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The pregnancy period represents a unique window of opportunity to identify risks to both the fetus and mother and to deter the intergenerational transmission of adversity and mental health problems. Although the maternal–fetal dyad is especially vulnerable to the effects of stress during pregnancy, less is known about how the dyad is also receptive to salutary, resilience-promoting influences. The present review adopts life span and intergenerational perspectives to review four key areas of research. The first part describes how pregnancy is a sensitive period for both the mother and fetus. In the second part, the focus is on antecedents of maternal prenatal risks pertaining to prenatal stress response systems and mental health. The third part then turns to elucidating how these alterations in prenatal stress physiology and mental health problems may affect infant and child outcomes. The fourth part underscores how pregnancy is also a time of heightened fetal receptivity to maternal and environmental signals, with profound implications for adaptation. This section also reviews empirical evidence of promotive and protective factors that buffer the mother and fetus from developmental and adaptational problems and covers a sample of rigorous evidence-based prenatal interventions that prevent maladaptation in the maternal–fetal dyad before babies are born. Finally, recommendations elaborate on how to further strengthen understanding of pregnancy as a period of multilevel risk and resilience, enhance comprehensive prenatal screening, and expand on prenatal interventions to promote maternal–fetal adaptation before birth.

Earthquake engineers continually face challenges in how to implement ridge/hill amplification to transfer predicted peak horizontal acceleration (PHA) near the base using a ground motion prediction equation (GMPE) to the desired location on the ridge to compute the design forces. There are very few relations available for the prediction of 2D ridge amplification only, irrespective of geometry. This paper presents the development of relationships for the prediction of ridge amplification based on the numerically simulated seismic responses of the 2D triangular and elliptical and 3D conical and ellipsoidal ridge models for different shape ratios. The variation in ridge effects with the change of azimuth of a site on a hill is also considered in the development of relationships. The analysis of simulated results revealed very large amplitude and spectral amplifications as well as average spectral amplifications (ASA) in the case of 3D ridges as compared to the corresponding 2D ridges. An increase in ridge amplification with an increase in shape ratio is observed for both the 2D and 3D ridge models. An increase in the fundamental frequency of ridges with an increase in shape ratio is observed for a particular width. The analysis of snapshots of the seismic wave field reveals the need for computation of amplitude amplification and associated strain within the hill mass for a tunnel design. It is concluded that the estimated ridge amplification using earthquake records and standard spectral ratio method gives an overestimate due to the de-amplification at the reference station as well as a false fundamental frequency. The developed relations for the 2D and 3D ridges predict amplitude amplification as well as ASA for a particular value of normalised elevation and shape ratio. These relations can be conservatively used by the field earthquake engineer to predict the PHA at any location on a hill (taking into account the dimensionality and shape of the real hill mass), if the same is available at the base of that hill mass using a GMPE.

This paper presents the physics based ground motion synthetics and its earthquake engineering consequences in the National Capital Territory (NCT) Delhi, India due to the Mw8.2 scenario earthquake on the Nahan segment of the western Himalaya. In order to fulfill the aim, a state-of-the-art pseudo-dynamic rupture is implemented in a 3D fourth-order staggered-grid viscoelastic time-domain finite-difference code. The ground motion is simulated in a frequency bandwidth of 0–2.5 Hz at the basement level at 158 locations of the NCT Delhi. The computed transverse component of velocity time series at the basement level is numerically transferred to the free surface taking into account the rheological parameters of the sediment deposit. Upon first inspection, the estimated range of peak ground acceleration, between 0.017–0.12 g, indicates that all the buildings in the NCT Delhi will remain safe in the event of an Mw8.2 Nahan earthquake, provided they are constructed in accordance with Indian building codes. But, the computed acceleration response spectra (Sa) depicts that some of the high-rise buildings of the NCT Delhi may suffer minor damage to collapse under partial or complete double resonance condition due to Sa exceeding the DBE and MCE levels. The obtained range of pseudo-spectral displacements (Sd) reveals the need of performance-based design for high-rise buildings in the NCT Delhi, so that they can withstand under partial or complete double resonance condition during the occurrence of Nahan earthquakes. The developed contour maps of Sa and Sd at different periods can be used for the retrofitting and forced-based and displacement-based designs of the high-rise buildings.

KEY MESSAGE : EaDREB2 overexpressed in sugarcane enhanced tolerance to drought and salinity. When co-transformed with plant DNA helicase gene, DREB2 showed greater level of salinity tolerance than in single-gene transgenics. Drought is one of the most challenging agricultural issues limiting sustainable sugarcane production and can potentially cause up to 50 % yield loss. DREB proteins play a vital regulatory role in abiotic stress tolerance in plants. We previously reported that expression of EaDREB2 is enhanced by drought stress in Erianthus arundinaceus. In this study, we have isolated the DREB2 gene from E. arundinaceus, transformed one of the most popular sugarcane variety Co 86032 in tropical India with EaDREB2 through Agrobacterium-mediated transformation, pyramided the EaDREB2 gene with the gene coding for PDH45 driven by Port Ubi 2.3 promoter through particle bombardment and evaluated the V₁transgenics for soil deficit moisture and salinity stresses. Soil moisture stress was imposed at the tillering phase by withholding irrigation. Physiological, molecular and morphological parameters were used to assess drought tolerance. Salinity tolerance was assessed through leaf disc senescence and bud sprout assays under salinity stress. Our results indicate that overexpression of EaDREB2 in sugarcane enhances drought and salinity tolerance to a greater extent than the untransformed control plants. This is the first report of the co-transformation of EaDREB2 and PDH45 which shows higher salinity tolerance but lower drought tolerance than EaDREB2 alone. The present study seems to suggest that, for combining drought and salinity tolerance together, co-transformation is a better approach.

This paper presents the quantification of the role of structural parameters and impedance contrast in the insulation and meta-capacity of a city for Rayleigh waves at an earthquake engineering scale. The feasibility of developing heterogeneous and homogeneous meta-cities in a soft sediment deposit is investigated using the meta-behavior of structures and meta-blocks in the epicentral zone of shallow crustal earthquakes. The Rayleigh wave and horizontally propagating plane SH-wave responses of the city with different structural parameters and impedance contrast are simulated at the top of the structure as well as at the free field after crossing the city. It is concluded that the structures act as a meta-structure for the Rayleigh waves but not for the Love waves, and the meta-capacity of the city increases with the increase in the number and stiffness of structures and decrease in damping and impedance contrast. An increase in the width of bandgaps at different longitudinal modes of vibration of structures is obtained with a decrease in impedance contrast, particularly when it is less than 15. It is concluded that meta-blocks can be developed using appropriate ceramic material considering the half-space impedance to develop a desired bandgap for Rayleigh waves. Based on the obtained increase in the city’s insulation capacity for Rayleigh waves with the increase in the number and width of structures and decrease in impedance contrast, it is recommended that engineers consider the urban layer as lying in the path of Rayleigh waves for the estimation of seismic hazard in the epicentral zone of shallow crustal earthquakes.

In this manuscript, recent advancements in the area of minimally-invasive transdermal biosensing and drug delivery are reviewed. The administration of therapeutic entities through the skin is complicated by the stratum corneum layer, which serves as a barrier to entry and retards bioavailability. A variety of strategies have been adopted for the enhancement of transdermal permeation for drug delivery and biosensing of various substances. Physical techniques such as iontophoresis, reverse iontophoresis, electroporation, and microneedles offer (a) electrical amplification for transdermal sensing of biomolecules and (b) transport of amphiphilic drug molecules to the targeted site in a minimally invasive manner. Iontophoretic delivery involves the application of low currents to the skin as well as the migration of polarized and neutral molecules across it. Transdermal biosensing via microneedles has emerged as a novel approach to replace hypodermic needles. In addition, microneedles have facilitated minimally invasive detection of analytes in body fluids. This review considers recent innovations in the structure and performance of transdermal systems.

Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly resected patient tumors as a proof of concept for this approach. Hepatoblastoma tumor organoids recapitulate the key elements of patient tumors, including tumor architecture, mutational profile, gene expression patterns, and features of Wnt/β-catenin signaling that are hallmarks of hepatoblastoma pathophysiology. Tumor organoids were successfully used alongside non-tumor liver organoids from the same patient to perform a drug screen using twelve candidate compounds. One drug, JQ1, demonstrated increased destruction of liver organoids from hepatoblastoma tumor tissue relative to organoids from the adjacent non-tumor liver. Our findings suggest that hepatoblastoma organoids could be used for a variety of applications and have the potential to improve treatment options for the subset of hepatoblastoma patients who do not respond to existing treatments.

Heart failure resulting from acute myocardial infarction (AMI) is an important global health problem. Treatments of heart failure and AMI have improved significantly over the past two decades; however, the available diagnostic tests only give limited insights into these heterogeneous conditions at a reversible stage and are not precise enough to evaluate the status of the tissue at high risk. Innovative diagnostic tools for more accurate, more reliable, and early diagnosis of AMI are urgently needed. A promising solution is the timely identification of prognostic biomarkers, which is crucial for patients with AMI, as myocardial dysfunction and infarction lead to more severe and irreversible changes in the cardiovascular system over time. The currently available biomarkers for AMI detection include cardiac troponin I (cTnI), cardiac troponin T (cTnT), myoglobin, lactate dehydrogenase, C-reactive protein, and creatine kinase and myoglobin. Most recently, electrochemical biosensing technologies coupled with graphene quantum dots (GQDs) have emerged as a promising platform for the identification of troponin and myoglobin. The results suggest that GQDs-integrated electrochemical biosensors can provide useful prognostic information about AMI at an early, reversible, and potentially curable stage. GQDs offer several advantages over other nanomaterials that are used for the electrochemical detection of AMI such as strong interactions between cTnI and GQDs, low biomarker consumption, and reusability of the electrode; graphene-modified electrodes demonstrate excellent electrochemical responses due to the conductive nature of graphene and other features of GQDs (e.g., high specific surface area, π–π interactions with the analyte, facile electron-transfer mechanisms, size-dependent optical features, interplay between bandgap and photoluminescence, electrochemical luminescence emission capability, biocompatibility, and ease of functionalization). Other advantages include the presence of functional groups such as hydroxyl, carboxyl, carbonyl, and epoxide groups, which enhance the solubility and dispersibility of GQDs in a wide variety of solvents and biological media. In this perspective article, we consider the emerging knowledge regarding the early detection of AMI using GQDs-based electrochemical sensors and address the potential role of this sensing technology which might lead to more efficient care of patients with AMI.

This article systematically overviews the grain size effect on deformation twinning and detwinning in face-centered cubic (fcc) metals. With decreasing grain size, coarse-grained fcc metals become more difficult to deform by twinning, whereas nanocrystalline (nc) fcc metals first become easier to deform by twinning and then become more difficult, exhibiting an optimum grain size for twinning. The transition in twinning behavior from coarse-grained to nc fcc metals is caused by the change in deformation mechanisms. An analytical model based on observed deformation physics in nc metals, i.e., grain boundary emission of dislocations, provides an explanation of the observed optimum grain size for twinning in nc fcc metals. The detwinning process is caused by the interaction between dislocations and twin boundaries. Under a certain deformation condition, there exists a grain size range where the twinning process dominates over the detwinning process to produce the highest density of twins.