Engineering and environmental assessment of soilbag-based slope stabilisation for sustainable landslide mitigation in mountainous area.

Changes in land use significantly impact landslide occurrence, particularly in mountainous areas in northern Thailand, where human activities such as urbanization, deforestation, and slope modifications alter natural slope angles, increasing susceptibility to landslides. To address this issue, an appropriate method using soilbags has been widely used for slope stabilisation in northern Thailand, but their effectiveness and sustainability require assessment. This research highlights the need to evaluate the stability of the soilbag-based method. In this study, a case study was conducted in northern Thailand, focusing on an area characterised by high-risk landslide potential. This research focuses on numerical evaluation the slope stability of soilbag-reinforced structures and discusses environmental sustainability. The study includes site investigations using an unmanned aerial photogrammetric survey for slope geometry evaluation and employing the microtremor survey technique for subsurface investigation. Soil and soilbag material parameters are obtained from existing literatures. Modelling incorporates hydrological data, slope geometry, subsurface conditions, and material parameters. Afterwards, the pore-water pressure results and safety factors are analysed. Finally, the sustainability of soilbags is discussed based on the Sustainable Development Goals (SDGs). The results demonstrate that soilbags effectively mitigate pore-water pressures, improve stability, and align with several SDGs objectives. This study enhances understanding of soilbags in slope stabilisation and introduces a sustainable landslide mitigation approach for landslide-prone regions.

More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance.

Genome instability triggers cellular senescence and is a common cause of cancer. The ribosomal RNA genes (rDNA), due to their repetitive structure, form a fragile site with frequent rearrangements. To identify eukaryotic factors that connect reduced genome stability to senescence we screened 4,876 strains of a Saccharomyces cerevisiae deletion library for aberrant rDNA and found 708 genes that contribute to its upkeep. 28 mutants caused abnormalities in non-rDNA chromosomes and among them 12 mutants have abnormalities both in rDNA and in non-rDNA chromosomes. Many mutated genes have not previously been implicated with genome maintenance nor their homologues with tumorigenesis in mammals. The link between rDNA state and senescence was broken after deletion of factors related with DNA polymerase ϵ. These mutations also suppressed the short lifespan phenotype of a sir2 mutant, suggesting a model in which molecular events at the heart of the replication fork induce abnormal rDNA recombination and are responsible for the emergence of an aging signal.

Preparation of Biodegradable Oligo(lactide)s-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic.

Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA) chains attached via disulfide bonds (Dex-g-SS-OLA) that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery. In addition, we introduced galactose (Gal) residues on the nanogels, to enhance cellular uptake by receptor-mediated endocytosis, and secondary oligo-amine (tetraethylenepentamine) groups, to aid in escape from endosomes via proton sponge effects. The obtained Dex-g-SS-OLA with attached Gal residues and tetraethylenepentamine (EI4) groups, EI4/Gal-Dex-g-SS-OLA, formed a nanogel with a hydrodynamic diameter of ca. 203 nm in phosphate-buffered solution. The collapse of the EI4/Gal-Dex-g-SS-OLA nanogels under reductive conditions was confirmed by a decrease in the hydrodynamic diameter in the presence of reductive agents. The specific uptake of the hydrogels into HepG2 cells and their intercellular behavior were investigated by flow cytometry and confocal laser scanning microscopy using fluorescence dye-labeled nanogels. Escape from the endosome and subsequent collapse in the cytosol of the EI4/Gal-Dex-g-SS-OLA were observed. These biodegradable nanogels that collapse under reductive conditions in the cytosol should have great potential as efficient drug carriers in, for example, cancer chemotherapy.

Embrittlement Fracture Behavior and Mechanical Properties in Heat-Affected Zone of Welded Maraging Steel.

In welded maraging steels, mechanical properties, particularly ductility and toughness, are often compromised in the heat-affected zone (HAZ). This study focuses on 300-grade maraging steel bars, solution annealed at 1123 K for 1.5 h (5.4 ks) and welded using gas tungsten arc welding, followed by a post-weld heat treatment at 753 K for 13.33 h (48 ks). In situ observations during three-point bending tests on HAZ samples featuring coarsened prior austenite grain sizes were conducted to examine damage behavior and the crack path near the crack tip. The main crack initiated at the peak applied load during the bending test and, upon further loading, exhibited significant deflection and extension accompanied by numerous microcracks and localized crack branching. Distinctive damage features, such as transgranular cracking across block regions, intense intergranular cracking along packet boundaries with a pronounced shear component, and crowding of microcracks ahead of the crack tip, were observed in the HAZ sample during the in situ test. The interaction between the main crack tip and microcracks and its influence on the local crack propagation driving force was discussed using fracture mechanics. Experimental results, including tensile fracture surface observations and in situ images, along with analysis of the stress anti-shielding effect by microcracks, suggest that the HAZ sample exhibits embrittlement fracture behavior with lower ductility and toughness compared to the base metal sample.

Effect of the axial ligand on the reactivity of the oxoiron(IV) porphyrin π-cation radical complex: higher stabilization of the product state relative to the reactant state.

The proximal heme axial ligand plays an important role in tuning the reactivity of oxoiron(IV) porphyrin π-cation radical species (compound I) in enzymatic and catalytic oxygenation reactions. To reveal the essence of the axial ligand effect on the reactivity, we investigated it from a thermodynamic viewpoint. Compound I model complexes, (TMP(+•))Fe(IV)O(L) (where TMP is 5,10,15,20-tetramesitylporphyrin and TMP(+•) is its π-cation radical), can be provided with altered reactivity by changing the identity of the axial ligand, but the reactivity is not correlated with spectroscopic data (ν(Fe═O), redox potential, and so on) of (TMP(+•))Fe(IV)O(L). Surprisingly, a clear correlation was found between the reactivity of (TMP(+•))Fe(IV)O(L) and the Fe(II)/Fe(III) redox potential of (TMP)Fe(III)L, the final reaction product. This suggests that the thermodynamic stability of (TMP)Fe(III)L is involved in the mechanism of the axial ligand effect. Axial ligand-exchange experiments and theoretical calculations demonstrate a linear free-energy relationship, in which the axial ligand modulates the reaction free energy by changing the thermodynamic stability of (TMP)Fe(III)(L) to a greater extent than (TMP(+•))Fe(IV)O(L). The linear free energy relationship could be found for a wide range of anionic axial ligands and for various types of reactions, such as epoxidation, demethylation, and hydrogen abstraction reactions. The essence of the axial ligand effect is neither the electron donor ability of the axial ligand nor the electron affinity of compound I, but the binding ability of the axial ligand (the stabilization by the axial ligand). An axial ligand that binds more strongly makes (TMP)Fe(III)(L) more stable and (TMP(+•))Fe(IV)O(L) more reactive. All results indicate that the axial ligand controls the reactivity of compound I (the stability of the transition state) by the stability of the ground state of the final reaction product and not by compound I itself.

Tensile Examination and Strength Evaluation of Latewood in Japanese Cedar.

With the crisis awareness of global warming and natural disasters, utilization of local wood has drawn increasing attention in achieving the Sustainable Development Goals (SDGs). It is necessary to investigate the deformation and fracture of the structural tissue in wood in order to improve the safety and reliability of wood application. However, deformation and fracture mechanisms of the structural tissue in each annual ring are unknown. The mechanical characteristics of wood are reflected in the properties of earlywood and latewood. In the present study, microstructural observation and tensile tests were conducted to examine the relationship between the mechanical properties and fracture behavior of latewood in the growth direction in Japanese cedar. Brittle fracture behavior of the latewood specimen was confirmed based on the tensile stress-strain curve and features of the fracture surface. Moreover, two fracture modes, tensile fracture and shear fracture, were recognized. Weibull analysis of tensile strength in each fracture mode was performed to evaluate the reliability and utility of brittle latewood. Lastly, two fracture mechanisms were discussed based on the failure observation findings by a scanning electron microscope.

Cerebrospinal fluid hypovolemia syndrome mimicking ocular myasthenia gravis: A case report.

Purpose: Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage. The aim of this study is to report a rare case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with fluctuation and was initially diagnosed with ocular myasthenia gravis. Observeations: A 29-year-old man exhibited fluctuating left ptosis and diplopia after a traffic accident. Although he was suspected of having myasthenia gravis and was treated using oral pyridostigmine bromide, his symptoms did not improve. He also had orthostatic headaches and malaise after the accident. His symptoms were suspected to be associated with traumatic cerebrospinal fluid hypovolemia. After 1000-mL fluid replacement, his diplopia and ptosis improved, and orbital T2-weghted MRI detected a high-signal zone around the optic nerve. We diagnosed him with oculomotor nerve paresis associated with cerebrospinal fluid hypovolemia. The symptoms, including ptosis, diplopia, orthostatic headaches, and malaise, disappeared after epidural blood patch therapy. Conclusions and Importance: When treating patients with fluctuating ocular symptoms, such as diplopia and ptosis, who have a history of trauma and orthostatic headaches, the possibility of CHS should be considered in the differential diagnosis.

Optic nerve-associated connective tissue structures revisited: A histological study using human fetuses and adult cadavers.

Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve fibers into fascicles. We collected specimens from 25 adult cadavers and 15 fetuses and revisited the histological architecture of the optic and oculomotor nerves. In the optic chiasma, the meningeal layer of the dura joins the pia to form a thick SPM, and the periosteum of the sphenoid is continuous with the dural sheath at the orbital exit of the bony optic canal. The septa appeared as a cluster of irregularly arrayed fibrous plates in the intracranial course near the chiasma. Thus, the septa were not derived from either the SPM or the dural sheath. In the orbit, the central artery of the retina accompanies collagenous fibers from the dural sheath and the SPM to provide the vascular sheath in the optic nerve. These connective tissue configurations were the same between adult and fetal specimens. At the optic disk, the dural sheath and SPM merged with the sclera, whereas the septa appeared to end at the lamina cribrosa. However, in fetuses without lamina cribrosa, the septa extend into the nerve fiber layer of the retina. The SPM and septa showed strong elastin immunoreactivity, in contrast to the absence of reactivity in the sheaths of the oculomotor nerve. Each S100 protein-positive Schwann sheath of the oculomotor nerve was surrounded by collagenous endoneurium. Glial fibrillary acidic protein-positive astrocytes showed a linear arrangement along the septa.

Time-series transcriptome of Brachypodium distachyon during bacterial flagellin-induced pattern-triggered immunity.

Plants protect themselves from microorganisms by inducing pattern-triggered immunity (PTI) via recognizing microbe-associated molecular patterns (MAMPs), conserved across many microbes. Although the MAMP perception mechanism and initial events during PTI have been well-characterized, knowledge of the transcriptomic changes in plants, especially monocots, is limited during the intermediate and terminal stages of PTI. Here, we report a time-series high-resolution RNA-sequencing (RNA-seq) analysis during PTI in the leaf disks of Brachypodium distachyon. We identified 6,039 differentially expressed genes (DEGs) in leaves sampled at 0, 0.5, 1, 3, 6, and 12 hours after treatment (hat) with the bacterial flagellin peptide flg22. The k-means clustering method classified these DEGs into 10 clusters (6 upregulated and 4 downregulated). Based on the results, we selected 10 PTI marker genes in B. distachyon. Gene ontology (GO) analysis suggested a tradeoff between defense responses and photosynthesis during PTI. The data indicated the recovery of photosynthesis started at least at 12 hat. Over-representation analysis of transcription factor genes and cis-regulatory elements in DEG promoters implied the contribution of 12 WRKY transcription factors in plant defense at the early stage of PTI induction.

Add-on imeglimin versus metformin dose escalation regarding glycemic control in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor plus low-dose metformin: study protocol for a multicenter, prospective, randomized, open-label, parallel-group comparison study (MEGMI study).

INTRODUCTION: Imeglimin is a novel anti-hyperglycemic drug that improves both insulin resistance and insulin secretion. The effects of imeglimin on glycemic control were confirmed in phase III clinical trials, but little is known about its effectiveness in daily clinical practice settings, especially compared with metformin. Therefore, we aim to clarify the efficacy of imeglimin in patients with type 2 diabetes (T2D) being treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor plus low-dose metformin. RESEARCH DESIGN AND METHODS: This is a multicenter, randomized, prospective, open-label, parallel-group trial. Seventy participants with T2D treated with a DPP-4 inhibitor plus metformin (500-1000 mg/day) for more than 12 weeks and a glycated hemoglobin (HbA1c) level of 52-85 mmol/mol (7.0%-9.9%) will be randomized to receive add-on imeglimin 1000 mg two times per day or metformin dose escalation for 24 weeks. Biochemical analyses and physical assessments will be performed at baseline and at the end of the study, and adverse events will be recorded. The primary endpoint is the change in HbA1c after 24 weeks. The secondary endpoints comprise the changes in blood pressure, pulse rate, body weight, abdominal circumference, and other laboratory parameters; the relationship between improvements of biological parameters including glycemic control and patient background characteristics; and side effects. RESULTS: This study will reveal new insights into the incorporation of imeglimin into the diabetes treatment strategy. CONCLUSIONS: This will be the first randomized controlled trial to compare the efficacy of adding imeglimin versus metformin dose escalation on glycemic control in patients with T2D. TRIAL REGISTRATION NUMBER: jRCT1011220005.

Redox potentials of oxoiron(IV) porphyrin π-cation radical complexes: participation of electron transfer process in oxygenation reactions.

The oxoiron(IV) porphyrin π-cation radical complex (compound I) has been identified as the key reactive intermediate of several heme enzymes and synthetic heme complexes. The redox properties of this reactive species are not yet well understood. Here, we report the results of a systematic study of the electrochemistry of oxoiron(IV) porphyrin π-cation radical complexes with various porphyrin structures and axial ligands in organic solvents at low temperatures. The cyclic voltammogram of (TMP)Fe(IV)O, (TMP = 5,10,15,20-tetramesitylporphyrinate), exhibits two quasi-reversible redox waves at E(1/2) = 0.88 and 1.18 V vs SCE in dichloromethane at -60 °C. Absorption spectral measurements for electrochemical oxidation at controlled potential clearly indicated that the first redox wave results from the (TMP)Fe(IV)O/[(TMP(+•))Fe(IV)O](+) couple. The redox potential for the (TMP)Fe(IV)O/[(TMP(+•))Fe(IV)O](+) couple undergoes a positive shift upon coordination of an anionic axial ligand but a negative shift upon coordination of a neutral axial ligand (imidazole). The negative shifts of the redox potential for the imidazole complexes are contrary to their high oxygenation activity. On the other hand, the electron-withdrawing effect of the meso-substituent shifts the redox potential in a positive direction. Comparison of the measured redox potentials and reaction rate constants for epoxidation of cyclooctene and demethylation of N,N-dimethylanilines enable us to discuss the details of the electron transfer process from substrates to the oxoiron(IV) porphyrin π-cation radical complex in the oxygenation mechanisms.

Quartz-crystal scanning probe microcantilevers with a silicon tip based on direct bonding of silicon and quartz.

This paper reports on the design, fabrication and characterization of cantilever-shaped quartz-crystal resonators for scanning probe microscopy (SPM) in order to operate under various environments, especially in liquids for biological applications. The cantilevers have functions of self-sensing and self-actuation using piezoelectric effects, and these properties are demonstrated experimentally. Compared to conventional SPM cantilevers, this quartz cantilever is easy to utilize as a SPM based force sensor in liquids because the self-actuating properties can lead to no spurious resonant peaks. In addition, the self-sensing properties will enable its use even in an opaque liquid and can simplify the SPM system. In this research, quartz cantilevers are fabricated on silicon using a silicon-quartz direct bonding technique, and the sharp silicon tip is integrated at the end of the cantilever as well. Additionally, the electrical Q-enhancement (active Q-control) was tested.

Cerebrospinal fluid hypovolemia syndrome after a traffic accident with abnormal eye movements: A case report.

PURPOSE: To describe a rare case of cerebrospinal fluid hypovolemia syndrome after a traffic accident with abnormal eye movements. OBSERVATIONS: A 19-year-old man was referred to our clinic after being hit by a car five months ago while riding a bicycle. After the accident, he sometimes noticed oscillopsia, and had postural headaches and reading difficulties. His eye movement recording revealed square wave jerks during fixation and decreased pursuit gain during horizontal smooth pursuit. MR myelography detected cerebrospinal fluid leakage and the patient was diagnosed with cerebrospinal fluid hypovolemia. After undergoing epidural blood patch therapy, the leakage disappeared, and his postural headaches improved immediately. Square wave jerks and decreased pursuit gain improved, and his oscillopsia and reading difficulty also improved after therapy. CONCLUSIONS AND IMPORTANCE: A patient with cerebrospinal fluid hypovolemia presented with square wave jerks and decreased pursuit gain. Epidural blood patch therapy was effective for the symptoms. When treating patients with oscillopsia and postural headaches, we should consider the possibility of cerebrospinal fluid hypovolemia syndrome in the differential diagnosis.

QTL mapping using microsatellite linkage reveals target-site mutations associated with high levels of resistance against three mitochondrial complex II inhibitors in Tetranychus urticae.

The acaricides cyflumetofen, cyenopyrafen, and pyflubumide act as inhibitors of the mitochondrial electron transport system at complex II (succinate dehydrogenase; SDH), a new mode of action in arthropods. The development and mechanisms of low-level resistance against cyenopyrafen and cyflumetofen have been previously reported in Tetranychus urticae. In the present study, we investigated high levels of resistance against three SDH inhibitors in T. urticae field populations and clarify the genetic basis of resistance using quantitative trait locus (QTL) analysis. First, we constructed a microsatellite linkage map comprising 64 markers assembled into three linkage groups (LGs) with total length of 683.8 cM and average marker spacing of 11.03 cM. We then used the linkage map to perform QTL mapping, and identified significant QTLs contributing to resistance to cyflumetofen (one QTL on LG1), cyenopyrafen (one QTL on LG3), and pyflubumide (two QTLs on LG1 and LG3). The QTL peaks on LG1 for cyflumetofen and pyflubumide overlapped and included the SdhB locus. For cyenopyrafen resistance, the QTLs on LG3 included the SdhC locus. For cyflumetofen resistance, we found an I260T mutation in SdhB. For pyflubumide and cyenopyrafen resistance, we detected I260V and S56L substitutions in SdhB and SdhC, respectively, by direct sequencing. Both I260 in SdhB and S56 in SdhC were present in highly conserved regions of the ubiquinone binding site formed at the interface among SdhB, SdhC, and SdhD. Mutations at these positions have been implicated in resistance against fungicides that act as Sdh inhibitors in various pathogens. Therefore, we consider these mutations to be target-site resistance mutations for these acaricidal SDH inhibitors.

Effect of imidazole and phenolate axial ligands on the electronic structure and reactivity of oxoiron(IV) porphyrin pi-cation radical complexes: drastic increase in oxo-transfer and hydrogen abstraction reactivities.

To study the effect of axial ligands on the electronic structure and reactivity of compound I of peroxidases and catalases, oxoiron(IV) porphyrin pi-cation radical complexes with imidazole, 2-methylimidazole, 4(5)-methylimidazole, and 3-fluoro-4-nitrophenolate as the axial ligands were prepared by ozone oxidation of iron(III) complexes of 5,10,15,20-tetramesitylporphyrin (TMP) and 2,7,12,17-tetramethyl-3,8,13,18-tetramesitylporphyrin (TMTMP). These complexes were fully characterized by absorption, (1)H, (2)H, and (19)F NMR, electron paramagnetic resonance (EPR), and electrospray ionization mass spectrometry (ESI-MS) spectroscopy. The characteristic absorption peak of compound I at approximately 650 nm was found to be a good marker for estimation of the electron donor effect from the axial ligand. The axial ligand effect did not change the porphyrin pi-cation radical state, the a(2u) state of the TMP complexes, or the a(1u) radical state of both the TMTMP complexes and compound I. The ferryl iron and porphyrin pi-cation radical spins were effectively transferred into the axial ligands for the a(2u) complexes but not for the a(1u) complexes. Most importantly, the reactivity of the oxoiron(IV) porphyrin pi-cation radical complex was drastically increased by the imidazole and phenolate axial ligands. The reaction rate for cyclooctene epoxidation was increased 100- to 400-fold with axial coordination of imidazoles and phenolate. A similar increase was also observed for the oxidation of 1,4-cyclohexadiene,N,N-dimethyl-p-nitroaniline and hydrogen peroxide. These results suggest extreme enhancement of the reactivity of compound I by the axial ligand in heme enzymes. The functional role of axial ligands on the compound I in heme enzymes is discussed.

Prevention of stroke and dementia by statin therapy: experimental and clinical evidence of their pleiotropic effects.

Stroke and dementia are major causes of disability in most countries. Epidemiological studies have demonstrated that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are likely to reduce the risk for developing these formidable disorders. The favorable outcomes in statin users may be attributable to not only cholesterol-dependent actions, but also various cholesterol-independent actions called "pleiotropic effects." Several clinical trials have suggested that statins decrease the incidence of stroke, especially ischemic stroke. Statins improve endothelial function, inhibit platelet activation, reduce blood coagulability, and suppress inflammatory reactions, all of which may contribute to the beneficial effects of the therapy. Statins also reduce the risk of vasospasm caused by subarachnoid hemorrhage (SAH). In addition, statins might inhibit the development and progression of Alzheimer's disease (AD), the dominant type of dementia in most industrialized countries, upstream of the amyloid cascade. In vitro studies have shown that statins modulate the metabolism of the beta-amyloid precursor protein (APP) and reduce the extracellular level of its proteolytic product, amyloid-beta (Abeta). The aggregated Abeta is cytotoxic, leading to formation of neurofibrillary tangles and neuronal loss in the brain. Inflammatory processes are active in AD and may contribute significantly to AD pathology. We review the experimental background regarding the pleiotropic effects of statins and summarize clinical trials that examined the preventative effects of statin therapy on stroke and dementia. We include current trials in which statin therapy is initiated within 24 hr of onset of acute ischemic stroke.

Efficacy of Vonoprazan for Gastroesophageal Reflux Symptoms in Patients with Proton Pump Inhibitor-resistant Non-erosive Reflux Disease.

Objective Clinically, patients with proton pomp inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD) are very challenging to treat. The aim of this study was to determine the rates of symptom relief and adverse events among PPI-resistant GERD patients that changed their therapy from a PPI to vonoprazan. Methods Patients with severe gastroesophageal reflux symptoms (total GERD-Q score ≥8) without endoscopic findings of mucosal breaks who changed their medication from a PPI to vonoprazan during a 12-week period from 2015 to 2016 at 2 hospitals were selected. The primary outcome was the self-reported relief of gastroesophageal reflux symptoms. The odds ratio (OR) for the improvement of symptoms was calculated based on an exact binomial distribution using a matched-pair analysis. The secondary outcome was the GERD-Q score and adverse events. Results Twenty-six patients (6 men) with a mean age of 67.5 years were analyzed. After the therapy was changed from a PPI to vonoprazan, 18 patients (69.2%) reported an improvement, 6 (23.1%) reported no change, and 2 (7.7%) reported an exacerbation of symptoms. A change in therapy was significantly associated with improved self-reported symptoms (OR 9.0, p<0.001). The mean total GERD-Q score during vonoprazan treatment was significantly lower than that during PPI therapy (11.96 vs. 8.92). There were no significant differences in the incidence of adverse events between the therapies. Conclusion Changing the medication from a PPI to vonoprazan was significantly associated with an improvement in gastroesophageal reflux symptoms. Vonoprazan is one of the most promising treatment options for patients with PPI-resistant GERD.