Silicon photonics devices for integrated analog signal processing and sampling

Silicon photonics offers the possibility of a reduction in size weight and power for many optical systems, and could open up the ability to build optical systems with complexities that would otherwise be impossible to achieve. Silicon photonics is an emerging technology that has already been inserted into commercial communication products. This technology has also been applied to analog signal processing applications. MIT Lincoln Laboratory in collaboration with groups at MIT has developed a toolkit of silicon photonic devices with a focus on the needs of analog systems. This toolkit includes low-loss waveguides, a high-speed modulator, ring resonator based filter bank, and all-silicon photodiodes. The components are integrated together for a hybrid photonic and electronic analog-to-digital converter. The development and performance of these devices will be discussed. Additionally, the linear performance of these devices, which is important for analog systems, is also investigated

VEGF-A and Semaphorin3A: Modulators of vascular sympathetic innervation

AbstractSympathetic nerve activity regulates blood pressure by altering peripheral vascular resistance. Variations in vascular sympathetic innervation suggest that vascular-derived cues promote selective innervation of particular vessels during development. As axons extend towards peripheral targets, they migrate along arterial networks following gradients of guidance cues. Collective ratios of these gradients may determine whether axons grow towards and innervate vessels or continue past non-innervated vessels towards peripheral targets. Utilizing directed neurite outgrowth in a three-dimensional (3D) co-culture, we observed increased axon growth from superior cervical ganglion explants (SCG) towards innervated compared to non-innervated vessels, mediated in part by vascular endothelial growth factor (VEGF-A) and Semaphorin3A (Sema3A) which both signal via neuropilin-1 (Nrp1). Exogenous VEGF-A, delivered by high-expressing VEGF-A–LacZ vessels or by rhVEGF-A/alginate spheres, increased sympathetic neurite outgrowth while exogenous rhSema3A/Fc decreased neurite outgrowth. VEGF-A expression is similar between the innervated and non-innervated vessels examined. Sema3A expression is higher in non-innervated vessels. Spatial gradients of Sema3A and VEGF-A may promote differential Nrp1 binding. Vessels expressing high levels of Sema3A favor Nrp1-PlexinA1 signaling, producing chemorepulsive cues limiting sympathetic neurite outgrowth and vascular innervation; while low Sema3A expressing vessels favor Nrp1-VEGFR2 signaling providing chemoattractive cues for sympathetic neurite outgrowth and vascular innervation

Ultrasound-triggered antibiotic release from PEEK clips to prevent spinal fusion infection: Initial evaluations.

Despite aggressive peri-operative antibiotic treatments, up to 10% of patients undergoing instrumented spinal surgery develop an infection. Like most implant-associated infections, spinal infections persist through colonization and biofilm formation on spinal instrumentation, which can include metal screws and rods for fixation and an intervertebral cage commonly comprised of polyether ether ketone (PEEK). We have designed a PEEK antibiotic reservoir that would clip to the metal fixation rod and that would achieve slow antibiotic release over several days, followed by a bolus release of antibiotics triggered by ultrasound (US) rupture of a reservoir membrane. We have found using human physiological fluid (synovial fluid), that higher levels (100–500 μg) of vancomycin are required to achieve a marked reduction in adherent bacteria vs. that seen in the common bacterial medium, trypticase soy broth. To achieve these levels of release, we applied a polylactic acid coating to a porous PEEK puck, which exhibited both slow and US-triggered release. This design was further refined to a one-hole or two-hole cylindrical PEEK reservoir that can clip onto a spinal rod for clinical use. Short-term release of high levels of antibiotic (340 ± 168 μg), followed by US-triggered release was measured (7420 ± 2992 μg at 48 h). These levels are sufficient to prevent adhesion of Staphylococcus aureus to implant materials. This study demonstrates the feasibility of an US-mediated antibiotic delivery device, which could be a potent weapon against spinal surgical site infection. Statement of Significance: Spinal surgical sites are prone to bacterial colonization, due to presence of instrumentation, long surgical times, and the surgical creation of a dead space (≥5 cm 3 ) that is filled with wound exudate. Accordingly, it is critical that new approaches are developed to prevent bacterial colonization of spinal implants, especially as neither bulk release systems nor controlled release systems are available for the spine. This new device uses non-invasive ultrasound (US) to trigger bulk release of supra-therapeutic doses of antibiotics from materials commonly used in existing surgical implants. Thus, our new delivery system satisfies this critical need to eradicate surviving bacteria, prevent resistance, and markedly lower spinal infection rates

Myeloid suppressor cell depletion augments antitumor activity in lung cancer.

BackgroundMyeloid derived suppressor cells (MDSC) are important regulators of immune responses. We evaluated the mechanistic role of MDSC depletion on antigen presenting cell (APC), NK, T cell activities and therapeutic vaccination responses in murine models of lung cancer.Principal findingsIndividual antibody mediated depletion of MDSC (anti-Gr1 or anti-Ly6G) enhanced the antitumor activity against lung cancer. In comparison to controls, MDSC depletion enhanced the APC activity and increased the frequency and activity of the NK and T cell effectors in the tumor. Compared to controls, the anti-Gr1 or anti-Ly6G treatment led to increased: (i) CD8 T cells, (ii) NK cells, (iii) CD8 T or NK intracytoplasmic expression of IFNγ, perforin and granzyme (iv) CD3 T cells expressing the activation marker CD107a and CXCR3, (v) reduced CD8 T cell IL-10 production in the tumors (vi) reduced tumor angiogenic (VEGF, CXCL2, CXCL5, and Angiopoietin1&2) but enhanced anti-angiogenic (CXCL9 and CXCL10) expression and (vii) reduced tumor staining of endothelial marker Meca 32. Immunocytochemistry of tumor sections showed reduced Gr1 expressing cells with increased CD3 T cell infiltrates in the anti-Gr1 or anti-Ly6G groups. MDSC depletion led to a marked inhibition in tumor growth, enhanced tumor cell apoptosis and reduced migration of the tumors from the primary site to the lung compared to controls. Therapeutic vaccination responses were enhanced in vivo following MDSC depletion with 50% of treated mice completely eradicating established tumors. Treated mice that rejected their primary tumors acquired immunological memory against a secondary tumor challenge. The remaining 50% of mice in this group had 20 fold reductions in tumor burden compared to controls.SignificanceOur data demonstrate that targeting MDSC can improve antitumor immune responses suggesting a broad applicability of combined immune based approaches against cancer. This multifaceted approach may prove useful against tumors where MDSC play a role in tumor immune evasion

Modeled Microgravity Disrupts Collagen I/Integrin Signaling During Osteoblastic Differentiation of Human Mesenchymal Stem Cells

Spaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following seven days culture in modeled microgravity. One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen-integrin interactions and reduced integrin signaling. Integrins are heterodimeric transmembrane receptors that bind extracellular matrix proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of modeled microgravity on integrin expression and function in hMSC. We demonstrate that seven days of culture in modeled microgravity leads to reduced expression of the extracellular matrix protein, type I collagen (Col I). Conversely, modeled microgravity consistently increases Col I-specific alpha2 and beta1 integrin protein expression. Despite this increase in integrin sub-unit expression, autophosphorylation of adhesion-dependent kinases, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), is significantly reduced. Activation of Akt is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras-MAPK pathway is evidenced by a reduction in Ras and ERK activation. Taken together, our findings indicate that modeled microgravity decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis

Bridging Indigenous and science-based knowledge in coastal and marine research, monitoring, and management in Canada

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Drawing upon multiple types of knowledge (e.g., Indigenous knowledge, local knowledge, science-based knowledge) strengthens the evidence-base for policy advice, decision making, and environmental management. While the benefits of incorporating multiple types of knowledge in environmental research and management are many, doing so has remained a challenge. This systematic map examined the extent, range, and nature of the published literature (i.e., commercially published and grey) that seeks to respectively bridge Indigenous and science-based knowledge in coastal and marine research and management in Canada. Methods This systematic map applied standardized search terms across four databases focused on commercially published literature, carefully selected specialist websites, and two web-based search engines. In addition, reference sections of relevant review articles were cross-checked to identify articles that may not have been found using the search strategy. Search results were screened in two sequential stages; (1) at title and abstract; and (2) at full text following a published protocol. All case studies included were coded using a standard questionnaire. A narrative synthesis approach was used to identify trends in the evidence, knowledge gaps, and knowledge clusters. Results A total of 62 articles that spanned 71 Canadian case studies were included in the systematic map. Studies across the coastal and marine regions of Inuit Nunangat accounted for the majority of the studies. Whether the focus is on management and decision making or research and monitoring, the predominant ecological scale was at the species level, accounting for over two-thirds of the included studies. There were 24 distinct coastal and marine species of central focus across the studies. Nunavut had the greatest taxonomic coverage as studies conducted to date cover 13 different genera. The predominant methodology employed for combining and/or including Indigenous knowledge was case study design, which accounted for over half of the studies. Other methodologies employed for combining and/or including different ways of knowing included: (i) community-based participatory research; (ii) mixed methods; (iii) ethnography; and (iv) simulation modelling. There are a suite of methods utilized for documenting and translating Indigenous knowledge and an equally diverse tool box of methods used in the collection of scientific data. Over half of the case studies involved Indigenous knowledge systems of the Inuit, while another significant proportion involved Indigenous knowledge systems of First Nations, reflecting 21 unique nations. We found that demographics of knowledge holders were generally not reported in the articles reviewed. Conclusions The results of this systematic map provide key insights to inform and improve future research. First, a variety of methodologies and methods are used in these types of studies. Therefore, there is a need to consider in more detail how Indigenous and science-based knowledge systems can be respectively bridged across subjects while also recognizing specific place-based needs of Indigenous communities. Second, the work highlights the need to better report the demographics of knowledge holders. Further inquiry focused on the extent of knowledge co-production and assessing Indigenous participation across different stages of the research process would serve the research community well to improve future research and monitoring in support of, and to strengthen, evidence-based environmental management

Short Term Development and Fate of MGE-Like Neural Progenitor Cells in Jaundiced and Non-Jaundiced Rat Brain

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Neonatal hyperbilirubinemia targets specific brain regions and can lead to kernicterus. One of the most debilitating symptoms of kernicterus is dystonia, which results from bilirubin toxicity to the globus pallidus (GP). Stem cell transplantation into the GP to replace lost neurons and restore basal ganglia circuits function is a potential therapeutic strategy to treat dystonia in kernicterus. In this study we transplanted human medial ganglionic eminence (MGE)-like neural progenitor cells (NPCs) that we differentiated into a primarily gamma-aminobutyric acid (GABA)ergic phenotype, into the GP of non-immunosuppressed jaundiced (jj) and non-jaundiced (Nj) rats. We assessed the survival and development of graft cells at three time-points post-transplantation. While grafted MGE-like NPCs survived and generated abundant fibers in both jj and Nj brains, NPC survival was greater in the jj brain. These results were consistent with our previous finding that excitatory spinal interneuron-like NPCs exhibited a higher survival rate in the jj brain than in the Nj brain. Our findings further support our hypothesis that slightly elevated bilirubin levels in the jj brain served as an antioxidant and immunosuppressant to protect the transplanted cells. We also identified graft fibers growing toward brain regions that receive projections from the GP, as well as host fibers extending toward the graft. These promising findings suggest that MGE-like NPCs may have the capacity to restore the circuits connecting GP and other nuclei.NIH Center of Biomedical Research Excellence program project P20 GM104936Children's Mercy HospitalRonald D. Deffenbaugh FoundationKansas Intellectual and Developmental Disabilities Research Center HD09021

Electrochemical Deposition and Characterization of Fe₃O₄ Films Produced by the Reduction of Fe(III)-triethanolamine

In this paper, we demonstrate that films of magnetite, Fe3O4, can be deposited by the electrochemical reduction of a Fe(III)-triethanolamine complex in aqueous alkaline solution. the films were deposited with a columnar microstructure and a [100] preferred orientation on stainless steel substrates. In-plane electrical transport and magnetoresistance measurements were performed on the films after they were stripped off onto glass substrates. the resistance of the films was dependent on the oxygen partial pressure. We attribute the increase in resistance in O2 and the decrease in resistance in Ar to the oxidation and reduction of grain boundaries. the decrease in resistance in an Ar atmosphere exhibited first-order kinetics, with an activation energy of 0.2 eV. the temperature dependence of the resistance showed a linear dependence of log(R) versus T-1/2, consistent with tunneling across resistive grain boundaries. a room-temperature magnetoresistance of -6.5% was observed at a magnetic field of 9 T