Miracle-dz/UniFAR-FTUs huggingface dataset:
Compressive Force Spectroscopy: From Living Cells to Single Proteins

One of the most successful applications of atomic force microscopy (AFM) in biology involves monitoring the effect of force on single biological molecules, often referred to as force spectroscopy. Such studies generally entail the application of pulling forces of different magnitudes and velocities upon individual molecules to resolve individualistic unfolding/separation pathways and the quantification of the force-dependent rate constants. However, a less recognized variation of this method, the application of compressive force, actually pre-dates many of these “tensile” force spectroscopic studies. Further, beyond being limited to the study of single molecules, these compressive force spectroscopic investigations have spanned samples as large as living cells to smaller, multi-molecular complexes such as viruses down to single protein molecules. Correspondingly, these studies have enabled the detailed characterization of individual cell states, subtle differences between seemingly identical viral structures, as well as the quantification of rate constants of functionally important, structural transitions in single proteins. Here, we briefly review some of the recent achievements that have been obtained with compressive force spectroscopy using AFM and highlight exciting areas of its future development.
Understanding environmental contributions to autism: Causal concepts and the state of science

The complexity of neurodevelopment, the rapidity of early neurogenesis, and over 100 years of research identifying environmental influences on neurodevelopment serve as backdrop to understanding factors that influence risk and severity of autism spectrum disorder (ASD). This Keynote Lecture, delivered at the May 2016 annual meeting of the International Society for Autism Research, describes concepts of causation, outlines the trajectory of research on nongenetic factors beginning in the 1960s, and briefly reviews the current state of this science. Causal concepts are introduced, including root causes; pitfalls in interpreting time trends as clues to etiologic factors; susceptible time windows for exposure; and implications of a multi‐factorial model of ASD. An historical background presents early research into the origins of ASD. The epidemiologic literature from the last fifteen years is briefly but critically reviewed for potential roles of, for example, air pollution, pesticides, plastics, prenatal vitamins, lifestyle and family factors, and maternal obstetric and metabolic conditions during her pregnancy. Three examples from the case‐control CHildhood Autism Risks from Genes and the Environment Study are probed to illustrate methodological approaches to central challenges in observational studies: capturing environmental exposure; causal inference when a randomized controlled clinical trial is either unethical or infeasible; and the integration of genetic, epigenetic, and environmental influences on development. We conclude with reflections on future directions, including exposomics, new technologies, the microbiome, gene‐by‐environment interaction in the era of –omics, and epigenetics as the interface of those two. As the environment is malleable, this research advances the goal of a productive and fulfilling life for all children, teen‐agers and adults. Autism Res 2018, 11: 554–586. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
Nanoindentation characterisation of carbon fibre reinforced plastic microstructures

The increasing use of fibrous composite materials in the automotive and aerospace industries has led to increased demand for predictive analysis tools that require careful measurement of the fibre and matrix constituent properties in order to accurately predict the macroscopic deformation and failure response of the materials. Recent developments in nanoindentation testing have enabled accurate property measurements to be carried out at the scale required to probe the individual fibrous composite constituents in situ. However, quantitative characterisation of the matrix constituent has proven challenging due to the inhomogeneity of the composite microstructure and the non-linear time-dependent polymer matrix properties. Hence, a detailed experimental and numerical investigation was carried out into the use of nanoindentation to determine the in situ properties of the polymer matrix constituent in an aerospace grade carbon fibre reinforced epoxy composite (Hexcel HTA/6376). An experimental comparison of the bulk and in situ 6376 matrix properties was carried out using a state-of-the-art Nanoindenter G200, supplied by Agilent. The bulk matrix and composite material were co-cured to produce specimens ideal for matrix characterisation. It is found that the unconstrained in situ indentation modulus increased with a decrease in matrix pocket size, and was up to 19% greater than the bulk matrix modulus. However, a clear discrepancy was noted between the bulk matrix elastic modulus values derived from indentation testing and those determined using traditional macroscopic tensile tests, with the indentation modulus being consistently larger by approximately 40%. Thus, an investigation into the effects of pile-up, viscoelasticity and hydrostatic stress on the polymer indentation modulus was carried out and experimental and analytical techniques were developed to account for viscous and hydrostatic stress effects that systematically reduced the calculated modulus to within 3% of the macroscopic value. The proposed techniques move towards addressing the well-known disparity between nanoindentation and macroscopic measured moduli. Numerical studies using non-linear Finite Element Analysis were carried out to provide insight into the experimental observations and to help decouple highly interdependent variables, such as fibre constraint and residual stress effects on matrix properties. The apparent indentation modulus was found to increase by up to 47% due to the added constraint of the surrounding discrete fibre regions. A two-step modelling approach was used to determine the effect of residual stress states in two regions of interest, namely, the pocket and interfacial matrix regions following thermal cool-down of the composite from cure temperature. It is found that the hardness property decreased for the majority of the residual stress states, whereas the modulus property was found to be insensitive to residual stress.
Altered Brain Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Patients: A Resting-State fMRI Study

Type 2 diabetes mellitus (T2DM) affects a vast population and is closely associated with cognitive impairment. However, the mechanisms of cognitive impairment in T2DM patients have not been unraveled. Research on the basic units (nodes or hubs and edges) of the brain functional network on the basis of neuroimaging may advance our understanding of the network change pattern in T2DM patients. This study investigated the change patterns of brain functional hubs using degree centrality (DC) analysis and the connectivity among these hubs using functional connectivity and Granger causality analysis. Compared to healthy controls, the DC values were higher in the left anterior cingulate gyrus (ACG) and lower in the bilateral lateral occipital cortices (LOC) and right precentral gyrus (PreCG) in T2DM patients. The functional connectivity between the left ACG and the right PreCG was stronger in T2DM patients, whereas the functional connectivity among the right PreCG and bilateral LOC was weaker. A negative causal effect from the left ACG to left LOC and a positive effect from the left ACG to right LOC were observed in T2DM patients, while in healthy controls, the opposite occurred. Additionally, the reserve of normal brain function in T2DM patients was negatively associated with the elevated glycemic parameters. This study demonstrates that there are brain functional hubs and connectivity alterations that may reflect the aberrant information communication in the brain of T2DM patients. The findings may advance our understanding of the mechanisms of T2DM-related cognitive impairment.
Assessing the Risk of Drug-Induced Cholestasis Using Unbound Intrahepatic Concentrations

Inhibition of the bile salt export pump (BSEP) has been recognized as a key factor in the development of drug-induced cholestasis (DIC). The risk of DIC in humans has been previously assessed using in vitro BSEP inhibition data (IC50) and unbound systemic drug exposure under assumption of the “free drug hypothesis. ” This concept, however, is unlikely valid, as unbound intrahepatic drug concentrations are affected by active transport and metabolism. To investigate this hypothesis, we experimentally determined the in vitro liver-to-blood partition coefficients (Kpuu) for 18 drug compounds using the hepatic extended clearance model (ECM). In vitro–in vivo translatability of Kpuu values was verified for a subset of compounds in rat. Consequently, unbound intrahepatic concentrations were calculated from clinical exposure (systemic and hepatic inlet) and measured Kpuu data. Using these values, corresponding safety margins against BSEP IC50 values were determined and compared with the clinical incidence of DIC. Depending on the ECM class of a drug, in vitro Kpuu values deviated up to 14-fold from unity, and unbound intrahepatic concentrations were affected accordingly. The use of in vitro Kpuu-based safety margins allowed separation of clinical cholestasis frequency into three classes (no cholestasis, cholestasis in ≤2%, and cholestasis in >2% of subjects) for 17 out of 18 compounds. This assessment was significantly superior compared with using unbound extracellular concentrations as a surrogate for intrahepatic concentrations. Furthermore, the assessment of Kpuu according to ECM provides useful guidance for the quantitative evaluation of genetic and physiologic risk factors for the development of cholestasis.
Assessment of physical activity intensity and duration in the paediatric population: evidence to support an a priori hypothesis and sample size in the agreement between subjective and objective methods

We aimed to provide evidence for an a priori hypothesis and sample size for subjectively assessing physical activity intensity and duration in paediatric population, adopting objective methods as the reference. We searched electronic databases, reference lists and author databases. Correlation coefficients were pooled as an indicator of agreement estimates. We found 183 agreement analyses (94.5% based on correlation coefficients) from 89 studies that met our inclusion criteria. We identified four physical activity parameters addressing intensity and two parameters addressing duration. The physical activity parameters focusing on intensity were measured only by questionnaires, and the best correlation was achieved by moderate‐to‐vigorous physical activity compared with a heart rate monitor. In addition, total physical activity duration had a stronger correlation with an accelerometer when measured by diaries or logs than when measured by questionnaires. In both cases, the correlation was moderate. Studies with sample sizes between 50 and 99 subjects showed measurements that were stable in both magnitude and interpretation. Our findings suggest that the agreement between subjective and objective methods for assessing physical activity intensity and duration is weak to moderate. Furthermore, sample sizes ranging from 50 to 99 subjects provide stable agreement estimates between methods.
Hot Isostatic Pressing of Transparent Nd:YAG Ceramics

This paper demonstrates that fine-grained (2–3 μm), transparent Nd:YAG can be achieved at SiO2 doping levels as low as 0.02 wt% by the sinter plus hot isostatic pressing (HIP) approach. Fine grain size is assured by sintering to 98% density, in order to limit grain growth, followed by HIP. Unlike dry-pressed samples, tape-cast samples were free of large, agglomerate-related pores after sintering, and thus high transparency (i.e., >80% transmission at 1064 nm) could be achieved by HIP at <1750°C along with lower silica levels, thereby avoiding conditions shown to cause exaggerated grain growth. Grain growth was substantially limited at lower SiO2 levels because silica is soluble in the YAG lattice up to ∼0.02–0.1 wt% at 1750°C, thus allowing sintering and grain growth to occur by solid-state diffusional processes. In contrast, liquid phase enhanced densification and grain growth occur at ∼0.08–0.14 wt% SiO2, especially at higher temperatures, because the SiO2 solubility limit is exceeded.
Effects of landuse intensification on stream basal resources and invertebrate communities

Human population growth and development have degraded freshwater ecosystems through direct negative effects on basal resources and higher trophic levels. Knowledge of how basal resources are influenced by anthropogenic activities is needed to examine foodweb responses and to evaluate negative effects of human disturbance. We combined quantitative sampling of all putative resources and consumers and naturally occurring stable isotopes of resource C and N to investigate how land use influences characteristics of basal resources (leaf litter, fine particulate organic matter [FPOM] suspended in water, FPOM deposited in pools, and epilithon) and the invertebrate communities in 9 streams of British Columbia (Canada) on a seasonal basis. Study streams were grouped as forest, cropland, and urban, based on percentages of land use in their catchments. We tested for seasonal and spatial differences in biomass, isotopic variability, and overlap of different basal resources and their relationships with invertebrate communities. Our results show that landuse intensification promotes wholesale degradation, which includes deterioration of water quality, changes to the quantity and quality of basal resources, and shifts in community structure of benthic invertebrates. Stream basal resources showed large variations in isotopic signatures caused by landuse changes, with the largest isotopic variability observed in cropland streams and the smallest in urban streams. Invertebrate communities had fewer taxa and reduced functional diversity in impaired streams (i.e., cropland and urban) via simplification of feeding styles of consumers, probably because of bottom-up controls. Our study highlights the importance of quantifying the isotopic variability of basal resources to estimate effects on food webs over time and along landuse intensification gradients.
The impact of global warming on germination and seedling emergence in Alliaria petiolata, a woodland species with dormancy loss dependent on low temperature.

The impact of global warming on seed dormancy loss and germination was investigated in Alliaria petiolata (garlic mustard), a common woodland/hedgerow plant in Eurasia, considered invasive in North America. Increased temperature may have serious implications, since seeds of this species germinate and emerge at low temperatures early in spring to establish and grow before canopy development of competing species. Dormancy was evaluated in seeds buried in field soils. Seedling emergence was also investigated in the field, and in a thermogradient tunnel under global warming scenarios representing predicted UK air temperatures through to 2080. Dormancy was simple, and its relief required the accumulation of low temperature chilling time. Under a global warming scenario, dormancy relief and seedling emergence declined and seed mortality increased as soil temperature increased along a thermal gradient. Seedling emergence advanced with soil temperature, peaking 8 days earlier under 2080 conditions. The results indicate that as mean temperature increases due to global warming, the chilling requirement for dormancy relief may not be fully satisfied, but seedling emergence will continue from low dormancy seeds in the population. Adaptation resulting from selection of this low dormancy proportion is likely to reduce the overall population chilling requirement. Seedling emergence is also likely to keep pace with the advancement of biological spring, enabling A. petiolata to maintain its strategy of establishment before the woodland canopy closes. However, this potential for adaptation may be countered by increased seed mortality in the seed bank as soils warm.
Impact of methionine oxidation as an initial event on the pathway of human prion protein conversion

Prion diseases comprise a group of fatal neurodegenerative disorders characterized by the autocatalytic conversion of the cellular prion protein PrPC into the infectious misfolded isoform PrPSc. Increasing evidence supports a specific role of oxidative stress in the onset of pathogenesis. Although the associated molecular mechanisms remain to be elucidated in detail, several studies currently suggest that methionine oxidation already detected in misfolded PrPSc destabilizes the native PrP fold as an early event in the conversion pathway. To obtain more insights about the specific impact of surface-exposed methionine residues on the oxidative-induced conversion of human PrP we designed, produced, and comparatively investigated two new pseudosulfoxidation mutants of human PrP 121–231 that comprises the well-folded C-terminal domain. Applying circular dichroism spectroscopy and dynamic light scattering techniques we showed that pseudosulfoxidation of all surface exposed Met residues formed a monomeric molten globule-like species with striking similarities to misfolding intermediates recently reported by other groups. However, individual pseudosulfoxidation at the polymorphic M129 site did not significantly contribute to the structural destabilization. Further metal-induced oxidation of the partly unfolded pseudosulfoxidation mutant resulted in the formation of an oligomeric state that shares a comparable size and stability with PrP oligomers detected after the application of different other triggers for structural conversion, indicating a generic misfolding pathway of PrP. The obtained results highlight the specific importance of methionine oxidation at surface exposed residues for PrP misfolding, strongly supporting the hypothesis that increased oxidative stress could be one causative event for sporadic prion diseases and other neurodegenerative disorders.
In situ characterization of soil properties using visible near-infrared diffuse reflectance spectroscopy

In Situ Characterization of Soil Properties Using Visible Near-Infrared Diffuse Reflectance Spectroscopy. (May 2006) Travis Heath Waiser, B.S., Texas A&M University Chair of Advisory Committee: Dr. Cristine Morgan Diffuse reflectance spectroscopy (DRS) is a rapid proximal-sensing method that is being used more and more in laboratory settings to measure soil properties. Diffuse reflectance spectroscopy research that has been completed in laboratories shows promising results, but very little has been reported on how DRS will work in a field setting on soils scanned in situ. Seventy-two soil cores were obtained from six fields in Erath and Comanche County, Texas. Each soil core was scanned with a visible nearinfrared (VNIR) spectrometer with a spectral range of 350-2500 nm in four different combinations of moisture content and pre-treatment: field-moist in situ, air-dried in situ, field-moist smeared in situ, and air-dried ground. Water potential was measured for the field-moist in situ scans. The VNIR spectra were used to predict total and fine clay content, water potential, organic C, and inorganic C of the soil using partial least squares (PLS) regression. The PLS model was validated with data 30% of the original soil cores that were randomly selected and not used in the calibration model. The root mean squared deviation (RMSD) of the air-dry ground samples were within the in situ RMSD and comparable to literature values for each soil property. The validation data set had a total clay content root mean squared deviation (RMSD) of 61 g kg and 41 g kg for the
Food service practices in Indian hotel organisations: an investigation of F&B managers' perceptions.

2 Abstract: The study is developed to explore the extent of inclusion of food service practices in the product offer by Indian hotel industry and to find if these services depend on the organisational demographic characteristics. The study was limited to the hotels that provide sleeping accommodations and meal options in India. The respondents were 200 food and beverage managers of these businesses. The findings show that the hotels are mostly sole proprietorship and most managers are college graduates and male. A structured instrument was developed to examine the food service practices. Based on a survey of 200 food and beverage manager's perceptions on food service practices were assessed by a 19- food service practices and 5 demographic characteristics. Factor analysis was performed to identify service practices, one-way ANOVA was employed to test the association of the demographic characteristics with food service practices. Results indicated that serving the guest within the estimated time given to the guest makes a guest delight', 'the way the food is presented and served in the tray to the guest creates an impact on the guest mind', 'quality holds more importance than quantity', 'training of employees should be carried out for serving complicated dishes' and ' suggesting a complimentary dish if a guest is not satisfied with the service offered by you is a good idea, may constitute the most important food service practices in the Indian hotels. Further, the results revealed that there is a positive relationship between food service practice variables and category and type of sample hotels, but there is no relationship between food service practices variables and age, number of employee and size of capital. The study makes a modest attempt to add information to the very little empirical knowledge available referring to the food service practices in Indian hotel industry.
Comparative Study of Microwave Assisted Hydro-Distillation with Conventional Hydro-Distillation for Extraction of Essential Oil from Piper betle L

Microwave assisted hydro-distillation (MAHD) is a new technique utilizing a modified microwave oven with Clevenger apparatus in the extraction process. MAHD was carried out to study its effect on extraction process at different power levels and leaf to water ratio. The MAHD extraction method was compared with conventional hydrodistillation (CHD) for extraction of essential oil (EO) from betel leaf (Piper betle L.) in terms of extraction yield, extraction time, energy requirement and quality of essential oil obtained. The extraction yield was generally improved by increasing microwave power level and also by increasing leaf to water ratio. The main components found by gas chromatography mass spectrometry (GC-MS) analysis were same for the oil extracted from both MAHD and CHD. There is no significant difference in the results obtained from physical properties and radical scavenging activity evaluation. MAHD was found to be more energy efficient and required less extraction time (50 minutes as compared to 210 minutes in CHD) without adversely affecting the quality of essential oil. The results obtained in this study encouraged the application of MAHD method for extraction of the essential oil. Therefore, it can be used as a good alternative method to obtain essential oils from betel leaf.