<p> Every year, many thousands of people worldwide lose the ability to speak due to receiving a laryngectomy, typically for treatment of cancer. At some point in their recovery, most will use an electrolarynx to recover their ability to speak. Typical electrolarynxes utilize a piston to strike a disc pressed to the patient's neck which delivers a pressure wave into the soft tissue. This pressure wave mechanically couples with the vocal tract and generates the fundamental frequency necessary for creating vowels without which speech is not possible. </p><p> Commonly available electrolarynxes suffer from poor frequency control due to the nonlinear character of their impulse driver. They also create a great deal of "self-noise" which is distracting to listeners and makes using voice communication systems difficult. </p><p> We propose a novel electrolarynx implementation which utilizes two interfering ultrasonic waves to generate a fundamental frequency in the vocal tract required for speech restoration. The device is light weight, compact, inexpensive, and offers excellent control of all aspects of the output waveform. In addition, as the primary waveforms are above human hearing, there is little "self-noise" that can be heard by listeners and most communications devices filter such noise as part of their standard digitization process. </p><p> This device offers the potential to greatly improve the lives of those who have lost their voices and must rely on technology to allow them to communicate in the most efficient manner.</p>

Radiotherapy is the use of ionising radiation to induce localised DNA damage to cancerous tissues, leading to cell death and disease control. In order to maximise tumour growth control and to limit damage of the healthy surrounding tissues and the consequent side effects for the patient, molecular determinants of tumour radioresistance are investigated as potential clinical targets. A high-throughput siRNA colony formation assay screen in HeLa cervical carcinoma cells previously published by our laboratory identified modulators of radiosensitivity. From the list CSF1R, EPHB2, GAK and TOPK, were selected and validated. TOPK (T-LAK cell-originated protein kinase, also known as PDZ-binding kinase, PBK) was selected for further investigation because it is overexpressed in most malignancies but not in normal tissues, apart from testis and placenta. Knockdown of TOPK was shown to induce radiosensitisation in a panel of cancer cell lines with no significant effects on normal cells. A role for TOPK in the cell cycle response to ionising radiation (IR) was discovered in HCT116 colorectal cancer cells, with alterations in the G₁/S and G₂/M checkpoints. Furthermore, immunoprecipitation experiments identified a physical interaction between TOPK and CDKN1A (p21) at 8 hours after IR. Apoptosis and the number of multinucleated cells were significantly increased in TOPK depleted cells exposed to IR, suggesting the possibility of aberrant mitosis and mitotic catastrophe in these cells. High TOPK expression in early breast cancer patients was shown to be associated with poor recurrence-free survival. In addition, immunohistochemistry (IHC) analysis on samples from prostate cancer patients identified a strong correlation between high levels of TOPK and poor clinical response to radiotherapy. In order to facilitate future in vivo experiments, an HCT116 shRNA stable knockdown cell line was developed and two commercially available TOPK inhibitors were tested and optimised. Taken together, these data suggest that TOPK is a molecular determinant of radiosensitivity with a great potential for future clinical applications.

Acoustic focusing of microscale protein crystals with acoustophoresis technology could reduce clogs during experiments with the scientific technique serial femtosecond x-ray crystallography (SFX). SFX determines molecular structures of proteins, these structures are valuable in drug discovery and fundamental biomedical research. Lysozyme crystals were focused in their own mother liquor and dilutions with PBS buffer. The aim of these tests were to study how the acoustic contrast factor Φ changes with the medium. Recorded experiments were analyzed using the particle tracking software Trackmate to extract velocities and radii. The lysozyme crystals changed morphologies in large dilutions of PBS buffert, they either became rounder or broke into fragments. The changed forms are likely caused by dissolution behaviors; some dilutions were unstable, but not unstable enough to dissolve the crystals completely.  Measured velocities during focusing of the crystals had large variance. Sinusoidal fits of the velocities had significant increases in amplitudes for larger dilutions of PBS. A change in acoustic contrast factor Φ could be the cause for the increased amplitudes, but the results do not rule out other causes. There are currently major knowledge gaps about using protein crystals as particles with acoustophoresis technologies, hence many ideas for future works have been proposed in this master thesis report. / Akustisk fokusering av mikrometers-stora proteinkristaller med hjälp av ultraljudsteknik skulle kunna reducera proppar under experiment med tekniken seriell femtosekundskristallografi (SFX). SFX kan avgöra vilken struktur proteinmolekyler har, dessa strukturer är värdefulla för industriell utveckling av nya läkemedel och fundamental biomedicinsk forskning. Proteinkristaller av lysozym har fokuserats i sin egen kristalliseringslösning och utspädningar av PBS. Målet med de här experimenten var att se om den akustiska flödeskontrasten Φ kunde bli påverkad. Fokuseringar spelades in och partiklarnas hastigheter vid fokuseringarna mättes med hjälp av Trackmate (en mjukvara för partikelspårning). I de större utspädningarna förändrades lysozymkristallernas former, de blev antingen mer runda eller så blev de små bitar. Förändringen skedde förmodligen på grund av upplösningsmekanismer i instabila utspädningar.  Uppmätta hastigheter vid testerna hade stor varians, men kurvanpassningar av data tyder på att hastigheterna ökar signifikant med utspädningar av PBS. Den akustiska flödeskontrasten Φ kan vara orsaken för ökade hastigheter, men andra hypoteser gick inte att utesluta med resultaten. Stora kunskapshål finns om akustisk fokusering av proteinkristaller, därför har många idéer för framtida experiment och arbeten föreslagits i rapporten.