Dark state lasers

We propose a new type of laser resonator based on imaginary "energy-level splitting" (imaginary coupling, or quality factor Q splitting) in a pair of coupled microcavities. A particularly advantageous arrangement involves two microring cavities with different free-spectral ranges (FSRs) in a configuration wherein they are coupled by "far-field" interference in a shared radiation channel. A novel Vernier-like effect for laser resonators is designed where only one longitudinal resonant mode has a lower loss than the small signal gain and can achieve lasing while all other modes are suppressed. This configuration enables ultra-widely tunable single-frequency lasers based on either homogeneously or inhomogeneously broadened gain media. The concept is an alternative to the common external cavity configurations for achieving tunable single-mode operation in a laser. The proposed laser concept builds on a high-Q "dark state" that is established by radiative interference coupling and bears a direct analogy to parity-time (PT) symmetric Hamiltonians in optical systems. Variants of this concept should be extendable to parametric-gain based oscillators, enabling use of ultrabroadband parametric gain for widely tunable single-frequency light sources

Tunable coupled-mode dispersion compensation and its application to on-chip resonant four-wave mixing

We propose and demonstrate localized mode coupling as a viable dispersion engineering technique for phase-matched resonant four-wave mixing (FWM). We demonstrate a dual-cavity resonant structure that employs coupling-induced frequency splitting at one of three resonances to compensate for cavity dispersion, enabling phase-matching. Coupling strength is controlled by thermal tuning of one cavity enabling active control of the resonant frequency-matching. In a fabricated silicon microresonator, we show an 8 dB enhancement of seeded FWM efficiency over the non-compensated state. The measured four-wave mixing has a peak wavelength conversion efficiency of -37.9 dB across a free spectral range (FSR) of 3.334 THz ($\sim$27 nm). Enabled by strong counteraction of dispersion, this FSR is, to our knowledge, the largest in silicon to demonstrate FWM to date. This form of mode-coupling-based, active dispersion compensation can be beneficial for many FWM-based devices including wavelength converters, parametric amplifiers, and widely detuned correlated photon-pair sources. Apart from compensating intrinsic dispersion, the proposed mechanism can alternatively be utilized in an otherwise dispersionless resonator to counteract the detuning effect of self- and cross-phase modulation on the pump resonance during FWM, thereby addressing a fundamental issue in the performance of light sources such as broadband optical frequency combs

Antisense oligonucleotide-mediated alternative splicing strategies to treat the type-1 fibrillinopathies

The type-1 fibrillinopathies are a family of connective tissue disorders of which Marfan syndrome is the most common, affecting between 2-3 in 10,000 individuals. Marfan syndrome is a multisystem disorder characterised by ocular, skeletal and cardiovascular abnormalities and can be caused by any one of over 2800 unique mutations reported across the fibrillin-1 (FBN1) gene. FBN1 encodes the large extracellular glycoprotein, fibrillin-1; the fibrillin-1 monomers aggregate to form the backbone of microfibrils. Fibrillin-1 has both structural and regulatory roles, including the regulation of transforming growth factor-beta. This regulation is critical in maintaining extracellular matrix stability and dysregulation of this function is one of the keystones of the Marfan syndrome pathogenesis. Mutations in FBN1 can result in reduced fibrillin-1 expression, loss-of-function or the production of two different fibrillin-1 proteins that are unable to interact to form functional microfibrils. The result in all three cases is a lack of functional microfibrils and destabilisation of the extracellular matrix. The current standard of care relies heavily on surgical intervention and lifelong use of medications to slow disease progression, thus the need for new therapeutic options that target the cause of disease. This thesis focused on developing a suite of short synthetic nucleic acid sequences, known as antisense oligonucleotides, to selectively manipulate FBN1 pre-mRNA splicing. We hypothesised that the removal of an amenable mutation-associated exon would result in one of the following scenarios. For missense mutations, removing the mutation-associated exon from affected and unaffected transcripts would eliminate the aberrant sequence and restore homogeneity between fibrillin-1 monomers. For splice-site and in-frame deletion mutations, excluding the mutation-associated exon from the remaining healthy transcripts would restore the domain periodicity and monomer homogeneity. Lastly, for mutations resulting in a premature termination codon, excluding the mutation-associated exon from the affected transcripts would restore the reading frame, rescuing transcript functionality. The mutation-associated exon would also need to be removed from the unaffected transcripts to maintain monomer homogeneity. For each of these scenarios, we hypothesised that the internally truncated proteins produced would be capable of forming functional microfibrils, thereby reducing the severity or slowing the progression of the Marfan syndrome phenotype. As an initial proof-of-concept for this project, antisense oligonucleotide sequences targeting FBN1 exon 52 were assessed. A promising sequence induced dose-dependent exon skipping in healthy control cells allowing us to observe the formation of healthy fibrillin-1 fibres with 0% exon skipping, loss of extruded fibrillin-1 fibres with 50% skipping; mimicking the disease-like state, and subsequent re-appearance of extracellular fibrillin-1 fibres with greater than 80% skipping indicating that the internally truncated fibrillin-1 monomers are capable of forming aggregates. Similarly, we demonstrate that FBN1 exons 47 and 59 can be efficiently excluded, and sufficient skipping can result in fibrillin-1 fibre formation. However, many of the FBN1 exons targeted were not as readily excised from the mature mRNA. Comparison of three antisense oligonucleotide chemistries revealed the promising efficacy of the newer thiophosphoramidate morpholino oligomer chemistry. Similar to the commonly used phosphorodiamidate morpholino oligomer, the thiophosphoramidate morpholino oligomer sequences resulted in efficient and consistent FBN1 exon 52 skipping. Both chemistries also had little effect on paraspeckle protein distribution, an indicator of toxicity, unlike the third, 2′OMe-PS, chemistry that caused gross paraspeckle protein disruption. Therefore, thiophosphoramidate morpholino oligomer should be included in the repertoire of chemistries routinely used in studies developing antisense therapeutics. Lastly, while we demonstrate that >80% exon skipping can lead to fibrillin-1 microfibril-like formations in vitro, we could not confirm the functionality of these fibres nor the effect of exon skipping on the Marfan syndrome phenotype. Nevertheless, this study demonstrates proof-of-concept and lays a solid foundation for further development of antisense oligonucleotides to treat the type-1 fibrillinopathies

Optimizing the selection and implementation of assembly line equipment at a large automobile original equipment manufacturer

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Ocean Engineering; in conjunction with the Leaders for Manufacturing Program at MIT, 2005.Includes bibliographical references (p. 96-97).Toyota Motor Manufacturing North America (TMMNA) is continuing to face an increasingly competitive automobile market. To meet these evolving market conditions, TMMNA has experienced rapid growth in demand for its automobiles in North America. To meet this demand, Toyota has rapidly grown from three assembly plants in the mid- 1990's to its current total of six assembly plants (five in operation with one being built). This has led to many management challenges, including communication, knowledge sharing, and knowledge retention that many companies experience when faced with rapid growth. In order to respond to these challenges, Vehicle Production Engineering (VPE) Assembly, a department within TMMNA, has attempted to develop a process through which it can standardize its processes and capitalize on best practices across the many North American plants. This thesis studied the process through which VPE Assembly develops and installs assembly line equipment for major automobile model changes. This study included observation of the Toyota product development process and how this process is carried out within VPE Assembly. This research revealed that the assembly line equipment process employed by Toyota is well suited for this organization. However, there are improvements available that could improve the overall process and bring automobiles models to the market more quickly. Communication between the different plants could be improved. Additionally, much knowledge learned from completed projects is not being shared fully between the various plants. Suggested improvements to address these problems are discussed.by Cale M. Holman.S.M.M.B.A

Prosthetic Thumb

The Prosthetic Thumb Project is a senior design project completed by Biomedical Engineering Undergraduate students at California Polytechnic State University. This senior design project is aimed at designing a prosthetic thumb for a Cal Poly Pomona student who lost their thumb in an accident last year. The patient has ultimately lost between 30-40% of functionality of his left hand, and so we would like to give him that mobility back. Originally, the patient was worried about having a prosthesis, and wanted something more stagnant that would resemble the look of the thumb he lost. However, after working with him, we determined that in order to regain functionality of the left hand, he would need a body-powered prosthesis that will move with his thumb residual in order to mimic the natural motion of a hand. Since we are designing a product for our customer, we still wanted to make a design that does not entirely look mechanical. The prototype of our design was generated using the 3D printers at innovation sandbox. Our parts were printed using PLA in order to utilize the free resources to students and keep the cost of the prosthetic low. When undergoing compression testing, the parts were tested using the instron in the Biomedical Engineering lab. The proximal and distal pieces were secured, and tested up to a force of 500 N. The proximal pieces experienced minor cracks, but still withstood the overall force without any internal support. The distal pieces withstood the force of 500 N with no cracks when the force can from the side. We also tested using a “hyper-extension” method, meaning we secured the prosthetic to a model of the hand, and hung weights off of the distal piece. The Prosthetic Thumb Group will be working on the final product that is being delivered to the patient next quarter as well. We plan on changing the material of the 3D printed parts to give the prosthetic thumb more strength

Biomechanical Foot Guidance Linkage

A gait replication apparatus can include a scalable mechanical mechanism configured to replicate different gaits . The scalable mechanical mechanism can include , for example , a four - bar linkage , a pantograph , a cam / Scotch - yoke mechanism , and so forth . In some embodiments , the mechanical mechanism includes a beam rotating about an axis passing proximate to its center , with a foot pedal slidably coupled with the beam , and a timing chain / belt or cable pulley - pair coupled with the foot pedal and looped about the beam . A method can include decomposing a foot path defined by Cartesian coordinates into polar coordinates , and providing a mechanical support for a foot , where a first mechanism controls an angular position of the mechanical support with respect to a reference frame , and a second mechanism controls a radial distance of the mechanical support from the reference frame

Evaluating the Viability of Graphene Oxide for the Removal of Ni(II) Ions From Waste Water

When levels of heavy metal ions such as nickel (Ni), copper (Cu), lead (Pb), Zinc (Zn), and Cobalt (Co) exceed the tolerance values for industrial wastewater, it can devastate the environment as well as the health of the individuals consuming the water. Heavy metal ions are not biodegradable and will accumulate in organic matter.(1) This accumulation leads to toxic levels in the blood and hence damage to nerve tissue, kidneys, the liver, and other vital organs. (2) Effective removal processes of these heavy metals from water must be developed. This study explores a method to adsorb nickel from water with graphene-based materials. Adsorption is used because it is cost effective and relatively simple. Concentration and pH dependent batch tests were performed to measure the nickel adsorption onto graphene oxide that had been prepared via the Hummer’s method. Our results show graphene oxide uptake values reached up to 365.9 mg of Ni(II) per gram of GO. The results also demonstrate that there was a strong impact from pH on graphene oxide uptake of Ni(II)

Students Create \u27Flash Marketing\u27 Business Model

Some business students hope to succeed in their eventual careers and have little real-world experience before graduating. Three students from the Jon M. Huntsman School of Business have experienced success in business long before their degrees at USU are finished.https://digitalcommons.usu.edu/huntsman_news/1096/thumbnail.jp

Aboriginal Resource Access in Response to Criminal Victimization in an Urban Context

Arts, Education and LawNo Full Tex

C1 inhibitor deficiency: 2014 United Kingdom consensus document

C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organisation. This article is protected by copyright. All rights reserved