Molecular double core-hole electron spectroscopy for chemical analysis

We explore the potential of double core hole electron spectroscopy for chemical analysis in terms of x-ray two-photon photoelectron spectroscopy (XTPPS). The creation of deep single and double core vacancies induces significant reorganization of valence electrons. The corresponding relaxation energies and the interatomic relaxation energies are evaluated by CASSCF calculations. We propose a method how to experimentally extract these quantities by the measurement of single and double core-hole ionization potentials (IPs and DIPs). The influence of the chemical environment on these DIPs is also discussed for states with two holes at the same atomic site and states with two holes at two different atomic sites. Electron density difference between the ground and double core-hole states clearly shows the relaxations accompanying the double core-hole ionization. The effect is also compared with the sensitivity of single core hole ionization potentials (IPs) arising in single core hole electron spectroscopy. We have demonstrated the method for a representative set of small molecules LiF, BeO, BF, CO, N2, C2H2, C2H4, C2H6, CO2 and N2O. The scalar relativistic effect on IPs and on DIPs are briefly addressed.Comment: 35 pages, 6 figures. To appear in J. Chem. Phys

NavCog: turn-by-turn smartphone navigation assistant for people with visual impairments or blindness

NavCog is a novel smartphone navigation system for people with visual impairments or blindness, capable of assisting the users during autonomous mobility in complex and unfamiliar indoor/outdoor environments. The accurate localization achieved by NavCog is used for precise turn-by-turn way-finding assistance as the first step, but the ultimate goal is to present a variety of location based information to the user, such as points of interest gathered from social media and online geografic information services

Achieving Practical and Accurate Indoor Navigation for People with Visual Impairments

Methods that provide accurate navigation assistance to people with visual impairments often rely on instrumenting the environment with specialized hardware infrastructure. In particular, approaches that use sensor networks of Bluetooth Low Energy (BLE) beacons have been shown to achieve precise localization and accurate guidance while the structural modifications to the environment are kept at minimum. To install navigation infrastructure, however, a number of complex and time-critical activities must be performed. The BLE beacons need to be positioned correctly and samples of Bluetooth signal need to be collected across the whole environment. These tasks are performed by trained personnel and entail costs proportional to the size of the environment that needs to be instrumented. To reduce the instrumentation costs while maintaining a high accuracy, we improve over a traditional regression-based localization approach by introducing a novel, graph-based localization method using Pedestrian Dead Reckoning (PDR) and particle filter. We then study how the number and density of beacons and Bluetooth samples impact the balance between localization accuracy and set-up cost of the navigation environment. Studies with users show the impact that the increased accuracy has on the usability of our navigation application for the visually impaired

Treatment Strategy for Recurrent and Refractory Epithelial Ovarian Cancer: Efficacy of High-Dose Chemotherapy with Hematopoietic Stem Cell Transplantation

According to population statistics in Japan, approximately 3,800 women die of ovarian ­cancer annually, and approximately 6,000 are affected by this disease. Ovarian cancer is ­referred to as a “silent tumor”, since patients have few subjective symptoms and by the time symptoms are observed, the cancer has progressed to Stage III or IV in about half of the patients. The basic treatment for advanced epithelial ovarian cancer is to remove as much of the tumor as possible, and subsequently to perform anticancer therapy using drugs such as cisplatin, carboplatin and paclitaxel, all of which have been shown to be effective for epi­thelial ovarian cancer. However, the 5-year survival rate in advanced ovarian cancer patients is still only about 20%, and a treatment that leads to long-term survival has yet to be developed. Here, we review the available treatments for ovarian cancer, and present the results of high-dose chemotherapy (HDC) performed in our hospital for recurrent and refractory ­ovarian cancer

Breaking The Exclusionary Boundary Between User Experience And Access: Steps Toward Making UX Inclusive Of Users With Disabilities

This research paper points out that we as Designers have failed to come up with a model of UX that would proximate a satisfying user experience for users with disabilities. It underscores the gaps in designer knowledge about disabled bodies. The research paper also draws the attention of the designer community to the limited understanding we presently possess of the disabled people\u27s notions of, and expectations from, satisfying user experiences. It proposes a multi-step process for shifting the focus of design activity from a medical model of accessibility design that retrofits normative designs to the needs of users with disabilities to developing an accessible user experience model (AUX) of design that counts these users as design collaborators, possessors of special knowledge about disabled bodies, and untapped sources of innovative designs that might offer additional design features for all users

Response of the Great Barrier Reef to sea level and environmental changes over the past 30,000 years

Previous drilling through submerged fossil coral reefs has greatly improved our understanding of the general pattern of sea-level change since the Last Glacial Maximum, however, how reefs responded to these changes remains uncertain. Here we document the evolution of the Great Barrier Reef (GBR), the world\u27s largest reef system, to major, abrupt environmental changes over the past 30 thousand years based on comprehensive sedimentological, biological and geochronological records from fossil reef cores. We show that reefs migrated seaward as sea level fell to its lowest level during the most recent glaciation (~20.5-20.7 thousand years ago (ka)), then landward as the shelf flooded and ocean temperatures increased during the subsequent deglacial period (~20-10 ka). Growth was interrupted by five reef-death events caused by subaerial exposure or sea-level rise outpacing reef growth. Around 10 ka, the reef drowned as the sea level continued to rise, flooding more of the shelf and causing a higher sediment flux. The GBR\u27s capacity for rapid lateral migration at rates of 0.2-1.5 m yr−1 (and the ability to recruit locally) suggest that, as an ecosystem, the GBR has been more resilient to past sea-level and temperature fluctuations than previously thought, but it has been highly sensitive to increased sediment input over centennial-millennial timescales

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14.Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

<p>Abstract</p> <p>Background</p> <p>Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.</p> <p>Methods</p> <p>The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.</p> <p>Results</p> <p>ECI carrying a chitobiose unit, ECI-(GlcNAc) ₂, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)₃(GlcNAc)₂], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)₂.</p> <p>Conclusions</p> <p>Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.</p