Physics-informed deep learning approach for modeling crustal deformation.

The movement and deformation of the Earth's crust and upper mantle provide critical insights into the evolution of earthquake processes and future earthquake potentials. Crustal deformation can be modeled by dislocation models that represent earthquake faults in the crust as defects in a continuum medium. In this study, we propose a physics-informed deep learning approach to model crustal deformation due to earthquakes. Neural networks can represent continuous displacement fields in arbitrary geometrical structures and mechanical properties of rocks by incorporating governing equations and boundary conditions into a loss function. The polar coordinate system is introduced to accurately model the displacement discontinuity on a fault as a boundary condition. We illustrate the validity and usefulness of this approach through example problems with strike-slip faults. This approach has a potential advantage over conventional approaches in that it could be straightforwardly extended to high dimensional, anelastic, nonlinear, and inverse problems.

Endovascular coil embolization of proximal middle cerebral artery aneurysms has better outcomes than other middle cerebral artery aneurysms: A retrospective study.

PURPOSE: Although some authors proposed that coil embolization in middle cerebral artery (MCA) aneurysms is a useful and effective alternative, the characteristics of the aneurysms may be different at each location. We compared the results of coil embolization of proximal middle cerebral artery aneurysms with those of other middle cerebral artery aneurysms. METHODS: Data from 46 patients with 50 aneurysms were retrospectively evaluated. We defined the aneurysms inside of the insular cortex as proximal MCA (pMCA) aneurysms and those outside of the insular cortex as non-proximal MCA (npMCA) aneurysms. The results of the occlusion were divided into classes 1, 2, and 3 of the Raymond scale. We collected the results of the occlusion from the operative notes supplied by a neuroendovascular specialist. RESULTS: Univariate analysis identified favorable results for pMCA aneurysms (class 1: pMCA = 22 npMCA = 11; P < 0.01). In the radiological follow-up results, we achieved class 1 in 29 patients (69%; pMCA = 21 and npMCA = 8; P < 0.01). Side wall type aneurysms (pMCA = 14, npMCA = 2; P < 0.01) and the number of branches from the neck of ≤1 (pMCA = 14, npMCA = 2; P < 0.01) were significantly recognized at the pMCA. CONCLUSIONS: Proximal middle cerebral artery aneurysm clipping is difficult because the origin of the lenticulostriate arteries is often hidden behind the aneurysmal dome. In the present study, endovascular coil embolization for pMCA aneurysms obtained better results than that for npMCA aneurysms because of the morphological characteristics. Endovascular coil embolization seems to be efficacious for pMCA aneurysms as compared with npMCA aneurysms.

Flow-Diverter Stent for an Unruptured Aneurysm at the Junction of the Internal Carotid Artery and Persistent Primitive Trigeminal Artery: Case Report and Literature Review.

BACKGROUND: Persistent primitive trigeminal artery (PPTA), which is a fetal carotid-basilar anastomosis, is the most common embryologic vascular remnant persisting in adults. Aneurysms can arise between the internal carotid artery (ICA) and PPTA. Here we present a case of ICA-PPTA aneurysm treated with a flow-diverter stent. CASE DESCRIPTION: A 52-year-old woman had left abducens nerve palsy. Imaging detected a large left ICA-PPTA aneurysm, which we chose to treat with a flow-diverter stent after embolizing the PPTA with a coil. Although the abducens nerve palsy did not change, there were no signs of cerebral infarction, and no new symptoms appeared postoperatively. Blood flow in the aneurysm had disappeared on digital subtraction angiography after 6 months. CONCLUSIONS: This is the first case report of ICA-PPTA aneurysm successfully treated with a flow-diverter stent. We could stop blood flow from the posterior circulation by embolizing the PPTA with a coil, allowing the use of a flow-diverter stent. This report can be used as a reference for the procedure in future work.

Asthenosphere rheology inferred from observations of the 2012 Indian Ocean earthquake.

The concept of a weak asthenospheric layer underlying Earth's mobile tectonic plates is fundamental to our understanding of mantle convection and plate tectonics. However, little is known about the mechanical properties of the asthenosphere (the part of the upper mantle below the lithosphere) underlying the oceanic crust, which covers about 60 per cent of Earth's surface. Great earthquakes cause large coseismic crustal deformation in areas hundreds of kilometres away from and below the rupture area. Subsequent relaxation of the earthquake-induced stresses in the viscoelastic upper mantle leads to prolonged postseismic crustal deformation that may last several decades and can be recorded with geodetic methods. The observed postseismic deformation helps us to understand the rheological properties of the upper mantle, but so far such measurements have been limited to continental-plate boundary zones. Here we consider the postseismic deformation of the very large (moment magnitude 8.6) 2012 Indian Ocean earthquake to provide by far the most direct constraint on the structure of oceanic mantle rheology. In the first three years after the Indian Ocean earthquake, 37 continuous Global Navigation Satellite Systems stations in the region underwent horizontal northeastward displacements of up to 17 centimetres in a direction similar to that of the coseismic offsets. However, a few stations close to the rupture area that had experienced subsidence of up to about 4 centimetres during the earthquake rose by nearly 7 centimetres after the earthquake. Our three-dimensional viscoelastic finite-element models of the post-earthquake deformation show that a thin (30-200 kilometres), low-viscosity (having a steady-state Maxwell viscosity of (0.5-10) × 1018 pascal seconds) asthenospheric layer beneath the elastic oceanic lithosphere is required to produce the observed postseismic uplift.

Angiopoietin-2 expression in patients with an acute exacerbation of idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: We hypothesized that increased pulmonary vascular permeability may play a role in the pathogenesis of an acute exacerbation of the idiopathic interstitial pneumonias (AE-IIPs). Angiopoietin-2 (Ang-2) promotes endothelial activation, destabilization, and inflammation. The purpose of this study was to examine whether Ang-2 expression was associated with the pathogenesis of AE-IIPs. METHODS: Twenty-three patients with AE-IIP patients, 18 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, 37 idiopathic pulmonary fibrosis (IPF) patients, and 33 healthy volunteers (HVs) were enrolled. The serum level of Ang-2 was measured by an enzyme-linked immunosorbent assay. RESULTS: The serum levels of Ang-2 were higher in AE-IIPs and ALI/ARDS patients than in IPF patients and HVs; the BALF levels of Ang-2 were also higher than in IPF patients. There was a positive correlation between the serum level of Ang-2 and the CRP in patients with AE-IIP patients, whereas a significant positive correlation was found between the serum Ang-2 level and the CRP or SOFA scores of the ALI/ARDS patients. Although the baseline Ang-2 level was not related to survival, the Ang-2 levels significantly declined in survivors during treatment, while they did not change in non-survivors. CONCLUSIONS: Increased pulmonary vascular permeability and inflammation due to Ang-2 may play a role in the pathogenesis of AE-IIPs.

Confined Singlet Oxygen in Mesoporous Silica Nanoparticles: Selective Photochemical Oxidation of Small Molecules in Living Cells.

Chemical conversion of specific bioactive molecules by external stimuli in living cells is a powerful noninvasive tool for clarification of biomolecular interactions and to control cellular functions. However, in chaotic biological environments, it has been difficult to induce arbitrary photochemical reactions on specific molecules because of their poor molecular selectivity. Here we report a selective and nontoxic photochemical reaction system utilizing photoactivated mesoporous silica nanoparticles to control biological functions. Methylene blue modification within nanoparticle pores for photosensitization produced singlet oxygen confined to the pore that could mediate selective oxidation of small molecules without any damage to living cells. This intracellular photochemical system produced bioactive molecules in situ and remotely controlled the cell cycle phase. We also confirmed that this photoreaction could be applied to control cell cycle phase in tumor tissue transplanted in mice. The cell cycle phase in the cells in mice, to which our system was administered, was arrested at the G2/M phase upon photoirradiation. We demonstrate a simple and promising method for the exogenous conversion of an intracellular biomolecule to another functional compound.

3D-FIESTA Magnetic Resonance Angiography Fusion Imaging of Distal Segment of Occluded Middle Cerebral Artery.

Middle cerebral artery (MCA) occlusion was examined with basi-parallel anatomical scanning (BPAS) using three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA), and 3D-FIESTA and magnetic resonance angiography (MRA) fusion images were created. We expected that an incidence of hemorrhagic complications due to vessel perforations would be decreased by obtaining vascular information beyond the occlusion and thus acute endovascular revascularization could be performed using such techniques. We performed revascularization for acute MCA occlusion for five patients who were admitted in our hospital from October 2012 to October 2014. Patients consisted of 1 man and 4 women with a mean age of 76.2 years (range: 59-86 years). Fusion images were created from three-dimensional time of flight (3D-TOF) MRA and 3D-FIESTA with phase cycling (3D-FIESTA-C). Then thrombectomy was performed in all the 5 patients. Merci retriever to 1 patient, Penumbra system to 1, urokinase infusion to 2, and Solitaire to 1 using such techniques. In all cases, a 3D-FIESTA-MRA fusion imaging could depict approximately clear vascular information to at least the M3 segment beyond the occlusion. And each acute revascularization was able to perform smoothly using these imaging techniques. In all cases, there was no symptomatic hemorrhagic complication. It showed that 3D-FIESTA MRA fusion imaging technique could obtain vascular information beyond the MCA occlusion. In this study, no symptomatic hemorrhagic complications were detected. It could imply that such techniques were useful not only to improve treatment efficiency but also to reduce the risk of development of hemorrhagic complications caused by vessel perforations in acute revascularization.

Controlling Localization and Excretion of Nanoparticles by Click Modification of the Surface Chemical Structures inside Living Cells.

Invited for this month's cover is the group of Drs. Takeo Ito and Kazuhito Tanabe from Kyoto University, Japan. The cover image shows accumulation of silica nanoparticles on the plasma membrane by click modification of the surface in living cells. Read the full text of the article at 10.1002/cplu.201402436.

Controlling Localization and Excretion of Nanoparticles by Click Modification of the Surface Chemical Structures inside Living Cells.

Surface modification of silica nanoparticles (SiNPs) inside living cells was conducted by using the copper-free bioorthogonal click reaction to evaluate the effects of surface chemical structures on dynamic behavior and excretion of SiNPs. The results demonstrated the spatial translocation of intracellular SiNPs to the plasma membrane upon surface modification in situ with phospholipids. Moreover, the extent and kinetics of excretion of the SiNPs from inside the cell were enhanced by modification.

Phosphorescent ruthenium complexes with a nitroimidazole unit that image oxygen fluctuation in tumor tissue.

Understanding oxygen fluctuation in a cancerous tumor is important for effective treatment, especially during radiotherapy. In this paper, ruthenium complexes bearing a nitroimidazole group are shown to report the oxygen status in tumor tissue directly. The nitroimidazole group was known to be accumulated in hypoxic tumor tissues. On the other hand, the ruthenium complex showed strong phosphorescence around 600 nm. The emission of ruthenium is quenched instantaneously by molecular oxygen due to energy transfer between triplet states of oxygen and ruthenium complex, but the emission is then recovered by the removal of oxygen. Thus, we could observe oxygen fluctuation in tumor tissue in a real-time manner by monitoring the phosphorescence of the ruthenium complex. The versatility of the probe is demonstrated by monitoring oxygen fluctuation in living cells and tumor tissue planted in mice. The ruthenium complex promptly penetrated plasma membrane and accumulated in cells to emit its oxygen-dependent phosphorescence. In vivo experiments revealed that the oxygen level in tumor tissue seems to fluctuate at the sub-minute timescale.

Hypoxic X-irradiation as an external stimulus for conformational change of oligodeoxynucleotides that possess disulfide bond and regulation of DNAzyme function.

We achieved a conformational change of oligodeoxynucleotides and the regulation of DNAzyme function by means of a radiolytic strand exchange reaction of disulfide bond. We designed a system in which the DNAzyme function of RNA cleavage was suppressed by the hybridization of an inhibitor strand that possessed disulfide bond with an active DNAzyme. Hypoxic X-irradiation led to the recovery of RNA cleavage because the strand exchange reaction at the disulfide bond in inhibitor strand resulted in a release of inhibitor strand. This strategy may be applicable to gene regulation by hypoxic X-irradiation.

Synthesis and identification of α-cyano bis(indolyl)chalcones as novel anticancer agents.

Microwave-assisted synthesis of 23 α-cyano bis(indolyl)chalcones (6a-w) and their in vitro anticancer activity against three human cancer cell lines have been discussed. Among the synthesized chalcones, compound 6n was found to be the most potent and selective against A549 lung cancer cell line (IC50 = 0.8 µM). In a preliminary mechanism of action studies some α-cyano bis(indolyl)chalcones were found to enhance tubulin polymerization suggesting these compounds could act as microtubule stabilizing agents.

A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for completely resected high-grade pulmonary neuroendocrine carcinoma (large cell neuroendocrine carcinoma and small cell lung cancer).

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high-grade neuroendocrine carcinomas (HGNEC) of the lung. In patients with completely resected HGNEC, platinum-based adjuvant chemotherapy may be considered. However, the optimum chemotherapy regimen has not been determined. We conducted a multicenter single-arm phase II trial to evaluate irinotecan and cisplatin in postoperative adjuvant chemotherapy for HGNEC patients. PATIENTS AND METHODS: Patients with completely resected stage I-IIIA HGNEC received four cycles of irinotecan (60 mg/m(2), day 1, 8, 15) plus cisplatin (60 mg/m(2), day 1). This regimen was repeated every 4 weeks. The primary endpoint was the rate of completion of chemotherapy (defined as having undergone three or four cycles), and secondary endpoints were the rate of 3-year relapse-free survival (RFS), rate of 3-year survival and toxicities. RESULTS: Forty patients were enrolled between September 2007 and April 2010. Patients' characteristics were: median age (range) 65 [45-73] years; male 85%; ECOG-PS 1 60%; LCNEC 57% and SCLC 43%; stage IA/IB/IIB/IIIA 32/35/8/5%; 95% received lobectomy. The rate of completion of chemotherapy was 83% (90%C.I.; 71-90%). The rate of overall survival at 3 years was estimated at 81%, and that of RFS at 3 years was 74%. The rates of overall survival and RFS at 3 years were 86 and 74% among 23 LCNEC patients, and 74 and 76% among 17 SCLC patients, respectively. Nineteen patients (48%) experienced grade 3 or 4 neutropenia, but only five patients (13%) developed febrile neutropenia. Two patients (5%) developed grade 3 diarrhea, and four patients (10%) had grade 3 nausea. No treatment-related deaths were observed in this study. All 40 specimens were also diagnosed as HGNEC by central pathological review. CONCLUSIONS: The combination of irinotecan and cisplatin as postoperative adjuvant chemotherapy was feasible and possibly efficacious for resected HGNEC.

Tracheal ulcer due to Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

A 74-year-old man was referred to our hospital because of a tracheal stenosis circumscribed with soft tissue density and a left pulmonary nodule. Open biopsy of a right submandibular lymph node revealed diffuse large B-cell lymphoma, and the malignant cells were positive for Epstein-Barr virus gene products. Bronchofiberscopy revealed a tracheal necrotizing ulcer. After chemotherapy, the tracheal ulcer resolved. To our knowledge, this is the first report of a case of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly with a tracheal ulcer.

Probing DNA mismatched and bulged structures by using 19F NMR spectroscopy and oligodeoxynucleotides with an 19F-labeled nucleobase.

In this study, DNA local structures with bulged bases and mismatched base pairs as well as ordinary full-matched base pairs by using (19)F NMR spectroscopy with (19)F-labeled oligodeoxynucleotides (ODNs) were monitored. The chemical shift change in the (19) F NMR spectra allowed discrimination of the DNA structures. Two types of ODNs possessing the bis(trifluoromethyl)benzene unit (F-unit) at specified uridines were prepared and hybridized with their complementary or noncomplementary strands to form matched, mismatched, or bulged duplexes. By using ODN F1, in which an F-unit was connected directly to a propargyl amine-substituted uridine, three local structures, that is, full-matched, G-U mismatch, and A-bulge could be analyzed, whereas other structures could not be discriminated. A molecular modeling study revealed that the F-unit in ODN F1 interacted little with the nucleobases and sugar backbone of the opposite strand because the linker length between the F-unit and the uridine base was too short. Therefore, the capacity of ODN F1 to discriminate the DNA local structures was limited. Thus, ODN F2 was designed to improve this system; aminobenzoic acid was inserted between the F-unit and uridine base so the F-unit could interact more closely with the opposite strand. Eventually, the G-bulge and T-U mismatch and the three aforementioned local structures could be discriminated by using ODN F2. In addition, the dissociation processes of these duplexes could be monitored concurrently by (19)F NMR spectroscopy.

Electron transport through 5-substituted pyrimidines in DNA: electron affinities of uracil and cytosine derivatives differently affect the apparent efficiencies.

We investigated excess electron transport (EET) in DNA containing cytosine derivatives. By arranging the derivatives according to their electron affinities, the apparent EET efficiency was successfully regulated. Unexpectedly, however, providing gradients of electron affinity by inserting 5-fluorocytosine did not always enhance EET.

Novel porphyrin-psoralen conjugates: synthesis, DNA interaction and cytotoxicity studies.

A Cu(i)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) has been utilized to prepare novel triazole-linked cationic porphyrin-psoralen conjugates that exhibited significant photocytotoxicity against A549 cancer cells (IC50 = 84 nM).

Enzyme-catalyzed conversion of chemical structures on the surface of gold nanorods.

For developing metal nanoparticles of which surface chemical structures could be altered by enzymes in the cells, functional linkers caged by coumaric acids have been synthesized. Synthesized gold nanorod (GNR) conjugates possessing coumaric acid precursors underwent (porcine liver) esterase-catalyzed hydrolysis on their surface to afford GNRs coated with amino-functionalized polyethylene glycol and fluorescent coumarins as reporter molecules for monitoring the conversion. The chemical structural conversion on the GNR surfaces was successfully observed inside cells by fluorescence microscopy when GNR conjugates were incubated with tumor cells.

Cationic porphyrin-quinoxaline conjugate as a photochemically triggered novel cytotoxic agent.

A novel cationic porphyrin-quinoxaline conjugate 8 was prepared in good yield by the coupling of activated quinoxaline carboxylic acid 5 with an appropriate aminoporphyrin. The UV-vis spectra of conjugate 8 with the addition of ctDNA shows substantial hypochromicity (39%) and a red shift (12 nm) in the Soret band indicating intercalation and self stacking along the surface. The binding constant of conjugate 8 with ctDNA was determined to be 1.26×10(6) M(-1). The porphyrin-quinoxaline conjugate 8 displayed enhanced photocytotoxicity (IC50=0.06 µM) when compared to TMPyP against A549 cancer cells.

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated. METHODS: We enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined. RESULTS: Of 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF. CONCLUSIONS: The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion.