Search

Natural and man-made disasters pose a threat to human life, flora-fauna, and infrastructure. It is critical to detect the damage quickly and accurately for infrastructures right after the occurrence of any disaster. The detection and assessment of infrastructure damage help manage financial strategy as well. Recently, many researchers and agencies have made efforts to create high-resolution satellite imageries database related to pre and post-disaster events. The advanced remote sensing satellite imageries can reflect the surface of the earth accurately up to 30 cm spatial resolution on a daily basis. These high spatial resolutions (HSR) imageries can help access any natural hazard's damage by comparing the pre- and post-disaster data. These remote sensing imageries have limitations, such as cloud occlusions. Building under a thick cloud cannot be recognised in optical images. The manual assessment of the severity of damage to buildings/infrastructure by comparing bi-temporal HSR imageries or airborne will be a tedious and subjective job. On the other hand, the emerging use of unmanned aired vehicles (UAV) can be used to assess the situation precisely. The high-resolution UAV imageries and the HSR satellite imageries can complement each other for critical infrastructure damage assessment. In this study, a novel approach is used to integrate UAV data into HSR satellite imageries for the building damage assessment using a convolution neural network (CNN) based deep learning model. The research work is divided into two fundamental sub-tasks: first is the building localisation in the pre-event images, and second is the damage classification by assigning a unique damage level label reflecting the degree of damage to each building instance on the post-disaster images. For the study, the HSR satellite imageries of 36 pairs of pre- and post natural hazard events is acquired for the year 2021-22, similarly available UAV based data for these events is also collected from the open data source. The data is then pre-processed, and the building damage is assessed using a deep object-based semantic change detection framework (ChangeOS). The mentioned model was trained on the xview2 building damage assessment datasets comprised of ~20,000 images with ~730,000 building polygons of pre and post disaster events over the globe from 2011-2018. The experimental setup in this study includes training on the global dataset and testing on the regional-scale building damage assessment using HSR satellite imageries and local-scale using UAV imageries. The result obtained from the bi-temporal assessment of HSR images for the Indonesia Earthquake 2022 has shown an F1 score of ~67%, while the Uttarakhand flooding event 2021 has reported an F1 score of ~64%. The HSR imageries from the UAV Haiti earthquake event in 2011 have also shown less but promising F1 scores of ~54%. It is inferred that merging HSR imageries from satellite and UAV for building damage assessment using the ChangeOS framework represents a robust tool to further promote future research in infrastructure maintenance strategy and policy management in disaster response.

Preclinical studies have shown that mesenchymal stem cells have a positive effect in perinatal brain injury models. The mechanisms that cause these neurotherapeutic effects are not entirely intelligible. Mitochondrial damage, inflammation, and reactive oxygen species are considered to be critically involved in the development of injury. Mesenchymal stem cells have immunomodulatory action and exert mitoprotective effects which attenuate production of reactive oxygen species and promote restoration of tissue function and metabolism after perinatal insults. This review summarizes the present state, the underlying causes, challenges and possibilities for effective clinical translation of mesenchymal stem cell therapy., Mesenchymal stem cells have a positive effect in perinatal brain injury models. Mitochondrial damage, inflammation, and reactive oxygen species are critically involved in the development of injury. Mesenchymal stem cells have immunomodulatory action and exert mitoprotective effects which attenuate production of reactive oxygen species and promote restoration of tissue function and metabolism after perinatal insults. This review summarizes the present state, the underlying causes, challenges and possibilities for effective clinical translation of mesenchymal stem cell therapy. The image illustrates transfer of mitochondria from mesenchymal stem cells to damaged neurons and inflamed microglia via tunneling nanotubes.

Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-alpha (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-alpha. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, I kappa B-alpha, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-alpha induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-alpha-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-alpha-induced microglia response for cytokines, chemokines, and phosphorylation of I kappa B-alpha. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge.

Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 Wistar rats were exposed to unilateral GMH through intracranial injection into the striatum close to the germinal matrix with 0.1, 0.2, or 0.3 U of collagenase VII. During 10 days following GMH induction, motor functions and body weight were assessed and brain tissue collected at P16. Animals were tested for anxiety, motor coordination and motor asymmetry on P22–26 and P36–40. Using immunohistochemical staining and neuropathological scoring we found that a collagenase dose of 0.3 U induced GMH. Neuropathological assessment revealed that the brain injury in the collagenase group was characterized by dilation of the ipsilateral ventricle combined with mild to severe cellular necrosis as well as mild to moderate atrophy at the levels of striatum and subcortical white matter, and to a lesser extent, hippocampus and cortex. Within 0.5 h post-collagenase injection there was clear bleeding at the site of injury, with progressive increase in iron and infiltration of neutrophils in the first 24 h, together with focal microglia activation. By P16, blood was no longer observed, although significant gray and white matter brain infarction persisted. Astrogliosis was also detected at this time-point. Animals exposed to GMH performed worse than controls in the negative geotaxis test and also opened their eyes with latency compared to control animals. At P40, GMH rats spent more time in the center of open field box and moved at higher speed compared to the controls, and continued to show ipsilateral injury in striatum and subcortical white matter. We have established a P5 rat model of collagenase-induced GMH for the study of preterm brain injury. Our results show that P5 rat pups exposed to GMH develop moderate brain injury affecting both gray and white matter associated with delayed eye opening and abnormal motor functions. These animals develop hyperactivity and show reduced anxiety in the juvenile stage.

Long-term performance of pavement sections depends on the structural integrity and strength of its individual layers. Clay-rich soils do not often meet the structural requirements needed to...

Durability is a major concern for all stabilised materials as it can reduce the structural capacity of pavement layers. One of the primary factors influencing the long-term performance of stabilise...

The emergence of Unmanned Aerial Vehicle (UAV) is driving a paradigm shift in research and development. Initially, UAVs were limited for defense purposes only. Now, these are getting popular and are widely used in different sectors such as infrastructure, mining, and media. With the increase in usage of UAVs, legal and policy complexities of drone laws have also increased. However, the current legal framework that regulates UAVs, needs to be reviewed due to the rapid increase in UAV’s market in India. The introduction of national drone policy from Director General of Civil Aviation (DGCA) which is UAVs regulatory body in India, reduces the ambiguities in the system. However, some bottlenecks still exist. The present policy legalizes the use and operation of drones in India which needs to be analyzed carefully. This paper examines the existing UAVs regulations and issues like safety, security, and privacy associated with the use of drones. The complexities in the existing law and major policy gaps in India are also analyzed. Moreover, a comparative analysis of existing national and international drone laws is presented with emphasis on the registration of aircraft and important guidelines in regard to the qualification and license for pilots.

Accumulating evidence suggests that changes in the metabolic signature of microglia underlie their response to inflammation. We sought to increase our knowledge of how pro-inflammatory stimuli induce metabolic changes. Primary microglia exposed to lipopolysaccharide (LPS)-expressed excessive fission leading to more fragmented mitochondria than tubular mitochondria. LPS-mediated Toll-like receptor 4 (TLR4) activation also resulted in metabolic reprogramming from oxidative phosphorylation to glycolysis. Blockade of mitochondrial fission by Mdivi-1, a putative mitochondrial division inhibitor led to the reversal of the metabolic shift. Mdivi-1 treatment also normalized the changes caused by LPS exposure, namely an increase in mitochondrial reactive oxygen species production and mitochondrial membrane potential as well as accumulation of key metabolic intermediate of TCA cycle succinate. Moreover, Mdivi-1 treatment substantially reduced LPS induced cytokine and chemokine production. Finally, we showed that Mdivi-1 treatment attenuated expression of genes related to cytotoxic, repair, and immunomodulatory microglia phenotypes in an in vivo neuroinflammation paradigm. Collectively, our data show that the activation of microglia to a classically pro-inflammatory state is associated with a switch to glycolysis that is mediated by mitochondrial fission, a process which may be a pharmacological target for immunomodulation.

Significance: Perinatal brain injury is caused by hypoxia–ischemia (HI) in term neonates, perinatal arterial stroke, and infection/inflammation leading to devastating long-term neurodevelopmental deficits. Therapeutic hypothermia is the only currently available treatment but is not successful in more than 50% of term neonates suffering from hypoxic–ischemic encephalopathy. Thus, there is an urgent unmet need for alternative or adjunct therapies. Reactive oxygen species (ROS) are important for physiological signaling, however, their overproduction/accumulation from mitochondria and endoplasmic reticulum (ER) during HI aggravate cell death. Recent Advances and Critical Issues: Mechanisms underlying ER stress-associated ROS production have been primarily elucidated using either non-neuronal cells or adult neurodegenerative experimental models. Findings from mature brain cannot be simply transferred to the immature brain. Therefore, age-specific studies investigating ER stress modulators may help investigate ER stress-associated ROS pathways in the immature brain. New therapeutics such as mitochondrial site-specific ROS inhibitors that selectively inhibit superoxide (O(2)(•−))/hydrogen peroxide (H(2)O(2)) production are currently being developed. Future Directions: Because ER stress and oxidative stress accentuate each other, a combinatorial therapy utilizing both antioxidants and ER stress inhibitors may prove to be more protective against perinatal brain injury. Moreover, multiple relevant targets need to be identified for targeting ROS before they are formed. The role of organelle-specific ROS in brain repair needs investigation. Antioxid. Redox Signal. 31, 643–663.

Infection and inflammation are known risk factors for neonatal brain injury. Mycoplasma and Gram-positive bacteria, for which Toll-like receptor 2 (TLR2) plays a key role in recognition and inflammatory response, are among the most common pathogens in the perinatal period. Here, we report that systemic activation of TLR2 by Pam3CSK4 (P3C) increases neural tissue loss and demyelination induced by subsequent hypoxia–ischemia (HI) in neonatal mice. High-resolution respirometry of brain isolated mitochondria revealed that P3C suppresses ADP-induced oxidative phosphorylation, the main pathway of cellular energy production. The results suggest that infection and inflammation might contribute to HI-induced energy failure.

Myocardial dysfunction is commonly associated with accumulation of cardiac lipid droplets (LDs). Perilipin 2 (Plin2) is a LD protein that is involved in LD formation, stability and trafficking events within the cell. Even though Plin2 is highly expressed in the heart, little is known about its role in myocardial lipid storage. A recent report shows that cardiac overexpression of Plin2 result in massive myocardial steatosis suggesting that Plin2 stabilizes LDs. In this study, we hypothesized that deficiency in Plin2 would result in reduced myocardial lipid storage. In contrast to our hypothesis, we found increased accumulation of triglycerides in hearts, and specifically in cardiomyocytes, from Plin2 −/− mice. Although Plin2 −/− mice had markedly enhanced lipid levels in the heart, they had normal heart function under baseline conditions and under mild stress. However, after an induced myocardial infarction, stroke volume and cardiac output were reduced in Plin2 −/− mice compared with Plin2 +/+ mice. We further demonstrated that the increased triglyceride accumulation in Plin2-deficient hearts was caused by altered lipophagy. Together, our data show that Plin2 is important for proper hydrolysis of LDs.

Magnesium sulphate (MgSO4) given to women in preterm labor reduces cerebral palsy in their offspring but the mechanism behind this protection is unclear, limiting its effective, safe clinical implementation. Previous studies suggest that MgSO4is not neuroprotective if administered during or after the insult, so we hypothesised that MgSO4induces preconditioning in the immature brain. Therefore, we administered MgSO4at various time-points before/after unilateral hypoxia-ischemia (HI) in seven-day-old rats. We found that MgSO4treatment administered as a bolus between 6 days and 12 h prior to HI markedly reduced the brain injury, with maximal protection achieved by 1.1 mg/g MgSO4administered 24 h before HI. As serum magnesium levels returned to baseline before the induction of HI, we ascribed this reduction in brain injury to preconditioning. Cerebral blood flow was unaffected, but mRNAs/miRNAs involved in mitochondrial function and metabolism were modulated by MgSO4. Metabolomic analysis (H+-NMR) disclosed that MgSO4attenuated HI-induced increases in succinate and prevented depletion of high-energy phosphates. MgSO4pretreatment preserved mitochondrial respiration, reducing ROS production and inflammation after HI. Therefore, we propose that MgSO4evokes preconditioning via induction of mitochondrial resistance and attenuation of inflammation.

Perinatal insults such as hypoxia-ischemia induces secondary brain injury. In order to develop the next generation of neuroprotective therapies, we urgently need to understand the underlying molecular mechanisms leading to cell death. The cell death mechanisms have been shown to be quite different in the developing brain compared to that in the adult. The aim of this review is update on what cell death mechanisms that are operating particularly in the setting of the developing CNS. In response to mild stress stimuli a number of compensatory mechanisms will be activated, most often leading to cell survival. Moderate-to-severe insults trigger regulated cell death. Depending on several factors such as the metabolic situation, cell type, nature of the stress stimulus, and which intracellular organelle(s) are affected, the cell undergoes apoptosis (caspase activation) triggered by BAX dependent mitochondrial permeabilzation, necroptosis (mixed lineage kinase domain-like activation), necrosis (via opening of the mitochondrial permeability transition pore), autophagic cell death (autophagy/Na(+), K(+)-ATPase), or parthanatos (poly(ADP-ribose) polymerase 1, apoptosis-inducing factor). Severe insults cause accidental cell death that cannot be modulated genetically or by pharmacologic means. However, accidental cell death leads to the release of factors (damage-associated molecular patterns) that initiate systemic effects, as well as inflammation and (regulated) secondary brain injury in neighboring tissue. Furthermore, if one mode of cell death is inhibited, another route may step in at least in a scenario when upstream damaging factors predominate over protective responses. The provision of alternative routes through which the cell undergoes death has to be taken into account in the hunt for novel brain protective strategies.

Screening and identifying multi-target ligands becomes a daunting task when there are very few matching pharmacophoric features among the proteins. Herein, we describe a novel screening strategy to identify multi-target ligands for proteins having varying pharmacophoric features with their ligands. This strategy was adopted to identify multi-target ligands for death-associated protein kinase (DAPk) family. The role of the kinase activity of DAPk in eukaryotic cell apoptosis and the ability of bioavailable DAPk inhibitors to rescue neuronal death after brain injury have made it a drug-discovery target for neurodegenerative disorders. In this work, we employed a novel strategy using the existing computational approaches to design multi-target inhibitors, which can potentially inhibit one or any combination of the three DAPk family members. The strategy employs a combination of merged pharmacophore matching, database screening and molecular docking to reliably identify potential multi-target inhibitors targeted against DAPk protein family.

Perinatal brain damage underlies an important share of motor and neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment, visual dysfunction and epilepsy. Clinical, epidemiological, and experimental studies have revealed that factors such as inflammation, excitotoxicity and oxidative stress contribute considerably to both white and grey matter injury in the immature brain. A member of the death associated protein kinase (DAPk) family, DAPk1, has been implicated in cerebral ischemic damage, whereby DAPk1 potentiates NMDA receptor-mediated excitotoxicity through interaction with the NR2BR subunit. DAPk1 also mediate a range of activities from autophagy, membrane blebbing and DNA fragmentation ultimately leading to cell death. DAPk mRNA levels are particularly highly expressed in the developing brain and thus, we hypothesize that DAPk1 may play a role in perinatal brain injury. In addition to reviewing current knowledge, we present new aspects of the molecular structure of DAPk domains, and relate these findings to interacting partners of DAPk1, DAPk-regulation in NMDA-induced cerebral injury and novel approaches to blocking the injurious effects of DAPk1.

Field observations suggest that ettringite-induced swell in lime-treated soils may manifest rapidly after placement and compaction or after months or even years after lime treatment. In either case, forensic investigations have identified the presence of the mineral ettringite in distressed sections. However, the time window between the observation of distress and the subsequent forensic evaluations has left room for doubt as to whether the ettringite caused the observed distress or was formed between the time of the observed distress and the time of the forensic investigation. The study focuses on identifying alternative, probable mechanisms of swelling when sulfate-laden soils are stabilized with lime. The research addresses the hypothesis that swelling in sulfate-bearing fine-grained soils results from one or a combination of three mechanisms: (a) volumetric expansion during ettringite formation, (b) water movement triggered by a high osmotic suction caused by sulfate salts, and (c) the ability of the ettringite mineral to absorb water and contribute to the swelling process. The data validate the conclusion that a synergy of the mechanisms discussed contributes to swelling distress. The study also addresses the impact of matrix strength of the stabilized soil on damage potential.

Civil engineers are at times required to stabilize sulfate-bearing clay soils with calcium-based stabilizers. Deleterious heaving in these stabilized soils may result over time. This paper addresses critical questions regarding the consequences of treating sulfate laden soils with calcium-based stabilizers. The authors describe the nature (chemistry and structure) of the minerals (ettringite/thaumasite) blamed for deleterious reactions and explain why these structures may lead to damage. The writers also describe the mechanisms of the mineral growth, and the extent of mineral growth based on the amount of sulfate minerals present in the soil. The writers explain why the rate of ettringite growth in treated soils should not be expected to follow a controlled rate of ettringite development such as that which normally occurs in portland cement concrete. The writers compare the rate and degree of ettringite development in soils to the classical model of nucleation and growth typical of most crystal structures. Finally, the writers evaluate the role of soil mineralogy in controlling soil behavior at varying sulfate contents and verify the existence of a threshold level of soluble sulfates in soils that can trigger substantial ettringite growth.

Damage in sulfate-bearing soils and aggregate systems stabilized with additives containing lime, including lime and portland cement, has drawn considerable attention over the past two decades. Researchers and practitioners have made considerable contributions to the understanding of the problem, including the mechanisms involved in the formation of the two minerals, ettringite and thaumasite, that are most often associated with this damage. This paper provides a case history analysis of the expansion history compared with the ettringite growth history of three controlled low-strength mixtures containing fly ash with relatively high sulfate contents. Samples were subjected to three curing conditions: a dry cure, in which only mixing water was available for curing; a moist cure, in which an external source of water was available for curing; and a sulfate cure, in which an external source of sulfate-bearing water was made available for the duration of cure. Ettringite was quantified by using both differential scanning calorimetry and X-ray diffraction; the resulting volume changes in the samples were measured. Results suggested that sorption of water by the ettringite molecule was at least part of the reason for expansion. The importance of sorption was based on the fact that although expansion increased in moist cure compared to dry cure systems, the quantities of ettringite formed under each regime were about the same and remained about the same throughout the experiments. As expected, samples exposed to sulfate cure responded with the greatest expansion, which was concomitant with continued ettringite crystal growth due to a supply of the limiting reagent, sulfate.

Considerable attention has been given to sulfate-induced heave in soils stabilized with calcium-based stabilizers over the past two decades. Empirical evidence has supported threshold values of water-soluble sulfates that are used as guidelines to define the risk of distress. This study uses two approaches to evaluate these sulfate threshold values as well as to compare the sensitivity of soils with different mineralogies to sulfate-induced damage. Five soils, each belonging to a different soil series and with significantly different chemistries and mineralogies, are evaluated. Differential scanning calorimeter and stoichiometric mass balance calculations based on a thermodynamics-based phase diagram approach are used to evaluate the influence of mineralogy on soil behavior. The variation in sensitivity of different soils to ettringite formation was substantiated and was found to be dependent on reactive clay content in the soil. Although the sensitivity of soils to ettringite formation was observed to change with the availability of reactive clay fractions, no definitive relationship was established between clay content and weight percentage of ettringite formed. The empirical threshold of about 3,000 ppm is generally substantiated as is the efficacy of the concept of extended mellowing periods with homogeneous mixing while adding as much mixing water as possible. Finally, a general agreement between the mass balance predictive approach and the direct measurement by using the differential scanning calorimeter was established.

Background: Osteopontin (OPN) is a highly phosphorylated sialoprotein and a soluble cytokine that is widely expressed in a variety of tissues, including the brain. OPN and OPN-derived peptides have been suggested to have potential neuroprotective effects against ischemic brain injury, but their role in preterm brain injury is unknown. Methods: We used a hypoxia-ischemia (HI)-induced preterm brain injury model in postnatal day 5 mice. OPN and OPN-derived peptides were given intracerebroventricularly and intranasally before HI. Brain injury was evaluated at 7 days after the insults. Results: There was a significant increase in endogenous OPN mRNA and OPN protein in the mouse brain after the induction of HI at postnatal day 5. Administration of full-length OPN protein and thrombin-cleaved OPN did not affect preterm brain injury. This was demonstrated with both intracerebroventricular and intranasal administration of OPN as well as in OPN-deficient mice. Interestingly, both N134–153 and C154–198 OPN-derived peptides increased the severity of brain injury in this HI-induced preterm brain injury model. Conclusions: The neuroprotective effects of OPN are age-dependent, and, in contrast to the more mature brain, OPN-derived peptides potentiate injury in postnatal day 5 mice. Intranasal administration is an efficient way of delivering drugs to the central nervous system (CNS) in neonatal mice and is likely to be an easy and noninvasive method of drug delivery to the CNS in preterm infants.

Forkhead box (Fox) proteins are a superfamily of evolutionarily conserved transcriptional regulators, which control a wide spectrum of biological processes. FoxG1 is a transcriptional repressor, whose function has been elucidated recently. FoxG1 overexpression was found to be associated with medulloblastoma and hepatoblastoma. It was suggested that the inhibition of FoxG1 could be a potential target for the development of molecular therapeutics in such type of cancers. Since, experimentally derived structure for FoxG1 is unavailable in any of the structural databases, modeling of the DNA binding domain of this protein was carried out. Potential binding sites on the protein surface were predicted. Pharmacophoric features were derived from the binding site that lies near the protein-DNA binding interface and this pharmacophore was employed for virtual screening of compounds. To the best of our knowledge, this is the first pharmacophore model proposed for screening inhibitors of FoxG1, which may interfere with its transcriptional repressor functionality. The interactions of the binding site residues with the top scoring ligand hits were analyzed. These ligands may be used for the development of potential inhibitors of FoxG1 protein.

Ischemic stroke is the second leading cause of death and long-term disability worldwide, for which no effective therapies are available. The increasing prevalence of ischemic stroke and related health risks, combined with the lack of effective therapies, highlight the desperate need for continued research for exploring the safe and effective drugs, which favourably influence multiple pathways leading to neuroprotection and extend the benefit to a larger number of patients diagnosed with stroke. Numerous preclinical studies have reported very promising results using "neuroprotectants", all of which have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to specific areas of the brain is restricted by the blood-brain barrier (BBB). Nanoparticles (NPs) have colossal applications that could revolutionize the treatment of ischemic stroke. NPs can readily transmigrate across the BBB without compromising its integrity. Recent striking developments in nanotechnology have produced a great deal of nano-devices, which could be used for the treatment and neuronal regeneration following ischemic stroke. This article attempts to convey the untapped potentials of nanopharmaceuticals for the treatment of ischemic stroke. Looking towards the future, this review focuses on the potential applications of nanoparticulate systems for the delivery of therapeutic cargo into the brain for imparting neuroprotection against ischemic stroke. This review also provides an overview of targeted NPs, which are being used for imaging, neuroprotection and regeneration of ischemic brain.

Histone deacetylases (HDACs) are enzymes that modify chromatin structure and contribute to aberrant gene expression in cancer. A series compounds with well-assigned HDAC inhibitory activity was used for docking based 3D-QSAR analysis. The 3D-QSAR acquired had excellent correlation coefficient value (q^2=0.753) and high Fisher ratio (F=300.2). A validated pharmacophore model (AAAPR) was employed for virtual screening. After manual selection, molecular docking and further refinement, six compounds with good absorption, distribution, metabolism, and excretion (ADME) properties were selected as potential HDAC inhibitors. Further, the molecular interactions of these inhibitors with the HDAC active site residues were discussed in detail.

Practicing engineers are at times required to ameliorate or stabilize sulfate-bearing soils that exhibit sulfate-induced heave when treated with lime. Cost effectiveness of stabilization and amelioration techniques can be improved by using geologic models that identify the factors and processes that control the distribution of sulfate through the landscape. The paper describes the use of geospatial data sets, direct measurements of soil conductivity, and geochemical modeling to develop a geologic model of sulfate distribution along the SH-130 corridor in Texas. These geologic models can effectively be used to define the risk associated with sulfate-induced heave in soils that are encountered during construction. The technique can also be used to focus sampling and testing to the high-risk locations and thereby contributing to the economic success of the project. The sensitivity of soils to form ettringite/thaumasite with increasing sulfate concentration can also be evaluated using these geologic models.