of the methyltriazole with an amine-oxadiazole increases the affinity of the compound 1000-fold over parental by improving the on-rate kinetic parameter. These findings support the continuing exploration of compounds that shift the conformational equilibrium of HIV-1 Env as a novel strategy to improve future inhibitor and vaccine design efforts.
Finite Element Modeling and Simulation of Photoconductive and Ballistic Semiconductor Nanodevices

This thesis presents models, simulation techniques, and simulation results for two types of semiconductor nanodevice; the metal-semiconductor-metal (MSM) photodetector, and the ballistic deflection transistor (BDT). Our simulation tools were developed using the commercial ComsolTM finite element analysis (FEA) field solver to obtain the numeric solutions. Finite element models have been developed for both an alloyedand surfacecontact MSM photodetector. The simulation results agree with previously reported experimental data. The alloyed device, despite having a somewhat larger capacitance, has a non-illuminated region of lower resistance with a more-uniform and deeperpenetrating electric field and carrier transport current. The latter explains, in terms of the equivalent lumped parameters, the experimentally observed faster response of such device. The model was further used to predict improved responsivity, based on electrode spacing and antireflective coating, as well as the optimal depth of the alloyed contact being approximately half of the optical penetration depth. For the BDT, novel simulation techniques, also based on the FEA method, have been developed. The results demonstrate that diffusive transport is capable of predicting the current vs. voltage characteristics of the current-generation of BDTs, as well as the effects of selected changes in the BDT geometry. Simulation results were used to predict the characteristics of several variations of scaled-down and geometrymodified devices and other physical parameters. Also, the newly introduced concept
Effect of Alcohol Intoxication on Bystander Intervention in a Vignette Depiction of Sexual Assault.

OBJECTIVE Alcohol-related sexual violence remains a public health problem. Despite the popularity of sexual assault bystander intervention programs, these may be limited in addressing bystander intoxication because the effects of intoxication on intervening in a sexual assault are unknown. Therefore, we tested the effects of alcohol intoxication on the five steps of bystander intervention in a sexual assault vignette. METHOD Young adults (N = 128; 50% women) were randomly assigned to consume alcohol (target blood alcohol concentration = 0.08%; n = 64) or a nonalcoholic control beverage (n = 64) in a bar-laboratory. Next, participants were presented with a vignette describing events occurring in a convivial drinking context that ends with nonconsensual sexual behavior. Latané and Darley's bystander intervention model steps were assessed in a semistructured interview. RESULTS Participants in the control condition recalled the story more accurately (Step 1: notice the event) and reported greater risk/need for intervention (Step 2), but they did not differ on the latter three steps of bystander intervention compared with alcohol-condition participants. Intoxication effects were similar for men and women. Furthermore, risk/need for intervention (Step 2) partially mediated the effect of alcohol condition on personal responsibility (Step 3) and relative benefits versus costs from intervening (Step 4). CONCLUSIONS Prevention programs should consider the effects of alcohol on detecting a sexual assault and the need to intervene. If intoxicated bystanders do not detect a sexual assault, then bystanders will not reach the crucial steps (i.e., taking responsibility for intervening; willingness and ability to intervene) required to intervene successfully.
Exploring the possibility of combining discrete choice modelling and social networks analysis: an application to the analysis of weather-related uncertainty in long-distance travel behaviour

One deviation from the traditional theory of choice is that individuals, when facing a decision, are affected by the choices and behaviours of others. This discussion paper explores the way that this can be taken into account in discrete choice stated preference (SP) experiments. In particular, the possibility of integrating, to various extents, SP experiments and Social Networks Analysis (SNA) is discussed. Issues relating to social interactions in discrete choice are presented, as drawn from existing literature in economics and transportation. This is supplemented by work in progress on a study which attempts to analyse the way long-distance travellers react to uncertainty caused by extreme weather conditions. Finally, a number of theoretical, practical and empirical challenges are discussed, including the role of respondents reporting preferences of members of their networks, the information required on network members, and the treatment of endogeneity in the analysis.
A Multivariate Evaluation of 25 Proximal and Distal Risk-Factors for Gambling-Related Harm

Individual differences in the risk of developing gambling-related harm play an important role in theoretical models and practical interventions. The present study attempted comprehensive measurement and evaluation of 25 known risk factors for gambling-related harm in order to determine which factors provided large and unique explanatory power. We surveyed 1650 regular gamblers from an online panel, screening in 1174 (466 male) who passed all checks of attention and response consistency. We evaluated each risk factor based on bivariate correlations with harms, then made separate multivariate evaluations of proximal (e.g., gambling motivations) and distal (e.g., religiosity) risk factors. Almost all bivariate correlations were significant, but most distal factors were not significant in multivariate models. Trait impulsivity was the most important risk factor by a large margin. Excessive consumption, less use of safe gambling practices, and more fallacies were key proximal risks of harm. Many well-known correlates of gambling harm (e.g., youth, lower educational attainment) do not show a direct role in the development of gambling harm when controlling for other factors. The results support theoretical models that emphasise early conditioning and biological vulnerability (manifested through impulsivity). Since maladaptive cognitive and behavioural schemas appear to be more important than motivations (e.g., escape, excitement, ego), interventions may benefit by targeting these proximal drivers of harm.
Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway

Background Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved. Material/Methods Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3β-β/catenin pathway was detected by western blot. Results OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3β-β/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells. Conclusions OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3β-β/catenin pathway.
Cell Reprogramming in Tumorigenesis and Its Therapeutic Implications for Breast Cancer

Breast cancer is the most common malignancy in women worldwide and can be categorized into several subtypes according to histopathological parameters or genomic signatures. Such heterogeneity of breast cancer can arise from the reactivation of mammary stem cells in situ during tumorigenesis. Moreover, different breast cancer subtypes exhibit varieties of cancer incidence, therapeutic response, and patient prognosis, suggesting that a specific therapeutic protocol is required for each breast cancer subtype. Recent studies using molecular and cellular assays identified a link between specific genetic/epigenetic alterations and distinct cells of origin of breast cancer subtypes. These alterations include oncogenes, tumor suppressor genes, and cell-lineage determinants, which can induce cell reprogramming (dedifferentiation and transdifferentiation) among two lineage-committed mammary epithelial cells, namely basal and luminal cells. The interconversion of cell states through cell reprogramming into the intermediates of mammary stem cells can give rise to heterogeneous breast cancers that complicate effective therapies of breast cancer. A better understanding of mechanisms underlying cell reprogramming in breast cancer can help in not only elucidating tumorigenesis but also developing therapeutics for breast cancer. This review introduces recent findings on cancer gene-mediated cell reprogramming in breast cancer and discusses the therapeutic potential of targeting cell reprogramming.
Children’s Transport Built Environments: A Mixed Methods Study of Associations between Perceived and Objective Measures and Relationships with Parent Licence for Independent Mobility in Auckland, New Zealand

Children’s independent mobility is declining internationally. Parents are the gatekeepers of children’s independent mobility. This mixed methods study investigates whether parent perceptions of the neighbourhood environment align with objective measures of the neighbourhood built environment, and how perceived and objective measures relate to parental licence for children’s independent mobility. Parents participating in the Neighbourhood for Active Kids study (n = 940) answered an open-ended question about what would make their neighbourhoods better for their child’s independent mobility, and reported household and child demographics. Objective measures of the neighbourhood built environment were generated using geographic information systems. Content analysis was used to classify and group parent-reported changes required to improve their neigbourhood. Parent-reported needs were then compared with objective neighbourhood built environment measures. Linear mixed modelling examined associations between parental licence for independent mobility and (1) parent neighbourhood perceptions; and (2) objectively assessed neighbourhood built environment features. Parents identified the need for safer traffic environments. No significant differences in parent reported needs were found by objectively assessed characteristics. Differences in odds of reporting needs were observed for a range of socio-demographic characteristics. Parental licence for independent mobility was only associated with a need for safer places to cycle (positive) and objectively assessed cycling infrastructure (negative) in adjusted models. Overall, the study findings indicate the importance of safer traffic environments for children’s independent mobility.
Competitive Frontoparietal Interactions Mediate Implicit Inferences

Frequent experience with regularities in our environment allows us to use predictive information to guide our decision process. However, contingencies in our environment are not always explicitly present and sometimes need to be inferred. Heretofore, it remained unknown how predictive information guides decision-making when explicit knowledge is absent and how the brain shapes such implicit inferences. In the present experiment, 17 human participants (9 females) performed a discrimination task in which a target stimulus was preceded by a predictive cue. Critically, participants had no explicit knowledge that some of the cues signaled an upcoming target, allowing us to investigate how implicit inferences emerge and guide decision-making. Despite unawareness of the cue–target contingencies, participants were able to use implicit information to improve performance. Concurrent EEG recordings demonstrate that implicit inferences rely upon interactions between internally and externally oriented networks, whereby prefrontal regions inhibit parietal cortex under internal implicit control. SIGNIFICANCE STATEMENT Regularities in our environment can guide our behavior providing information about upcoming events. Interestingly, such predictive information does not need to be explicitly represented to effectively guide our decision process. Here, we show how the brain engages in such real-world “data mining” and how implicit inferences emerge. We used a contingency cueing task and demonstrated that implicit inferences influenced responses to subsequent targets despite a lack of awareness of cue–target contingencies. Further, we show that these implicit inferences emerge through interactions between internally and externally oriented neural networks. The current results highlight the importance of prefrontal processes in transforming external events into predictive internalized models of the world.
Severe thermoregulatory deficiencies in mice with a deletion in the titin gene TTN

ABSTRACT Muscular dystrophy with myositis (mdm) mice carry a deletion in the N2A region of the gene for the muscle protein titin (TTN), shiver at low frequency, fail to maintain body temperatures (Tb) at ambient temperatures (Ta) <34°C, and have reduced body mass and active muscle stiffness in vivo compared with wild-type (WT) siblings. Impaired shivering thermogenesis (ST) could be due to the mutated titin protein causing more compliant muscles. We hypothesized that non-shivering thermogenesis (NST) is impaired. To characterize the response to cold exposure, we measured Tb and metabolic rate (MR) of WT and mdm mice at four nominal temperatures: 20, 24, 29 and 34°C. Subsequently, we stimulated NST with noradrenaline. Manipulation of Ta revealed an interaction between genotype and MR: mdm mice had higher MRs at 29°C and lower MRs at 24°C compared with WT mice. NST capacity was lower in mdm mice than in WT mice. Using MR data from a previous study, we compared MR of mdm mice with MR of Perognathus longimembris, a mouse species of similar body mass. Our results indicated low MR and reduced NST of mdm mice. These were more pronounced than differences between mdm and WT mice owing to body mass effects on MR and capacity for NST. Correcting MR using Q10 showed that mdm mice had lower MRs than size-matched P. longimembris, indicating that mutated N2A titin causes severe thermoregulatory defects at all levels. Direct effects of the titin mutation lead to lower shivering frequency. Indirect effects likely lead to a lower capacity for NST and increased thermal conductance through decreased body size. Summary: Mice with a small deletion in the titin gene TTN exhibit severe thermoregulatory deficiencies and have lower metabolic rates than other size-matched rodents.
On the differences between mega‐ and meta‐imputation and analysis exemplified on the genetics of age‐related macular degeneration

While current genome‐wide association analyses often rely on meta‐analysis of study‐specific summary statistics, individual participant data (IPD) from multiple studies increase options for modeling. When multistudy IPD is available, however, it is unclear whether this data is to be imputed and modeled across all participants (mega‐imputation and mega‐analysis) or study‐specifically (meta‐imputation and meta‐analysis). Here, we investigated different approaches toward imputation and analysis using 52,189 subjects from 25 studies of the International Age‐related Macular Degeneration (AMD) Genomics Consortium including, 16,144 AMD cases and 17,832 controls for association analysis.
Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

Currently, there are no commercially available live‐attenuated vaccines against chikungunya virus (CHIKV). Here, CHIKVs with mutations in non‐structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type‐I IFN response compared to WT‐CHIKV. Adult mice infected with this nsP‐mutant exhibited a mild joint phenotype with low‐level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti‐inflammatory IL‐10 versus pro‐inflammatory IL‐1β and IL‐18 balance during CHIKV nsP‐mutant infection that modified acute antiviral and cell signaling canonical pathways. Challenging CHIKV nsP‐mutant‐infected mice with WT‐CHIKV or the closely related O'nyong‐nyong virus resulted in no detectable viremia, observable joint inflammation, or damage. Challenged mice showed high antibody titers with efficient neutralizing capacity, indicative of immunological memory. Manipulating molecular processes that govern CHIKV replication could lead to plausible vaccine candidates against alphavirus infection.
Parasites and Cancer - A Molecular Insight

Cancer due to parasitic infection is one of the important causes of cancer. Parasites have an oncogenic potential of causing tumor formation in humans. Trematode parasite species such as Schistosoma haematobium and liver flukes such as Opisthorchis viverrini , Clonorchis sinensis are the major cause of bladder cancer. p53 is most widely used genetic marker in the bladder cancer. Micro RNA’s that are differentially expressed in cancer cells, compared to that of normal cells could be used as marker for functional analysis of up regulation and down regulation of genes. Further research on functional characterization of Micro RNA’s could eventually lead to the development of Micro RNA based therapeutics.