Second-harmonic generation microscopy analysis reveals proteoglycan decorin is necessary for proper collagen organization in prostate.

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn  -    /    -  ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to the SHG coherence length, and found more disordered fibril organization in the Dcn  -    /    -  . We have also used image analysis readouts based on entropy, multifractal dimension, and wavelet transforms to compare the collagen fibril/fiber architecture in the two models, where all these showed that the Dcn  -    /    -   prostate comprised smaller and more disorganized collagen structures. All these SHG metrics are consistent with decreased SHG phase matching in the Dcn  -    /    -   and are further consistent with ultrastructural analysis of collagen in this model in other tissues, which show a more random distribution of fibril sizes and their packing into fibers. As Dcn is a known tumor suppressor, this work forms the basis for future studies of collagen remodeling in both malignant and benign prostate disease

GS-PAT: High-Speed Multi-Point Sound-Fields for Phased Arrays of Transducers

Phased Arrays of Transducers (PATs) allow accurate control of ultrasound fields, with applications in haptics, levitation (i.e. displays) and parametric audio. However, algorithms for multi-point levitation or tactile feedback are usually limited to computing solutions in the order of hundreds of sound-fields per second, preventing the use of multiple high-speed points, a feature that can broaden the scope of applications of PATs. We present GS-PAT, a GPU multi-point phase retrieval algorithm, capable of computing 17K solutions per second for up to 32 simultaneous points in a mid-end consumer grade GPU (NVidia GTX 1660). We describe the algorithm and compare it to state of the art multi-point algorithms used for ultrasound haptics and levitation, showing similar quality of the generated sound-fields, and much higher computation rates. We then illustrate how the shift in paradigm enabled by GS-PAT (i.e. real-time control of several high-speed points) opens new applications for PAT technologies, such as in volumetric fully coloured displays, multi-point spatio-temporal tactile feedback, parametric audio and simultaneous combinations of these modalities

Pion parameters in nuclear medium from chiral perturbation theory and virial expansion

We consider two methods to find the effective parameters of the pion traversing a nuclear medium. One is the first order chiral perturbation theoretic evaluation of the pion pole contribution to the two-point function of the axial-vector current. The other is the exact, first order virial expansion of the pion self-energy. We find that, although the results of chiral perturbation theory are not valid at normal nuclear density, those from the virial expansion may be reliable at such density. The latter predicts both the mass-shift and the in-medium decay width of the pion to be small, of about a few MeV.Comment: 9 Pages RevTex, 3 eps figure

The Exonuclease Activity of hPMC2 is Required for Transcriptional Regulation of The QR Gene and Repair of Estrogen-Induced Abasic Sites

We have previously reported that the expression of antioxidative stress enzymes is upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor β (ERβ) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERβ and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIβ (Topo IIβ) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, we found that hPMC2 is a 3\u27-5\u27 non-processive exonuclease that degrades both single-stranded and double-stranded substrates. Mutation of two conserved carboxylate residues drastically reduced the exonuclease activity of hPMC2, indicating the relative importance of the catalytic residues. Western blot analysis of breast cancer cell lines for Quinone Reductase (QR) levels revealed that the intrinsic exonuclease activity of hPMC2 was required for TOT-induced QR upregulation. Chromatin immunoprecipitation (ChIP) assays also indicated that hPMC2 was involved in the formation of strand breaks observed with TOT treatment and is specific for the EpRE-containing region of the QR gene. We also determined that the transcription factor NF-E2-related factor-2 (Nrf2) is involved in the specificity of hPMC2 for the EpRE. In addition, we determined that the catalytic activity of hPMC2 is required for repair of abasic sites that result from estrogen-induced DNA damage. Thus, our study provides a mechanistic basis for transcriptional regulation by hPMC2 and provides novel insights into its role in cancer prevention

TipTrap: A Co-located Direct Manipulation Technique for Acoustically Levitated Content

Acoustic levitation has emerged as a promising approach for mid-air displays, by using multiple levitated particles as 3D voxels, cloth and thread props, or high-speed tracer particles, under the promise of creating 3D displays that users can see, hear and feel with their bare eyes, ears and hands. However, interaction with this mid-air content always occurred at a distance, since external objects in the display volume (e.g. user's hands) can disturb the acoustic fields and make the particles fall. This paper proposes TipTrap, a co-located direct manipulation technique for acoustically levitated particles. TipTrap leverages the reflection of ultrasound on the users' skin and employs a closed-loop system to create functional acoustic traps 2.1 mm below the fingertips, and addresses its 3 basic stages: selection, manipulation and deselection. We use Finite-Differences Time Domain (FDTD) simulations to explain the principles enabling TipTrap, and explore how finger reflections and user strategies influence the quality of the traps (e.g. approaching direction, orientation and tracking errors), and use these results to design our technique. We then implement the technique, characterizing its performance with a robotic hand setup and finish with an exploration of the ability of TipTrap to manipulate different types of levitated content

Global research priorities for infections that affect the nervous system

Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries