The efficacy of weed management depends on the correct control timing according to the seedling emergence dynamics. Since soil temperature and soil moisture are two main factors that determine weed germination, the hydrothermal time model can be used to predict their emergence. The aim of this study was to estimate the base temperature (Tb) and base water potential (Ψb) for germination of Chenopodium album, Amaranthus retroflexus, Setaria pumila and Panicum capillare collected from fields in continental Croatia and then to compare these values with those of Italian populations embedded in the AlertInf model. Germination tests were performed at seven constant temperatures (ranging from 4 to 27°C) and eight water potentials (0.00 to - 1.00 MPa). Estimated Tb and Ψb were 3.4°C, -1.38 MPa for C. album, 13.9°C, -0.36 MPa for A. retroflexus, 6.6°C, -0.71 MPa for S. pumila and 11.0°C, -0.87 MPa for P. capillare, respectively. According to the criterion of overlap of the 95% confidence intervals, only Tb of C. album, and Ψb of A. retroflexus were similar between Croatian and Italian populations. Further field experiments should be conducted in the Croatian field to monitor weed emergence patterns of C. album and to calibrate the AlerInf equation parameters.

This research was conducted on the Maribaya Timur school community in Lembang Subdistrict, West Bandung Regency, Indonesia, which is an active community in the area that is threatened by the potential for earthquake disasters due to the active Lembang fault. Disaster risk reduction efforts are pursued through increasing school-based preparedness that involves members of the school community, surrounding communities and various institutions that are associated with reducing the risk of school-based earthquake. Increasing preparedness against earthquakes focuses more on aspects of capacity building of school communities in reducing disaster risk, while aspects of vulnerability and threats have not been the focus of disaster risk reduction. The steps taken refer to the element of preparedness by aligning with the conditions, needs and potential that exist in the school community. Theoretically, if the school community has preparedness to face an earthquake disaster, the risk of earthquake disaster in the school community will be reduced so that it can minimize losses, victims and suffering that will be caused by the earthquake disaster.

Multiplex genome editing may induce genotoxicity and chromosomal rearrangements due to double-strand DNA breaks at multiple loci simultaneously induced by programmable nucleases, including CRISPR/Cas9. However, recently developed base-editing systems can directly substitute target sequences without double-strand breaks. Thus, the base-editing system is expected to be a safer method for multiplex genome-editing platforms for livestock. Target-AID is a base editing system composed of PmCDA1, a cytidine deaminase from sea lampreys, fused to Cas9 nickase. It can be used to substitute cytosine for thymine in 3-5 base editing windows, 18 bases upstream of the protospacer-adjacent motif site. In the current study, we demonstrated Target-AID-mediated base editing in porcine cells for the first time. We targeted multiple loci in the porcine genome using the Target-AID system and successfully induced target-specific base substitutions with up to 63.15% efficiency. This system can be used for the further production of various genome-engineered pigs.

A random variable X that is base b Benford will not in general be base c Benford when c is not equal to b. This paper builds on two of my earlier papers and is an attempt to cast some light on the issue of base dependence. Following some introductory material, the “Benford spectrum” of a positive random variable is introduced and known analytic results about Benford spectra are summarized. Some standard machinery for a “Benford analysis” is introduced and combined with my method of “seed functions” to yield tools to analyze the base c Benford properties of a base b Benford random variable. Examples are generated by applying these general methods to several families of Benford random variables. Berger and Hill's concept of “base-invariant significant digits” is discussed. Some potential extensions are sketched.

A series of novel indole Schiff base derivatives (2a–2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using FT-IR, ¹H NMR, ¹³C NMR, andHR-MS. In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusarium moniliforme (F. moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 μg/mL against F. graminearum, F. oxysporum, F. moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 μg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

Abstract Thyroid diseases have a complex and multifactorial aetiology. Despite the numerous studies on the signals referable to the malignant transition, still remain elusive the molecular mechanisms concerning the role of oxidative stress. Based on its strong oxidative power, H2O2 could be responsible for the high level of oxidative DNA damage observed in cancerous thyroid tissue and hyper-activation of mitogen-activated protein kinase (MAPK), and PI3K/Akt, that mediate ErbB signaling. Increased levels of 8-oxoG DNA adducts have been detected in the early stages of thyroid cancer. These DNA lesions are efficiently recognized and removed by the base excision repair (BER) pathway initiated by 8-oxoG glycosylase1 (OGG1). This study investigated the relationship between the EGFR and OGG1-BER pathways and their mutual regulation following oxidative stress stimulus by H2O2 in human thyrocytes. We clarified the modulation of ErbB receptors and their downstream pathways (PI3K / Akt and MAPK / ERK) under oxidative stress (from H2O2) at the level of gene and protein expression, according to the mechanism defined in a non-pathological cell system, Nthy-ori 3-1. Later, on the basis of the obtained results of gene expression cluster analysis in normal cells, we assessed the dysregulation of the relationships in a model of papillary thyroid cancer with RET/TPC rearrangement (TPC-1). Our observations demonstrated that a H2O2 stress may induce a physiological cross-regulation between ErbB and OGG1-BER pathways in normal thyroid cells (while this is dysregulated in the TPC-1 cells. Gene expression data also delineated that MUTYH gene could play a physiological role in cross-talk between ErbB and BER pathways and this function is instead lost in cancer cells. Overall our data about OGG1 protein expression suggest that the alternative splicing mechanisms may lead to different protein isoforms, physiologically regulated in response to ErbB modulation, and that these could be dysregulated in the progression of thyroid malignancies with RET/TPC rearrangement.

Most human genetic disease arises from point mutations. These genetic diseases can theoretically be corrected by gene therapy but clinic practice is still far from mature. Nearly half of the pathogenic single-nucleotide polymorphisms (SNPs) are caused by G:C>A:T or T:A>C:G base changes. The best current methods to repair these changes are by base editing without footprint using recently developed CRISPR-Cas9 technology by David Liu’s lab. These base editing methods have been confirmed with precision and efficiency in cultured mammalian cells, but it is barely confirmed and the efficiency is still very low. Animal models are important in dissecting pathogenic mechanism for human genetic diseases and efficacy testing of base correction in vivo. Cytidine base editor BE4 is a newly developed version of cytidine base editing system that converts cytidine (C) to uridine (U) in cultured mammalian cells but has not been proven in vivo. In this study, we have tested this system in cells to inactivate GFP gene and in mice by introducing single-base substitution that leads to a stop codon in tyrosinase gene. High percentage albino coat-colored mice were obtained from black coat-colored donor zygotes after pronuclei microinjection. Sequencing results showed that expected base changes were obtained with high precision and efficiency (56.25%). There are no off-targeting events identified in predicted off-target sites. Results confirm BE4 system can work in vivo with high precision and efficacy, and has great potentials in clinic to repair human genetic mutations.

Quantitative measurements of performance parameters has the potential to increase consistency and enhance performance of the surfaces as well as to contribute to the safety of horses and riders. This study investigates how factors known to influence the performance of the surface, incorpo-ration of a drainage package, control of the moisture control, and introduction of a geotextile reinforcement, affect quantitative measurements of arena materials. The measurements are made by using affordable lightweight testing tools which are readily available or easily constructed. Sixteen boxes with arena materials at a consistent depth were tested with the Going Stick (GS), both penetration resistance and shear, the impact test device (ITD), and the rotational peak shear device (RPS). Volumetric moisture content (VMC %) was also tested with time-domain reflectometry (TDR). Results obtained using GS, RPS, ITD, and TDR indicate that the presence of the drainage package, moisture content, and geotextile addition were detected. Alterations due to combinations of treatments could also be detected by GS, ITD, and TDR. While the testing showed some limi-tations of these devices, the potential exists to utilize them for quality control of new installations as well as for the monitoring of maintenance of the surfaces.

Global population is predicted to approach 10 billion by 2050, an increase of over 2 billion from today. To meet the demands of growing, geographically and socio-economically diversified nations, we need to diversity and expand agricultural production. This expansion of agricultural productivity will need to occur under increasing biotic, and environmental constraints driven by climate change. Clustered regularly interspaced short palindromic repeats-site directed nucleases (CRISPR-SDN) and similar genome editing technologies will likely be key enablers to meet future agricultural needs. While the application of CRISPR-Cas9 mediated genome editing has led the way, the use of CRISPR-Cas12a is also increasing significantly for genome engineering of plants. The popularity of the CRISPR-Cas12a, the type V (class-II) system, is gaining momentum because of its versatility and simplified features. These include the use of a small guide RNA devoid of trans-activating crispr RNA (tracrRNA), targeting of T-rich regions of the genome where Cas9 is not suitable for use, RNA processing capability facilitating simpler multiplexing, and its ability to generate double strand breaks (DSB) with staggered ends. Many monocot and dicot species have been successfully edited using this Cas12a system and further research is ongoing to improve its efficiency in plants, including improving the temperature stability of the Cas12a enzyme, identifying new variants of Cas12a or synthetically producing Cas12a with flexible PAM sequences. In this review we provide a comparative survey of CRISPR-Cas12a and Cas9, and provide a perspective on applications of CRISPR-Cas12 in agriculture.

The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 mg/mL. The compound 5f bearing a 2,6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking to the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron related deleterious side effects observed with existing antifungal compounds.

In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.

Suzuki cross-coupling reaction has developed one of the furthermost effectual approaches for the synthesis of biaryls or substituted aromatic moieties from aryl halides and arylboronic acids with a palladium-catalyst in the past two era’s. Herein, Pd-free layered double hydroxide containing nickel catalysts were prepared by co-precipitation method under ultrasonic irradiation and N2 atmosphere with different molar ratios of Ni: Mg: Al and coded as (1NiLDHs-Dr), (1.5NiLDHs-Dr) and (2NiLDHs-Dr). A series of reduced catalysts under 5%H2/N2 at different temperatures were coded as 1NiLDHs-R200, 1.5NiLDHs-R200 and 2NiLDHs-R200. As-synthesized 2NiLDHs-Dr was the superlative catalyst when coupling different aryl halides with different boronic acids derivatives. Deep investigation of all catalysts was done using different techniques such as inductively coupled plasma optical emission spectroscopy (ICP-OES), x-ray photoelectron spectroscopy (XPS), powder x-ray diffraction (XRD), thermogravimetric analyses (TGA), Fourier transfer infrared (FTIR), scanning electron microscope (SEM) connected with energy dispersive x-ray (EDX) and N2-physisorption at -196 ℃. The results attained verified that ɑ-Ni(OH)2 was fashioned for 2NiLDHs-Dr catalyst and the enclosure of nickel ions in the cationic sheet of layered structure were responsible for the fascinating catalytic efficacy rather than the basic nature of material. The Ni-containing LDHs catalysts encourage forthcoming studies in Pd-free catalyzed C-C coupling reactions.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

Piezoelectric nanotransducers may offer key advantages in comparison with conventional piezoelectrics, including more choices for types of mechanical input, positions of the contacts, dimensionalities and shapes. However, since piezo-semiconductive nanostructures are generally much easier to fabricate and integrate into functional systems than insulating materials, modeling becomes significantly more intricate and the effects of free charges have been considered only in a few studies. The available reports are complicated by the absence of proper nomenclature and figures of merit. Besides, some analyses are incomplete. For instance, the local piezopotential and free charges within axially strained conical piezo-semiconductive nanowires have only been systematically investigated for very low doping (1016 cm-3) and under compression. Here we give the definitions for the enhancement, depletion, base and tip piezopotentials, their characteristic lengths and both the tip-to-base and the depletion-to-enhancement piezopotential-ratios. As an example, we use these definitions for analyzing the local piezopotential and free charges in n-type ZnO truncated conical nanostructures with different doping levels (intrinsic, 1016 cm-3, 1017 cm-3) for both axial compression and traction. The definitions and concepts presented here may offer insight for designing high performance piezosemiconductive nanotransducers.

The ecological background condition of the semi-arid steppe region (SASR) is extremely fragile. It is recognized that the development of coal and electricity power is a kind of strong human interference behavior for regional landscape ecology. Landscape ecological classification (LEC) is the premise of landscape ecology research of the mining area. The current research on the SASR and grassland LEC of coal-power base is relatively less, but still remains uncertainty concerning how to stratify and classify urban mining landscapes into units of ecological significance at spatial scales appropriate for management. This study is based on hierarchy theory, scale theory, landscape process, the patch-corridor-matrix model, the network, the theory of multiple planning integration and the principle of remote sensing. According to the comprehensive principle, principles of the combining of structure and function, principle of the combining human-ominated and natural landscape, principle of emphasis, and principle of combining qualitative analysis with quantitative research of LEC in large-scale coal-power base(LSCPB). On the basis of occurrence method land classification, fully consider the ecological attributes of the land, integration pattern, processes and function theory of the landscape ecology, the LEC system of the LSCPB in the SASR has been constructed by using top-down decomposition classification method. Empirical research of the Victory and Mindong No.1 mining areas of Shenhua Group shows that the classification system constructed in this paper can meet the requirements of LEC and fully reflect the status of landscape ecology of LSCPB in SASR. This study can provide theoretical guidance for the landscape ecology of LSCPB, while also supporting a theoretical reference for the LEC research.

A series of MgAl-layered double hydroxide (MgAl-HT), the calcined form at 500^oC (MgAlO_x) and the re-hydrated one at 25^oC (MgAl-HT-RH) were synthesized. Physicochemical properties of the catalysts were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM). Surface area of the as-synthesized, calcined and re-hydrated catalysts was determined by N₂ physisorption at -196^oC. CO₂-teperature programmed desorption (CO₂-TPD) was applied to determine the basic sites of catalysts. The catalytic test reaction was carried out using benzaldehyde and their derivatives with nitromethane and their derivatives. The Henry products (1-15) were obtained in a very good yield using MgAl-HT-RH catalyst either by conventional method at 90^oC in liquid phase, or under microwave irradiation method. The mesoporous structure and basic nature of re-hydrated solid catalyst were responsible for their superior catalytic efficiency. The robust nature was determined by using the same catalyst for five times, where the product % yield was almost unchanged significantly.

Abiotic stresses, including drought, salinity, cold, heat, and heavy metals, extensively reduce global agricultural production. Approaches such as conventional breeding and transgenic breeding have been widely used to cope with these environmental stresses. The clustered regularly interspaced short palindromic repeat- Cas (CRISPR/Cas) based gene-editing tool has revolutionized due to its simplicity, accessibility, adaptability, flexibility, and wide applicability. This system has a great potential to build up crop varieties with enhanced tolerance against abiotic stresses. In this review, we summarize the most recent findings on understanding the mechanism of abiotic stress response in plants and the application of CRISPR/Cas mediated gene-editing system towards enhanced tolerance to drought, salinity, cold, heat, and heavy metals stresses. Furthermore, in this review, we highlighted the recent advancements in prime editing and base editing tools for crop improvement.

Using density functional theory (DFT) and the information-theoretic approach (ITA) quantities to appreciate the energetics and properties of biopolymers is still an unaccomplished and ongoing task. To this end, we studied the building blocks of nucleic acid base pairs and small peptides. For base pairs, we have dissected the relative importance of energetic components by using two energy partition schemes in DFT. Our results convincingly show that the exchange-correlation effect predominantly governs the molecular stability of base pairs while the electrostatic potential plays a minor but indispensable role, and the steric effect is trivial. Furthermore, we have revealed that simple density-based ITA functions are in good relationships with molecular polarizabilities for a series of 30 hydrogen-bonded base pairs and all 20 natural α-amino acids, 400 dipeptides, and 8000 tripeptides. Based on these lines, one can easily predict the molecular polarizabilities of larger peptides, even proteins as long as the total molecular wavefunction is available, rather than solving the computationally demanding coupled-perturbed Hartree-Fock (CPHF) equation or its DFT counterpart coupled-perturbed Kohn-Sham (CPKS) equation.

In the diagnosis of olfactory neuroblastoma (ONB), the presence of S-100–positive sustentacular cells surrounding the tumor is important; however, these are also present in normal nasal sinus epithelium. Although ONB often has a different final diagnosis, complete resection of the tumor has a good prognosis and minimally affects the patient's treatment plan. When the tumor extends around the internal carotid artery (ICA), complete resection is difficult due to the high risk of vascular injury; revascularization using a high-flow bypass can avoid this complication. In the present case, the tumor was located in the left sphenoid sinus and extended around the ICA. Preoperative biopsy tissue was positive for neuroendocrine markers and slightly positive for S-100 protein, leading to a diagnosis of ectopic ONB. High-flow bypass revascularization with trapping of the ICA allowed complete tumor resection. The postoperative histopathological diagnosis was neuroendocrine carcinoma, showing no S-100 protein–positive cells. There was no sign of recurrence two and a half years after surgery without additional treatment. This case demonstrates that the presence of S-100 protein–positive cells in ONB may be misleading. Although misdiagnosis of ectopic ONB should be anticipated, a complete resection of the tumor is an effective treatment strategy.

Laser shock peening as an innovative surface treatment technology can effectively improve the fatigue life, sur-face hardness, corrosion resistance, and residual compressive stress. Compared with the laser shock peening, the warm laser shock peening (WLSP) is a new surface treatment technology to improve materials’ surface performances, which takes advantage of thermal mechanical effects on stress strengthening and micro-structure strengthening, results in more stable distribution of the residual compressive stress under heating and cyclic loading process. In this paper, the microstructure of GH4169 nickel super-alloy processed by WLSP technology with differ-ent laser parameters were investigated. The proliferation and tangling of dislocations in GH4169 were observed and the dislocation density increased after WLSP treatment. The influences of different treatment by LSP and WLSP on the microhardness distribution of the surface and along cross-sectional depth were investi-gated. The microstructure evolution of the GH4169 alloy being shocked with WLSP were studied by TEM. The effect of temperature on the stability of high temperature microstructure and properties of GH4169 alloy WLP was investigated.

Through the half-unit circle area computation using the integration of the corresponding curve power series representation, we deduce a slow converging positive infinite series to $\pi$. However, by studying the remainder of that series we establish sufficiently close inequalities with equivalent lower and upper bound terms allowing us to estimate, more precisely, how the series approaches $\pi$. We use the obtained inequalities to compute up to four-digit denominator, what are in this sense, the best rational numbers that can replace $\pi$. It turns out that the well-known convergents of the continued fraction of $\pi$, $22/7$ and $355/113$ called, respectively, Yuel\"{u} and Mil\"{u} in China are the only ones found. Thus we apply a similar process to find rational estimations to $\pi+e$ where $e$ is taken as the power series of the exponential function evaluated at $1$. For rational numbers with denominators less than $2000$, the convergent $920/157$ of the continued fraction of $\pi+e$ turns out to be the only rational number of this type.

Vertical-channel organic dual-gate/base transistors would be highly interesting since vertical organic transistors are the fastest organic transistors demonstrated today. However, incorporating a dual gate/base structure into an ultra-short channel vertical architecture represents a substantial challenge. Here, we successfully realize a new device concept of vertical organic permeable dual-base transistors (OPDBTs), where either of both base electrodes can be used to change the on-currents and tune the threshold voltages. The optimized devices yield a high on-current density of 1.54 A cm^-2 and a large current gain of 9.2×10⁵, corresponding to a high transmission value of 99.998%. The detailed operation mechanisms are investigated by calibrated TCAD simulations with the Poole-Frenkel mobility model, Gaussian density of states and tunneling model. Finally, high-performance logic circuits, e.g. inverter, NAND/AND computation functions are demonstrated with one single OPDBT operating at supply voltages of < 2.0 V. We believe that OPDBTs offer a compact and technologically simple hardware platform with excellent application potential for vertical-channel organic transistors in complex logic circuits.

Background: Iranian traditional medicine is a holistic school of medicine with a long prolific history. It describes numerous concepts and the relationships between them. However, no unified terminology has been proposed for the concepts of this medicine up to the present time. Considering the extensive use of concepts in the numerous textbooks written by the scholars over centuries, comprehending the totality of the terminology is obviously a very challenging task. To resolve this issue and overcome the obstacles, and code the concepts in a reusable manner, constructing an ontology of the concepts of Iranian traditional medicine seems a necessity.Methods: Makhzan al-Advieh, an encyclopedia of materia medica compiled by Mohammad Hossein Aghili Khorasani, was selected as the resource to create an ontology of Mizaj. The steps followed to accomplish this task included (1) compiling the list of classes for Mizaj; (2) arranging the classes in taxonomy; (3) determining object properties and their cardinalities; (4) specifying annotation properties including codes, labels, synonyms, and definitions for each concept; (5) reviewing the fields pertaining to Mizaj of all monographs in Makhzan al-Advieh. The ontology was created using Protégé with adherence to the principles of ontology development provided by the Open Biological and Biomedical Ontology (OBO) foundry. Results: Mizaj ontology was constructed with a final inclusion of 105 classes, three object properties, and 1078 axioms in the Iranian Traditional Medicine General Ontology database, IrGO, freely available at http://jafarilab.com/irgo/. An indented tree view and an interactive graph view using WebVOWL were used to visualize the ontology. All classes were linked to their instances in the UNaProd database to create a knowledge-base of Mizaj. Conclusion: We constructed an ontology-based knowledge base of ITM concepts of Mizaj in the domain of materia medica to help offer a shared and common understanding of this concept, enable reuse of the knowledge, and make the assumptions explicit. Extending IrGO will bridge the gap between traditional and conventional schools of medicine and help guide future research on new treatment options.

Here we evaluate the chemistry of mineral soil solutions collected by suction lysimeters in a small mountain catchment that was affected by acidification-related spruce die-back. The aim was to obtain new insights into spatial patterns of nutrient partitioning during acidification recovery. This was achieved by comparing nutrient concentrations in soil solutions, collected along a V-shaped valley, with those in runoff. Five nests of suction lysimeters were installed in the 33-ha UDL catchment at different topographic positions (hilltops, slopes and valley). Following a 1-year equilibration, monthly samples of soil solutions were collected over a 2-year period. In the vicinity of each lysimeter nest, soil pits were excavated for a study of soil chemistry. Soil solutions were analyzed for SO42-, NO3-, DOC, NH4+, Na+, K+, Ca2+, Mg2+, and total dissolved Al concentrations, DOC and pH. For a P release estimation, ammonium oxalate extraction of soil samples was performed. Comparison of soil water data from this study with other European studies indicated that major environmentally relevant chemical species at UDL had concentrations similar to median concentrations across numerous previously acidified sites. CEC (≤ 58 meq kg-1) and BS (≤ 13 %), however, were significantly lower at UDL than at other European sites, documenting incomplete recovery from acidification. Spatial trends and seasonality in soil water chemistry support belowground inputs from mineral-stabilized legacy pollutants and soil nutrients. Seasonal variability of soil water sulfate and nitrate was significant. High nitrate in soil solutions during summer originated during the preceding dormant season, and high sulfate concentrations observed during the winter originating from recycled organic S during the summer. Higher concentrations of SO42-, NO3-, and base cations in runoff than in soil solutions may be explained by lateral surficial runoff leaching pollutants and nutrients from very shallow soil horizons. Nearly 30 years after peak acidification, solutions in mineral subsoil at UDL exhibited similar concentrations of SO42-, Ca2+ and Mg2+ as median values at the Pan-European International Co-operative Program (ICP) Forest sites, yet NO3- concentrations were an order of magnitude higher than the ICP sites. Calcium applied on soil surface by liming 32 to 11 years ago affected runoff more than soil solutions, suggesting contribution of both shallow soil water and groundwater to runoff.

Collisional mountain belts commonly develop intramontane basins from mechanical and isostatic subsidence during orogenic development. These frequently display a relict top surface, evidencing a change interval from basin infilling to erosion often via capture or overspill. Such surfaces provide markers that inform on orogenic growth patterns via climate and base level interplay. Here, we describe the top surface from the Sorbas Basin, a key intramontane basin within the Betic Cordillera (SE Spain). The surface is fragmentary comprising high elevation hilltops and discontinuous ridges developed onto the variably deformed final basin infill outcrop (Gochar Formation). We reconstruct surface configuration using DEM interpolation and apply ¹⁰Be/²⁶Al cosmonuclides to assess surface formation timing. The surface is a degraded Early Pleistocene erosional pediment developed via autogenic switching of alluvial fan streams under stable dryland climate and base level conditions. Base level lowering since the Middle Pleistocene focused headwards incision up interfan drainages, culminating in fan head capture and fan morphological preservation within the abandoned surface. Post abandonment erosion has lowered the basin surface by 31 m (average) and removed ~5.95 km³ of fill. Regional basin comparisons reveal a phase of Early Pleistocene surface formation, marking landscape stability following the most recent Pliocene-Early Pleistocene mountain building. Post-surface erosion rate quantification is low and in accordance with ¹⁰Be denudation rates typical of the low uplift Betic Cordillera.

In general, isolators and dampers used in seismically isolated buildings are designed to be isotropic in any horizontal direction. However, in the case of buildings with plan irregularities, their nonlinear responses depend on the direction of seismic loading. To discuss the influence of the angle of seismic incidence (ASI) on the nonlinear response of irregular building structures, it is important to define the angle of the critical axis of the horizontal ground motion. One possible choice is the “principal axis of ground motion” proposed by Arias (1970). However, because this principal axis is independent of the natural period of a structure, it could be complicated to use for seismically isolated structures with long natural periods. In this study, the influence of the ASI of long-period pulse-like seismic input on an irregular base-isolated building is investigated. First, the angle of the principal axis of ground motion is defined in terms of the cumulative energy input. Then, a nonlinear time-history analysis of a five-story irregular base-isolated building is performed using 10 long-period pulse-like ground motion records considering various ASIs. The results show that, compared with the principal axis of ground motion proposed by Arias, defining the principal axis of ground motion in terms of the cumulative energy input is more suitable for discussions concerning the influence of the ASI on the response of an irregular base-isolated building.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

The C5-methylation of uracil to form 5-methyluracil (m⁵U) is a ubiquitous base modification of nucleic acids. Four enzyme families have converged to catalyze this methylation using different chemical solutions. Here, we investigate the evolution of 5-methyluracil synthase families in Mollicutes, a class of bacteria that has undergone extensive genome erosion. Many mollicutes have lost some of the m⁵U methyltransferases present in their common ancestor. Cases of duplication and subsequent shift of function are also described. For example, most members of the Spiroplasma subgroup, use the ancestral tetrahydrofolate-dependent TrmFO enzyme, to catalyze the formation of m⁵U54 in tRNA, while a TrmFO paralog (termed RlmFO) is responsible for m⁵U1939 formation in 23S RNA. RlmFO has replaced the S-adenosyl-l-methionine (SAM)-enzyme RlmD that adds the same modification in the ancestor and which is still present in mollicutes from the Hominis subgroup. Another paralog of this family, the TrmFO-like protein, has a yet unidentified function that differs from the TrmFO and RlmFO homologs. Despite having evolved towards minimal genomes, the mollicutes possess a repertoire of m⁵U modifying enzymes that is highly dynamic and has undergone horizontal transfer. This emphasizes the necessity for combining bioinformatics predictions with empirical testing and structural information to get a reliable functional annotation of these enzymes.

Over the years, sustainability, impact on the environment, as well as the operation expenditure have been a major concern to the deployment of mobile cellular base stations worldwide. This is because the mobile cellular base stations are known to consume a high percentage of power within the mobile cellular network. Such energy consumption contributes to the emission of Greenhouse Gases (GHG) through the use of conventional diesel generating a set. As a result, the mobile cellular operators are faced with the dilemma of minimising the power consumption, GHG emission, and the operation cost, while improving the Quality of Service of the networks. In attempting to find a solution, this study presents the feasibility and simulation of a solar photovoltaic (PV) with battery hybrid power system (HPS) as a predominant source of power for a specific mobile cellular base station site situated in Soshanguve area of the city of Pretoria, South Africa. It also presents the technical development, showed the environmental advantage and cost benefits of using a solar PV-battery HPS to power a base station site of a 24 hrs daily load of 241.10 kWh/d and the peak load of 20.31 kW as compared to using the HPS of solar PV-diesel generating set-battery. The solar resource pattern for the city of Pretoria was collected from The National Aeronautics and Space Administration and modelled statistically. Thus, the statistical modelling done using solar radiation resource exposure characteristic patterns of Pretoria, South Africa, revealed an average annual daily solar radiation of 5.4645 Wh/m2/d and 0.605 clearness index. The simulation and the design were done using the Hybrid Optimization Model for Electric Renewables and Matlab/Simulink software. The simulation finding shows that the HPS of solar PV-battery combination has about 59.62 % saving on Net Present Cost, Levelized Cost of Energy, and 80.87% saving on Operating cost as against conventional BS powered with Gen Set-Battery.

Background: Shared value creation in Base of the Pyramid (BoP) communities is a crucial process towards building sustainable societies. BoP communities in developing countries represent more than four billion people who live on low incomes with limited access to basic products and services. Current or emerging technologies offer promising solutions for organisations pursuing manufacturing opportunities in BoP communities. This study seeks to explore the literature on how BoP communities may become active participants in sustainably manufacturing products using micro-manufacturing factories. The research question posed is: What are the core concepts that need to be taken into consideration for creating shared value through micro-manufacturing factories in BoP communities? Method: A Systematised Literature review (SLR) was completed following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) method for data selection criteria and analysis. The SLR is used to explore the state of literature with regards to creating manufacturing shared value in BoP communities with the objective to identify study gaps and to explore shared value creation concepts. Results: Literature indicates BoP initiatives that have pursued to engage BoP communities through various innovation strategies. The findings of the review is organised under three strategic pillars: Capability building strategy, Implementation process, and Growth strategy. The capability building strategy defines the users’ intention to create shared value in BoP communities with Micro-manufacturing factories (MMF). It is followed by the implementation process which guides the users to create manufacturing shared value in BoP communities. This is followed by a growth strategy to scale for impact.

Conventional plant breeding methods exploit already existing genomic variation in plants to develop a variety in 8 to 10 years, which can decrease the genetic variability of the plant’s genome. The ever-increasing food demand for cereals crops cannot be met by traditional breeding methods. In order to increase food production in less time, there is a dire need to improve breeding methods. Several conventional and molecular breeding methods are being used to improve the crops traits. Molecular researchers have developed new genome editing tools like CRISPR/Cas9, CRISPR/Cpf1, prime editing, base editing, dcas9 epigenetic modification, and several other transgene-free genomes editing approaches. These genome editing tools can improve the desired traits precisely and efficiently. Moreover, a newly developed breeding method “Speed Breeding” has revolutionized the agriculture by shortening the crop cycle. It can produce 5-6 generations of cereals in a year. In this review, we have summarized all these conventional and molecular breeding approaches to improve cereal crops.

Deployment of unmanned aerial vehicles (UAVs) as aerial base stations (ABSs) has been considered to be a feasible solution to provide network coverage in scenarios where the conventional terrestrial network is overloaded or inaccessible due to an emergency situation. This article studies the problem of optimal placement of the UAVs as ABSs to enable network connectivity to the users in a coverage free zone. The main contributions of this work include two approaches to position the UAVs and to assign user equipment (UE) to each UAV, such that the sum-rate and the coverage probability of the network is maximized. An approach can be selected depending on the prevailing scenario. The first approach uses clustering algorithm to determine the 2D positioning of the UAV and a matching algorithm is used for UE assignment by considering the characteristics of the air-to-ground propagation channels as well as the impact of co-channel interference from ABSs. Then it uses exhaustive search on different altitudes to find the optimal altitude. In the second approach, 2D positioning and UE assignment are done similarly to the first approach. However, the sub-optimal altitude is estimated using particle swarm optimization (PSO). The first approach is suitable for a system which has computational resource constraints or lower probability of line of sight (LoS) links. In contrast, the second approach is suitable for data rate greedy systems or a higher probability of LoS links.

Construction and demolition waste (CDW) represents 1/3 of the weight of all-waste produced. Increasing their recycling and reutilization with recycled aggregates (RA) means closing the life cycle of construction materials. Research has been carried out on artificial aggregates from the exclusive crushing of structural concrete waste in selective demolitions (CDWRConc). This study analyses the use of recycled concrete as graded aggregate (GARConc) and in cement soil (CSRConc). The material complies with the requirements as a road base, although due to the low values of resistance to fragmentation these materials are adequate for use in sensitive road systems and other places such as urban roads and car parks. The sensitive road systems are infrastructures in places of great natural wealth and low traffic intensity, with an annual average of heavy vehicle traffic (AADTh) below 50 vhp/d. As soluble salt contents have been detected, additional waterproofing or drainage measures must be adopted to prevent water infiltration into the layers made up of CDWRHorm. Finally, the high initial values of UCS allow the temporary passage of light vehicles over CSRConc after 3 days.

Background: Ongoing molecular profiling studies enabled by advances in biomedical technologies are producing vast amounts of ‘omic’ data for early detection, monitoring, and prognosis of diverse diseases. A major common limitation is the scarcity of biological samples, necessitating integrative modeling frameworks that can make optimal use of available data for disease classification tasks. Related data sets are often available from different studies, but may have been generated using different technology platforms. Thus, there is a critical need for flexible modeling methods that can handle data from diverse sources to facilitate the discovery of robust biomarkers that underlie disease regulatory processes. Results: In this paper, we introduce a novel framework called Knowledge Augmented Rule Learning (KARL), which incorporates two sources of knowledge, domain, and data, for pattern discovery from small and high-dimensional datasets, such as transcriptomic data. We propose KARL as a transfer rule learning framework in which knowledge of the domain is transferred to the learning process on data in order to 1) improve the reliability of the discovered patterns, and 2) study the knowledge of the domain when used along with data for modeling. In this work, we generated KARL models on gene expression datasets for five types of cancer, including brain, breast, colon, lung, and prostate. As our knowledge of the domain, we used the Ingenuity Knowledge Base (IKB) to extract genes related to hallmarks of cancer and annotated these prior relationships before learning classifiers from these datasets. Conclusions: Our results show that KARL produces, on average, rule models that are more robust classifiers than the baseline without such background knowledge, for our tasks of cancer prediction using 25 publicly available gene expression datasets. Moreover, KARL helped us learn insights about previously known relationships in these gene expression datasets, along with new relationships not input as known, to enable informed biomarker discovery for cancer prediction tasks. KARL can be applied to modeling similar data from any other domain and classification task. Future work would involve extensions to KARL to handle hierarchical knowledge to derive more general hypotheses to drive biomedicine.

Deep neural networks (DNN) have successfully delivered a cutting-edge performance in several fields. With the broader deployment of DNN models on critical applications, the security of DNNs becomes an active and yet nascent area. Attacks against DNNs can have catastrophic results, according to recent studies. Poisoning attacks, including backdoor and Trojan attacks, are one of the growing threats against DNNs. Having a wide-angle view of these evolving threats is essential to better understand the security issues. In this regard, creating a semantic model and a knowledge graph for poisoning attacks can reveal the relationships between attacks across intricate data to enhance the security knowledge landscape. In this paper, we propose a DNN Poisoning Attacks Ontology (DNNPAO) that would enhance knowledge sharing and enable further advancements in the field. To do so, we have performed a systematic review of the relevant literature to identify the current state. We collected 28,469 papers from IEEE, ScienceDirect, Web of Science, and Scopus databases, and from these papers, 712 research papers were screened in a rigorous process, and 55 poisoning attacks in DNNs were identified and classified. We extracted a taxonomy of the poisoning attacks as a scheme to develop DNNPAO. Subsequently, we used DNNPAO as a framework to create a knowledge base. Our findings open new lines of research within the field of AI security.

During the last decades, zebrafish (Danio rerio) has become one of the most important model organisms to study different physiological and biological phenomena. Research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception in this. The best-known known function of CAs is the regulation of acid-base balance. However, studies performed with zebrafish, among others, have revealed important roles for these proteins in many other physiological processes, some of which have been unpredicted in the light of the previous studies and suggestions. Examples are roles in zebrafish pigmentation as well as motor coordination. Disruption of the function of these proteins may generate even lethal outcomes. In this review, we summarize the current knowledge of CA-related studies performed in zebrafish.

The need for a relatively quick solution to the problem of providing highways with roadside service facilities necessitates the development of a series of appropriate standard projects. To increase the efficiency of these series, it is advisable to carry out the interconnection of space-planning solutions based on a particular module. Taking into account the variety of planning and landscape characteristics of the sites for the placement of objects of the mainline service, it seems advisable to choose as a module not a square or rectangular, but a triangular configuration, which allows in most cases to harmoniously block the modules. The proposed roof module in the form of a "regular" triangle facing the tetrahedron has a structural basis in the form of a single-tier rod spatial plate. The principal space-planning solutions of all four dozen objects from the approved nomenclature of the mainline service performed in the process of analyzing the possibilities show the real possibility of solving the development tasks on the basis of this system. The use of the proposed modular system makes it possible to successfully solve a number of tasks to reduce the harmful impact on the environment and effectively use renewable energy sources.

The RNA-guided endonuclease system CRISPR-Cas9 has been extensively modified since its discovery, allowing its capabilities to be extending far beyond double-stranded cleavage to high fidelity insertions, deletions, and single base edits. Such innovations have been possible due to the modular architecture of CRISPR-Cas9 and the robustness of its component parts to modifications and the fusion of new functional elements. Here, we review the broad toolkit of CRISPR-Cas9-based systems now available for diverse genome editing tasks. We provide an overview of their core molecular structure and mechanism and distil the design principles used to engineer their diverse functionalities. We end by looking beyond the biochemistry and towards the societal and ethical challenges that these CRISPR-Cas9 systems face if their transformative capabilities are to be deployed in a safe and acceptable manner.

This study proposes a 3D particle-base (discrete) multiphysics approach for modelling calcification in the aortic valve. Different stages of calcification (from mild to severe) were simulated, and their effect on the cardiac output assessed. The cardiac flow rate decreases with the level of calcification. In particular, there is a critical level of calcification below which the flow rate decreases dramatically. Mechanical stress on the membrane is also calculated. The results show that, as calcification progresses, spots of high mechanical stress appear. Firstly, they concentrate in the regions connecting two leaflets; when severe calcification is reached, then they extend to the area at the basis of the valve.

The new climate law introduces a policy of sustainable construction, the assumption of which is the reduction of CO2 by the construction industry and the use of environmentally friendly materials, such as agricultural, mineral, and recycled waste, while limiting the consumption of natural resources. The article is a literature review that analyzes selected waste materials from various sectors of the economy that can be used as additives or partial substitutes for natural resources in the production of cement and in and cement building materials, the production of which reduces CO2 emissions, producing materials with high mechanical strength and environmentally friendly.

A series of diethylamine Mannich base of asymmetrical mono-carbonyl analogs of curcumin (AMACs) were synthesized and evaluated for cytotoxic activity against Hela Cell lines. The structures of the synthesized compounds were confirmed on the basis of FTIR, ¹H-NMR, ¹³C-NMR and mass spectral data. Preliminary cytotoxic test using BSLT showed that all the synthesized compounds exhibited more potent cytotoxic activity than that of curcumin. While results of MTT assay showed that all the synthesized compounds exhibited more potent antiproliferative activity against HeLa cell lines than that of cisplatin. Compound 2b exhibited as the most potent compound of the series. Compound 2a, 2b, 2c, and 2f had IC₅₀ (µM) less than that of compound 1a, 1b, 1c and 1f indicating that the addition of diethylamine Mannich base improves the antiproliferative activity of the parent compound.

Abstract: Two novel low-dimensional molecular magnetic materials were prepared by a self-assembling of 3d- and 5d-metal complexes. These are the first neutral heterobimetallic cyanobridged compounds involving one anisotropic Mn(III) Schiff base complex and one octacyanotungstate(V) per molecular unit. A slow diffusion of the constituents’ solutions leads to a formation of the 0D crystalline complex 1 due to coordination of a water molecule to the Mn center prevents a polymer formation. A rapid mixing of reagents results in a precipitation of the microcrystalline powder of the complex 2, which on a totality of experimental data possess 1D polymeric structure. The magnetic studies have shown that antiferromagnetic exchange interactions are dominating in 1 J/k_B= -13.1(7) K, D=-3.0(1.3) K, zJ'= -0.16(20) K and g_av=2.00(1); while the presence of the significant intramolecular Mn(III)–W(V) ferromagnetic couplings through cyanide bridges is characteristic for 2 (J/k_B = 46.1(5) K g_Mn = 2.11(3), fixed g_W = 2.0). Due to the weak interchain interactions, zJ'/k_B = –0.8(2) K, compound 2 is a metamagnet with the Néel temperature of 9.5 K undergoing a spin-flip transition at 2 kOe. The slow magnetization dynamics of 2 was investigated at DС field of 0 and 2 kOe, giving the values of τ₀ 32(15) and 36(15) ps respectively, well within the range typical for SCMs. The respective ∆_τ/k_B values were 48.4(1.2) and 44.9(1.0) K.

The absolute time and relative time are defined in terms of the 4-D Euclidean space. Our universe is the 3-D x₁x₂x₃ quantized photon space which follows the absolute time simultaneity when the universe moves along the absolute time axis of ct. The length expansion of Dx = gDx₀ is derived under the condition of the absolute time (ct) simultaneity. From the similarity between this length expansion of Dx = gDx₀ and the energy increasing of E = gE₀, it is assumed that the energy is proportional to the particle size of Dx. The extension of this assumption to the 4-D Euclidean space gives the new definition that the particle energy (E) is the 4-D volume. Then, the particle mass energy is defined as E= mc² = cDtDV = gE₀. The masses of the elementary particles are originated from the 4-D warped volume of the photon space because the particle is the warped photon space with the velocity of v < c. Therefore, the Higgs boson concept in the standard model (SM) is not needed in the present 3-D quantized space model (TQSM). The scalar boson with the spin of zero, photon with the spin of 1 and graviton with the spin of 2 are the two-boson states. Therefore, the observed Higgs boson is reinterpreted as the two-boson state of the scalar boson with the spin of zero. The cosmic muon observation and twin paradox are explained by using the absolute time and relative time. The relative time is the observed time in the twin paradox and cosmic muon observation. In the twin paradox, a person who travels the long distance is more aged than a person on the earth in terms of the relative time ages because of the space and time conversion effect (STCE effect) of the moving space distance (x). But twins are in the same ages in terms of the absolute time without STCE effect. The fast-moving cosmic muon has the expanded half-life from the time expansion of the relative time. Also, the quantum entanglement and Pauli exclusion principle are explained. The quantum base of the photon space line connects two entangled particles. Two particles and quantum base system is fluctuated along the absolute time axis by the time clicking when one particle is measured. Another particle is instantly selected by the time clicking. This is called as the quantum entanglement. The photons which are the flat photon space with the constant speed of c along the space axis and absolute time axis have the 4-D photon velocity of c_eff = 2^0.5 c. Total 10-D Euclidean space including three 3-D quantized spaces and one absolute time axis is required for the electric charges (EC), lepton charges (CC) and color charges (CC) of the elementary particles. The 3-D photon space is very stiff along the absolute time (ct) axis and very soft along the space axes. The Coulomb force through the photons (2EM waves) of the space fluctuations is much stronger than the Gravitational force through the gravitons (G waves) of the time fluctuations between two electrons.

Emulsion stabilisation of base layers surfaced with chip seals often proves problematic with chips punching into the base and early distress. This can be aggravated by the use of modified binders that restricts the evaporation of moisture from pavement layers. The introduction of New-age (Nano) Modified Emulsion (NME) stabilisation has the advantage that water is chemically repelled from the stabilised layer resulting in an accelerated development of strength. A need was identified to evaluate the early life performance of selected chip seals, together with identified binders. Three different chip seal surfacings with unconventional modified binders were constructed and evaluated using Accelerated Pavement Testing (APT) with the MMLS3. The objectives of the experimental design and testing were to evaluate binder performance, early loss of chips before chip orientation at low temperatures, punching of the chips into the NME stabilised base, deformation characteristics of a Cape seal and the effect of the use of a standard normal modified binder. This paper contains details of the NME base layer, the binder and seal selection and the test results. It is shown that a cost-effective thin chip seal in combination with a suitable binder can be used on a NME stabilised base with confidence.