The effects of alveolar bone socket geometry and bone-implant contact on implant biomechanics, and resulting strain distributions in bone were investigated. Following extraction of lateral incisors on a cadaver mandible, implants were placed immediately and bone-implant contact area, stability implant biomechanics and bone strain were measured. In situ biomechanical testing coupled with micro X-ray microscopy (μ-XRM) illustrated less stiff bone-implant complexes (701-822. N/mm) compared with bone-periodontal ligament (PDL)-tooth complexes (791-913. N/mm). X-ray tomograms illustrated that the cause of reduced stiffness was due to limited bone-implant contact. Heterogeneous elemental composition of bone was identified by using energy dispersive X-ray spectroscopy (EDS). The novel aspect of this study was the application of a new experimental mechanics method, that is, digital volume correlation, which allowed mapping of strains in volumes of alveolar bone in contact with a loaded implant. The identified surface and subsurface strain concentrations were a manifestation of load transferred to bone through bone-implant contact based on bone-implant geometry, quality of bone, implant placement, and implant design. 3D strain mapping indicated that strain concentrations are not exclusive to the bone-implant contact regions, but also extend into bone not directly in contact with the implant. The implications of the observed strain concentrations are discussed in the context of mechanobiology. Although a plausible explanation of surgical complications for immediate implant treatment is provided, extrapolation of results is only warranted by future systematic studies on more cadaver specimens and/or in vivo models.

The structure and evolution of the ion temperature (Ti) and toroidal rotation (V-) profile have been investigated in neutral beam injection (NBI)-heated KSTAR H-mode plasmas, both without and with resonant magnetic pertubations (RMPs). A clear disparity between the width of the ∇Vφpedestal and that of the ∇Ti-pedestal was observed. Also, it was found that there exists a close correlation and weak relative hysteresis between the pedestal ∇Vφand ∇Ti during both L →H and H →L transitions. During the L →H transition, the Vφpedestal is observed to form ahead of the Ti-pedestal, and build inward from the separatrix. Linear gyrokinetic stability analysis of these KSTAR profiles was performed. The results indicate that parallel velocity shear is a relevant drive for pedestal turbulence and transport. This was largely ignored in previous studies of the pedestal micro-stability. Pedestal ion temperature and rotation profiles were also measured during edge localized mode (ELM) suppression experiments on KSTAR using an n = 1 RMPs. It was found that the top values of the ion temperature and toroidal rotation pedestal drop with RMPs when ELMs are suppressed.

The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated β-galactosidase (SA-β-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.

Laser pump-X-ray probe experiments require control over the X-ray pulse pattern and timing. Here, the first use of pseudo-single-bunch mode at the Advanced Light Source in picosecond time-resolved X-ray absorption experiments on solutions and solids is reported. In this mode the X-ray repetition rate is fully adjustable from single shot to 500 kHz, allowing it to be matched to typical laser excitation pulse rates. Suppressing undesired X-ray pulses considerably reduces detector noise and improves signal to noise in time-resolved experiments. In addition, dose-induced sample damage is considerably reduced, easing experimental setup and allowing the investigation of less robust samples. Single-shot X-ray exposures of a streak camera detector using a conventional non-gated charge-coupled device (CCD) camera are also demonstrated.

Subcortical vascular dementia (SVaD), one of common causes of dementia, has concomitant Alzheimer's disease (AD) pathology in over 30%, termed "mixed dementia". Identifying mixed dementia from SVaD is important because potential amyloid-targeted therapies

Electromagnetic ion cyclotron (EMIC) waves play important roles in particle loss processes in the magnetosphere. Determining the evolution of EMIC waves as they propagate and how this evolution affects wave-particle interactions requires accurate knowledge of the wave vector, k. We present a technique using the curl of the wave magnetic field to determine k observationally, enabled by the unique configuration and instrumentation of the Magnetospheric MultiScale (MMS) spacecraft. The wave curl analysis is demonstrated for synthetic arbitrary electromagnetic waves with varying properties typical of observed EMIC waves. The method is also applied to an EMIC wave interval observed by MMS on October 28, 2015. The derived wave properties and k from the wave curl analysis for the observed EMIC wave are compared with the Waves in Homogenous, Anisotropic, Multi-component Plasma (WHAMP) wave dispersion solution and with results from other single- and multi-spacecraft techniques. We find good agreement between k from the wave curl analysis, k determined from other observational techniques, and k determined from WHAMP. Additionally, the variation of k due to the time and frequency intervals used in the wave curl analysis is explored. This exploration demonstrates that the method is robust when applied to a wave containing at least 3-4 wave periods and over a rather wide frequency range encompassing the peak wave emission. These results provide confidence that we are able to directly determine the wave vector properties using this multi-spacecraft method implementation, enabling systematic studies of EMIC wave k properties with MMS.

Background and purpose

The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized.

Methods

Forty-five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited.

Results

Compared with NC, patients with PiB(-) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(-) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(-) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(-) SVaD. Compared with NC subjects, patients with PiB(-) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(-) SVaD exhibited additional deformities within the lateral head and inferior body.

Conclusions

Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.