Abstract: Background: Trauma is the leading cause of morbidity and mortality in young patients, acute surgical conditions cause morbidity and mortality in patients of all ages. Computed tomography scan (CT) assist greatly in the investigation and management of these patients with blunt and penetrating trauma, facilitating early diagnosis and expedites early appropriate treatment of these patients. Acute non-traumatic surgical conditions also mimic non-surgical pathologies and differentiating the two is important because management is different and any delay in surgical intervention results in high morbidity and some may even result in mortality. Method: Literature review of the role of multidetector CT scan (MDCT) in managing acute surgical emergencies and trauma-diagnosis in the trauma patient and patients presenting with acute surgical emergencies. The focus is on the role of the MDCT in the management of these patients. Results highlight that the use of MDCT expedites management of these patients, allowing early surgical intervention and preventing unnecessary surgical interventions where the intervention is not indicated, based on the MDCT results. Conclusion: This paper emphasizes the important role that is played by the MDCT in the management of the above patients.

This article describes the history of research and development of surface-penetrating radar, starting from the 60s in the USSR, and ending today in Russia and neighboring states formed after the collapse of the USSR. The outstanding role played in the initial period of this technology development by Prof. M.I. Finkelstein and his colleagues is highlighted. Their research had a significant impact on subsequent developments in modern Russia and the neighboring countries.

When ground-penetrating radar is used to detect targets within concrete, the location of the targets, the identification of different shapes, properties and less obvious echoes all greatly increase the interpretation time of the staff and can easily cause misjudgment of the echo images. In this paper, the ground-penetrating radar echo images (B-scan) after processing are mean filtered to eliminate the direct waves that interfere greatly with the echoes. The RFB-s structure is added to the YOLOv3-SPP network structure, while the Anchor value is optimized and the EIOU loss function is introduced. For four types of data with different shapes and properties at random target locations, three models, YOLOv3, YOLOv3-SPP and the improved YOLOv3-SPP, are used for classification and identification, and the proposed algorithm models are comprehensively evaluated using model evaluation metrics. The experimental results show that the algorithm models proposed in this paper have good recognition effect in ground-penetrating radar echo image target detection.

Debris-flows are recurrent events on mountain- and hill- slopes, and they have been the object of numerous field investigations and sampling, however most of this work reposes on imagery and outcrop analysis, in such a way that there are still only a handful of studies investigating the internal architecture of these events’ deposits. In the present contribution, we aims at underneath the internal structure of a portion of a debris-flow deposit that was accessible in the aftermath of the 2018 heavy-rainfall debris-flows in Hiroshima Japan. Using a Ramac Pro-Ex GPR with 500 MHz and 800 MHz antenna, a set of longitudinal and transversal transects was used to characterize the deposit. The results demonstrated that a set of subhorizontal layers have filled the valley, and interacting with local terrace edges, these layers have piled up and overcome the obstacle. Across the valleys, a set of trough suggest the presence of channels that were also filled during the event. Finally, in the channel post-event, a set of radargram “cross-bedded units” shows that the final deposition in the channel was of a more dilute flow, typical of a Newtonian flow. This set of units was not to be found at the surface of the post-event pseudo-surface, suggesting that the flow ended as a debris-flow on this surface, and that it is only when the flow dug the final channel that the nature of the flow returned from debris-flow to Newtonian flow.

The paper presents experimental studies on the geophysical survey of Almaty – Nur-Sultan highway sections, which located 100 km. from Almaty, Almaty region of the Republic of Kazakhstan. As the object of study selected highway sections in 3 places: on the highway section with a well-preserved coating to identify layers; on the highway section with obvious damage (with holes, potholes, horizontal and grid cracks); on the section of the highway with a drainage pipe. Since the formulation of the problem requires the use of a non-destructive, fast method that gives an idea of the layer structures with an accuracy of ± 0.1 m., experimental studies were conducted using the ground penetrating radar (GPR) «Loza B» using different antennas, with different profile steps for accuracy. The results of the geophysical survey of the structure of the underlying layers and asphalt for the detection of defects and their causes are presented. The results of this work can be used to develop compositions of asphalt concrete mixtures with high temperature stability, strength and durability, considering the climatic conditions in order to ensure the safety of road surfaces during operation.

This paper provides a comparative study between microwave tomography and synthetic time-reversal imaging techniques as applied to ground penetrating radar (GPR) surveys. The comparison is carried out by processing experimental data collected at a controlled test site, with various types of buried targets at given subsurface depths and representative soil conditions. It is shown that the two techniques allow us to obtain complementary information about position, depth and size of the targets from a single GPR survey.

The main goal of the research is to assess the effectiveness of aerial ground-penetrating radar (GPR) in delineating boundaries between disturbed clayey ground and rock formations along the old Wadi. The study also tackles technical challenges associated with drone-based GPR applications in urban open areas, considering geological heterogeneity, topographic variations, and environmental conditions. The potential of using drone-based GPR equipped with an unshielded dipole antenna as a transformative tool in geospatial analysis was demonstrated. The research encompasses academic insights and field borehole drilling experiments to validate the accuracy and reliability of drone-based GPR data in real-world scenarios. Anticipated contributions include advancements in understanding drone-based GPR technology for mapping disturbed soil boundaries in foundation engineering applications and other relevant areas and recommendations for optimizing its performance in challenging terrains.

In this study, an experiment was conducted on hoop pine (Araucaria cunninghamii), which is a common tree species in Taiwan. Holes with diameters of 4, 5, 7, 10, 12, and 14 cm were drilled in dry hoop pine timber with a diameter of 39 cm and a height of 57 cm, and an 800 MHz Ground Penetrating Radar (GPR) antenna were used to determine the minimum image resolution and the size of the holes in the wood. GPR images of the timber were subjected to a filtering process to obtain characteristic reflection curves of the damage to the timber. Curves with clear waveforms were observed in the GPR profiles of eccentric holes with a diameter of 4 cm. Profiles of the damage were obtained and profile images with the trunk radius at the centre were transformed into polar coordinate images. From these polar coordinate images, the location, size and diameter of the eccentric holes in the wood were identified, and the reflection curves were characterised by waveforms and irregular fluctuations. The risk levels of tree trunks were determined on the basis of their t/R (minimum normal wall thickness of the cross-section of the trunk/radius of the trunk) values and hole area ratios. A comparison between the GPR-based results and the actual diameters of the holes revealed that the filtered GPR profiles could be used for the efficient and accurate assessment of damage to hoop pine timber (average error rate ≤ 4%).

As mitochondria are negatively charged organelles, penetrating cations are used as a part of the chimeric molecules to deliver the specific compounds into mitochondria. However, unmodified penetrating cations affect different aspects of cellular physiology as well. In this review we have attempted to summarize the data about side effects of the commonly used natural (e.gberberine) and artificial (e.g. tetraphenylphosphonium, rhodamine, methylene blue) penetrating cations on cellular physiology. For instance, it was shown that such types of molecules can (1) facilitate proton transport across membranes; (2) react with redox groups of respiratory chain; (3) induce DNA damage; (4) interfere with pleiotropic drug resistance; (5) disturb membrane integrity (6) inhibit the enzymes. Also, the products of the biodegradation of penetrating cations can be toxic. As penetrating cations accumulate in mitochondria, their toxicity is mostly due to the mitochondrial damage. Mitochondria of certain types of cancer cells appear to be especially sensitive to penetrating cations. Here we discuss the molecular mechanisms of the toxic effects and the anti-cancer activity of the penetrating cations.

Regulatory T cell master transcription factor, Forkhead box P3 (Foxp3) has been detected in cancer cells, but its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumor administration of Ad.P60 in breast tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells, and that gene therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

In 2020, the WHO established a road map for neglected tropical diseases 2021−2030 that aims to control and eradicate 20 diseases, including Leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions such as those caused by Trypanosoma cruzi and Leishmania spp infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, avoiding the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes, as well as to stimulate the host immune defenses or even serve as a vector of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of Leishmaniosis and Chagas disease.

Pythium insidiosum(PI) can cause sight threatening keratitis which is managed commonly by performing penetrating keratoplasty. This article is a retrospective review to assess outcomes of keratoplasty performed in patients diagnosed with PI keratitis. (2) Methods: Pre-operative, intra operative and post-operative data of patients diagnosed with PI keratitis and who underwent keratoplasty for their condition from January 2020 to December 2021 were col-lected from the central patient database of a tertiary eye care hospital in India. The data were an-alyzed for anatomic success, elimination of infection, graft survival, incidence of repeat kerato-plasty, final visual acuity and varied complications. (3) Results: In total, 16 eyes underwent pene-trating keratoplasty for PI keratitis during the study period. Mean time to keratoplasty from on-set of symptoms was 31.3 days and mean graft size was 10.4 mm. Nine out of the 16 cases had recurrence of infection following surgery, six of which required a repeat keratoplasty for elimina-tion of infection. Out of these 6 patients, one patient underwent 2 repeat keratoplasties. Mean graft size for repeat keratoplasty performed in recurrent cases was 11.7 mm. Globe was successfully salvaged in 14 out of 16 patients (87.5 %). Endo-exudates, graft infiltration, graft dehiscence, secondary glaucoma and retinal detachment were the various complications noted after kerato-plasty. (4) Conclusion: Keratoplasty remains the choice of treatment in PI keratitis, however re-currence of disease and graft failure are common. Large sized grafts, meticulous per-operative removal of infection, adjuvant cryotherapy, and intraoperative and post-operative use of antibi-otics can help in improving outcome of keratoplasty in these patients.

Desertification and dune progression over vegetation is quantified using remote sensing data, but vegetation, eventually temporarily, buried under sand blowout may escape such assessment, and to estimate the extent of buried vegetation, a GPR campaign was conducted over the coastal sand-dune of Tottori Prefecture (Japan) in combination with a high-resolution topographic UAV-based survey of the topography. The result shows that buried vegetation exists underneath sand-blowout, especially near the dune ridges, and that this vegetation can extend 20 – 30 m further than the estimation made from airborne remote sensing. Furthermore, the presence of palaeo-vegetation in palaeodune layers also provide information on the long-term evolution of sand dunes (with periods of stability vs rapid change), which can be used to reconstruct Quaternary coastal environments.

Cell-penetrating peptides (CPPs) have been evaluated as enhancers in drug delivery, their addition in medical formulations favors absorption allowing obtaining the pharmacological effect with lower drug doses. In vaccine formulations their inclusion has been also explored with interesting results. Currently mucosal vaccination constitutes a promising alternative with the main advantage of inducing both systemic and mucosal immune responses, which are crucial for control tumors and infections at mucosal tissues. The known CPP Penetratin was recently evaluated in vaccine formulations designed for nasal administration. The authors demonstrated that this non-covalent linked CPP could improve the antigen-specific systemic and mucosal antibody responses. In the present work we evaluate in Balb/C mice the nasal immune-enhancing effect of four CPPs. Animals were intranasally immunized with CPP and the recombinant hepatitis B surface protein (HBsAg) as model antigen. The IgG antibody response in sera and the mucosal IgA response were measured by ELISA. The IFN-g secretion response at spleen was also evaluated by ELISPOT and ELISA. Among the CPPs studied one novel peptide stand out by its ability to potentiate the humoral and cellular immune response against the co-administered antigen. Considering that the use of mucosal routes is a promising strategy in vaccination against infectious diseases and cancer, which are gaining special relevance nowadays in the development of novel candidates against SARS-CoV-2 and other potential emerging respiratory virus, the searching and development of safe mucosal adjuvants constitute a current need.

Cell junction that is usually associated with dynamic cytoskeletons is essential for a wide range of cellular activities such as cell migration, cell communication, barrier function and signal transduction. Real-time observation of cell junction facilitates understanding of the mechanisms by which cell junction regulate relevant cellular activities. In this study, we examined the binding capacity of a modified tridecapeptide from Cx43 to cell junction protein ZO-1 and sought to create a fluorescent peptide that could be used to label cell junction. To introduce the fluorescent peptide into the cells, a cell-penetrating peptide was linked to the modified tridecapeptide and synthesized. The binding of the modified tridecapeptide was tested using pull down and immunoprecipitation assay. The ability of the peptide to label cell junction was assessed by adding it to fixed or cultured Caco-2 cells. Testing assay revealed that the Cx43-derived peptide can bind to ZO-1. Besides, the peptide was able to label cell junction of fixed cell, although no obvious cell junction labeling was observed clearly in living cells, probably due to the inadequate affinity. These results indicate that a peptide-based strategy for labeling cell junction may be feasible, and efforts to improve its affinity are warranted in the future.

The CRISPR/Cas9 gene editing system has enormous potential in the treatment of multiple genetic disorders. To fully harness this potential, it is essential to deliver CRISPR-Cas9 components safely and effectively into the nuclei of target cells. In this study, we tested the amphipathic cell-penetrating peptide LAH5, previously used for DNA delivery, to intracellularly deliver spCas9: sgRNA ribonucleoprotein (RNP) and RNP/single-stranded homology-directed repair (HDR) template. We discovered that the LAH5 peptide effectively formed nanocomplexes with both RNP and RNP/HDR cargo, and that these nanocomplexes were taken up by cells effectively. Peptide/RNP nanocomplexes were characterized for size and charge, and nanocomplexation with RNP and RNP/HDR cargo was demonstrated via an electrophoretic mobility shift assay. Various ratios of peptide/RNP nanocomplexes were functionally screened on fluorescent reporter cell lines for gene editing and HDR-mediated gene correction. Additionally, targeted gene editing of the CCR5 gene was demonstrated in various cell lines. This LAH5-based delivery strategy paves the way for the development of therapeutic delivery systems for CRISPR/Cas-based genomic engineering.

In this work, we studies the principle of ground electrode current field through ground communication technology, signal design, and optimal working mode of excitation source, so as to adapt the working mode, working frequency, and transmission medium condition of signal transmission. Through waveform design, energy is concentrated in the main conduction direction, which is beneficial for signal filtering at the receiving end and achieving high reliability data transmission; On this basis, on-site environmental testing was conducted to verify the detection and recognition technology of weak signals. Signal design and detection recognition are a very important part of the grounding electrode current field through ground communication technology. The grounding electrode current field through ground communication technology is mainly applied to solve the problem of communication between rescue personnel and trapped personnel before and during tunnel engineering collapse and rescue.

Exploring new ways to represent and discover organic molecules is critical for developing novel therapies. With recent advances in bioinformatics, virtual screening of databases is possible. However, biochemical data must be encoded using computer algorithms to make them machine-readable, taking into account distance and similarity measures to support tasks such as similarity searching. Motivated by the ubiquity of the carbon element and the structured patterns that emerge, we propose a parametric approach to molecular encodings of carbon-based multilevel atomic neighborhoods. It implements a walk along the carbon chain of an organic molecule to compute different representations of its feature encoding in the form of a binary or numerical array that can be exported later into an image. Resulting encodings are reproducible and readily formatted for various domain tasks including machine learning tasks. This approach was evaluated using a 10-fold stratified cross validation for binary classification with eight data sets and six different encodings (384 models) in the domain knowledge of cell-penetrating peptides. The parametric approach is built on open-source software and is implemented as a Python package (cmangoes). Source code and documentation are available at https://github.com/ghattab/cmangoes.

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

The UNESCO World Heritage Hadrian’s Villa lies over the Colli Albani volcanic district near Rome. Magnetic, paleomagnetic, radar, and electric resistivity surveys were performed in the Plutonium–Inferi sector to detect buried buildings and outline a segment of the underground system of tunnels that link different zones of the villa. In particular, a paleomagnetic analysis of the bedrock unit allowed to accomplish an accurate geomagnetic field modelling and characterize the archaeological sources of the magnetic field anomalies. We used a computer-assisted forward modelling procedure to generate a structural model of the sources of the observed anomalies. The intrinsic ambiguity of the magnetic field modelling was reduced with the support of ground penetrating radar amplitude slices and an analysis of radar and electric resistivity profiles. The bedrock lithology in this area is an ignimbrite tuff characterized by abundant iron oxides. The high-amplitude magnetic anomalies observed in the Plutonium–Inferi area are due to strong bedrock remnant magnetization and susceptibility contrasts between topsoil infill of cavities and the surrounding tuff. The resulting magnetization model of the Plutonium–Inferi complex shows that the observed anomalies are mostly due to the presence of tunnels, skylights and a system of ditches excavated in the tuff.

This paper deals with bistatic subsurface probing of a horizontally layered dielectric half-space by means of ultra-wideband electromagnetic pulses. A receiver collects reflections from the air-ground interface and from the gradients of dielectric permittivity in the half-space. This scenario is of interest for ground penetrating radar (GPR) applications. For the analytical description of the received signal, we developed and implemented a novel time-domain version of the coupled-wave Wentzel–Kramers–Brillouin approximation. Our solution is in very good agreement with finite-difference time-domain results, radically accelerates calculations, and effectively accounts for the protracted return signals observed in the lower part of the GPR spectrum. The paper includes results showing the application of the proposed technique to two case studies: in particular, the method was employed for the post-processing of experimental radargrams collected on Lake Chebarkul, in Russia, and to simulate GPR probing of the Moon surface, to detect smooth gradients of the dielectric permittivity in lunar regolith.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

A new algorithm is developed in this study to automatically detect reinforced concrete structures' rebar locations and diameters using the ground penetrating radar technique. The method approximates the hyperbolic signatures using two-way travel time and bi-quadratic equations. The study includes formulating electromagnetic wave speed in reinforced concrete (RC) structures. The algorithm was used in a computer code to provide an automated analysis of ground-penetrating radar data collected from a pre-planned survey grid. Two RC slabs were fabricated and tested to validate the proposed method. The proposed method is efficient in signal processing and accurately and reliably determining the rebar information.

Despite great strides in diagnosis and treatment, cardiac diseases remain the number one cause of mortality in the developed world, with rates catching up at an alarming rate in the developing world. Targeted delivery of therapeutics, specifically to cardiomyocytes, would open up new frontiers. Our prior work using a combinatorial in vitro and in vivo phage display methodology identified a 12-amino acid long peptide that targets cardiomyocytes selectively after an intravenous injection in as little as 5 mins, and hence was termed cardiac targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension for development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed on the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10µM of Cyanine-5.5 labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by more extensive studies performed by Eurofins in stably transfected cell lines for an extensive list of GPCR-coupled receptors. Positive data for GPCR-coupled receptors was interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting 60, 6-week-old, wild-type CD1, male/female mice (1:1) injected with CTP (150 µg/Kg) intravenously. Mice were weighed immediately before injections and daily thereafter. Cohorts of mice were euthanized on day 0, 1, 2, 7 and 14 with inhalational CO2, followed by opening of the chest cavity, collection of blood via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after injections of CTP (150 µg/Kg) to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. In the Eurofins Cardiac Profiler Qube, no significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed by RT-qPCR. There was no change in blood pressures before and after injections with CTP at 10 mg/Kg. Blood counts and chemistries showed no evidence of significant hematological, hepatic or renal toxicities. Lastly, there was no significant difference in cardiac function, size or mass before and after CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies, in good laboratory practices fashion, are needed with more prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell penetrating peptides (CPP) are 5-30 amino acid long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood-brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell or tissue specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for myriad different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outlining its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.

Djeya1 (RKLAFRYRRIKELYNSYR), is a very effective cell penetrating peptide (CPP) which mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species variable sites: 10,13,16. CD analyses indicted that Djeya1 is highly helical and that Aib-substitution had little influence on secondary structure. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells which express high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblast are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation.

The active layer thickness (ALT) is affected by local soil material and surface vegetation coverage in Tibetan plateau permafrost region. The human activities and engineering construction along the Qinghai-Tibet Highway (QTH) destroyed the surface vegetation coverage, which have seriously influenced the ALT and heat exchange balance. Meanwhile, the changes of the detailed internal structure in the active layer will affect the stability of engineering infrastructure. Ground-penetrating radar (GPR) was used to detect the ALT in the permafrost region. However, researches on the detailed structure of the active layer and spatial variation information of ALT are rare, the main reason given for this is that the lack of advanced imaging techniques to enhance the GPR images. In this paper, the researchers focus on solving this problem by applying the reverse time migration (RTM) method to GPR field data acquired in the Beiluhe region. Analyses of the results led to conclusions as follows: a) The RTM algorithm is proved to be accurate for imaging the characteristics of the active layer through the dielectric constant model obtained by common midpoint and GPR data velocity analysis. b) The result of RTM profiles show the loose structure and graben-like fine internal structure. Combining with drill data and soil materials information, the researchers deduce the graben-like structure might be coarse gravel layer, which may be related to subgrade settlements in some local area. c) The 2D contour maps not only show the spatial variation feature of ALT at two sides of the highway, but also can compensate the defect of the research for single 2D survey line. The ALT is about 0.6~0.8 m in most areas, and about 0.8~0.9 m near the highway at west side of the QTH on the 2D contour maps. From the RTM interpretation profile, the closer to the plash, the deeper thawed active layer. The detailed internal structure of the active layer and 2D contour maps of ALT have great significance for the study of fine internal structure and the characteristic of ALT spatial variation in the Tibetan plateau under the background of climatic change.

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

Keywords: Antisense Oligonucleotides, Cell Penetrating Peptides, Delivery, DG9 peptide, Phosphorodiamidate morpholino oligomers (PMO), Pip, R6G.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

In this study, the shape and size of a combustion cavity with a fracture zone in the gasified coal seam was determined with use control boreholes and a ground-penetrating radar (BGPR) test. The underground coal gasification (UCG) field-scale experiment was performed in Carboniferous strata in coal seam 501 at a depth of approx. 460 m in the Wieczorek hard-coal mine in the Upper Silesian Coal Basin, Poland. After the termination of the UCG reactor, five coring boreholes were drilled to identify the geometry of the resulting combustion cavity and the impact of the UCG process on the surrounding rock mass. Borehole ground-penetrating radar measurements were performed using a 100 MHz antenna in three boreholes with a length of about 40-50 m. This enabled the identification of the boundaries of the combustion cavity and the fracture zone in the coal seam. The fracture zones of rock layers and lithological borders near the control borehole were also depicted. As a result, the cavity was estimated to have a length of around 32 m, a width of around 7 m and a height of around 5 m. The analyses performed with the control boreholes and the BGPR provided sufficient information to determine the geometry of the combustion cavity and the fracture zone.

Given the pathological role of hyperphosphorylated Tau aggregation in Alzheimer’s disease (AD) our laboratory previously developed the novel Tau aggregation inhibitor peptide, RI-AG03. As Tau aggregates accumulate intracellularly, it is essential that Tau-targeting peptides efficiently traverse the cell membrane. In addition, these peptides need to avoid sequestration into cell organelles, particularly those involved in degradation, to ensure interaction with Tau in the cytoplasm. Here, we examine the cellular uptake and intracellular trafficking of RI-AG03 when the peptide is unconjugated or linked to nanoliposome carrier particles. The impact of adding the cell penetrating peptide (CPP) sequences, polyarginine (polyR) and transactivator of transcription (TAT), to RI-AG03 was also characterised. Our data show that the conjugation of CPP-containing RI-AG03 to liposomes dramatically increases cellular liposomes uptake. The majority of this uptake occurs via direct cell penetration. However, we find that macropinocytosis is also an important mechanism for unconjugated and RI-AG03-polyR-conjugated, but not RI-AG03-TAT-conjugated, liposome uptake. In agreement with this macropinocytosis-mediated internalisation, liposome lipids localise to lysosomes and macropinosomes following cellular uptake. However, while unconjugated RI-AG03 peptides also localise to lysosomes, liposome conjugation prevents this localisation, with the peptide detaching from the liposomes at the cell surface and evading organelle entrapment. Overall, this study demonstrates that CPP sequences and nanoliposomes carriers enhance the intracellular delivery of RI-AG03, furthering the possibility of the peptide’s use in targeting Tau pathology in AD.

Subsurface drainage systems remove excess water from the soil profile thereby improving crop yields in poorly drained farmland. Knowledge of the position of the buried drain lines is important: 1) to improve understanding of leaching and offsite release of nutrients and pesticides, and 2) for the installation of a new set of drain lines between the old ones for enhanced soil water removal efficiency. Traditional methods of drainage mapping involve the use of tile probes and trenching equipment. While these can be effective, they are also time-consuming, labor-intensive, and invasive, thereby entailing an inherent risk of damaging the drainpipes. Non-invasive geophysical soil sensors provide a potential alternative solution. Previous research has focused on the use of time-domain ground penetrating radar (GPR), with variable success depending on local soil and hydrological conditions and the central frequency of the specific equipment employed. The objectives of this study were 1) to test the use of a stepped-frequency continuous wave (SFCW) 3D-GPR (GeoScope Mk IV 3D-Radar with DXG1820 antenna array) for subsurface drainage mapping, and 2) to evaluate the performance of a 3D-GPR with the use of a single-frequency multi-receiver electromagnetic induction (EMI) sensor (DUALEM) in-combination. The 3D-GPR system offers more flexibility for application to different (sub)surface conditions due to the coverage of wide frequency bandwidth. The EMI sensor simultaneously provides information about the apparent electrical conductivity (EC_a) for different soil volumes, corresponding to different depths. This sensor combination was evaluated on twelve different study sites with various soil types with textures ranging from sand to clay till. While the 3-D GPR showed a high success rate in finding the drainpipes at five sites (sandy, sandy loam, loamy sand, and organic topsoils), the results at the other seven sites were less successful due to limited penetration depth (PD) of the 3D-GPR signal. The results suggest that the electrical conductivity estimates produced by the inversion of EC_a data measured by the DUALEM sensor could be a useful proxy to explain the success achieved by the 3D-GPR in finding the drain lines. The high attenuation of electromagnetic waves in highly conductive media limiting the PD of the 3D-GPR can explain the findings obtained in this research.

The Mahuagou gold deposit is among the most important gold deposits in the core of Huangling Anticline. However, the geochemical exploration on the surface of the mining area presents challenges due to the thin overburde.This paper focuses on the overburden soil of Fengxiangshugou (FXS) – Mahuanggou (MHG) section as the research object, utilizes chemical form analysis of gold, soil halogen survey, and heat-released mercury survey to determine the key deep-penetrating geochemical methods for mining area. The results indicated that Si and Al components of samples exhibit minimal variation, suggesting that drift loads did not influence the overburden soil. Based on the systematic clustering, As, Sb, Mo, Bi, W and Hg emerge as ore-body or ore-belt front elements of hydrothermal gold deposits. In the study area, the predominant chemical form of gold in soil is the strong organic bond. Compared to the total amount, strong organic bound gold and heat-released mercury show higher anomaly contrasts, making them crucial indicators of faults, intrusions and hidden ore bodies. Consequently, chemical form analysis of gold and heat-released mercury surveys can enhance the anomaly contrast, proving beneficial for geochemical prospecting for weak anomalies in this area.

Holographic subsurface radar (HSR) is currently not in widespread usage. This is due to an historical perspective in the ground penetrating radar (GPR) community that the high attenuation of electromagnetic waves in most media of interest, and the inability to apply time-varying gain to the continuous wave (CW) HSR signal precludes sufficient effective penetration depth. While it is true that the fundamental physics of HSR, with its use of a CW signal, does not allow amplification of later (i.e. deeper) arrivals in lossy media (as is possible with impulse subsurface radar — ISR), HSR has distinct some distinctive advantages. The most important of these is the ability to do shallow subsurface imaging with a resolution that is not possible with ISR. In addition, the design of an HSR system is simpler than for ISR due to the relatively low-tech transmitting and receiving antennae. This paper provides a review of the main principles of HSR through an optical analogy and describes possible algorithms for radar hologram reconstruction. We also present a review of the history of development of systems and applications for HSR of the “RASCAN” type which is possibly the only holographic subsurface radar that is produced in lots. Among the subsurface imaging and remote sensing applications considered are humanitarian demining, construction inspection, surveys of historic architecture and artworks, nondestructive testing of dielectric aerospace materials, security applications, paleontology, detection of wood-boring insect damage, and others. Each application is illustrated with relevant data acquired in laboratory and/or field experiments.

Holographic subsurface radar (HSR) is currently not in widespread usage. This is due to an historical perspective in the ground penetrating radar (GPR) community that the high attenuation of electromagnetic waves in most media of interest, and the inability to apply time-varying gain to the continuous wave (CW) HSR signal precludes sufficient effective penetration depth. While it is true that the fundamental physics of HSR, with its use of a CW signal, does not allow amplification of later (i.e. deeper) arrivals in lossy media (as is possible with impulse subsurface radar — ISR), HSR has distinct some distinctive advantages. The most important of these is the ability to do shallow subsurface imaging with a resolution that is not possible with ISR. In addition, the design of an HSR system is simpler than for ISR due to the relatively low-tech transmitting and receiving antennae. This paper provides a review of the main principles of HSR through an optical analogy and describes possible algorithms for radar hologram reconstruction. We also present a review of the history of development of systems and applications for HSR of the “RASCAN” type which is possibly the only holographic subsurface radar that is produced in lots. Among the subsurface imaging and remote sensing applications considered are humanitarian demining, construction inspection, surveys of historic architecture and artworks, nondestructive testing of dielectric aerospace materials, security applications, paleontology, detection of wood-boring insect damage, and others. Each application is illustrated with relevant data acquired in laboratory and/or field experiments.

Many fields of human activity benefit from the ability to create images of obscured objects placed behind walls and to map their displacement in a noninvasive way. Usually, imaging devices like Synthetic Aperture Radars (SAR) and Ground Penetrating Radars (GPR) use expensive dedicated electronics which results in prohibitive prices. This paper presents the experimental implementation and the results obtained from an imaging system capable of performing SAR imaging and interferometric displacement mapping of targets located behind walls, as well as 3D GPR imaging using a low-cost general-purpose radar sensor. The proposed solution uses for the RF section of the system a K-band microwave radar sensor module implementing Frequency Modulated Continuous Wave operation. The low-cost sensor was originally intended for simple presence detection and ranging for domestic applications. The proposed system was tested in several scenarios and proved to operate as intended for a fraction of the cost of a commercial imaging device.

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic vasculature forming in the regenerating tissues has a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine