Controlled cavitation design and investigation of its effect in traumatic-brain injuries

Traumatic brain injuries (TBIs) are a highly complex injury that is heavily studied in modern research. An aspect of TBIs that has been almost entirely overlooked is the existence of cavitation in the brain during a high impact injury. The presence of cavitation in the brain is a recent theory and is feared to cause detrimental damages on brain tissue. The following chapters aim to investigate this phenomena by first engineering an apparats that simulates controlled cavitation for TBI applications. The apparatus that is used in this study involves acoustical techniques to cause microbubbles (MBs) to oscillate and fragment under resonant conditions, detailed in Chapter 2. MBs are created by using a syringe to push air through capillary tubing, resulting in MBs ranging from 50-100 μm. The MBs exit at a consistent rate and arbitrary amounts are adhered to an analyt sample prior to inducing acoustical cavitation. This method is advantageous and novel because it allows for arbitrary amounts of cavitation, the size of the created MBs is similar to that of what is thought to exist in vivo, and it is cost-effective. Using this developed apparatus, there are a variety of studies that have novel potential. Chapter 3 highlights the response the soft polymers have to surrounding cavitation. Using 3D confocal microscopy and interferometry techniques, it is apparent that the soft polymer surface is visually damaged after cavitation exposure. Further roughness calculations demonstrate distinct alterations in the overall roughness and skewness of the surface for experimental samples. Although these soft polymers do not entirely replicate the response to cavitation of the human brain, they provide insight on how alarming inter-cranial actually is and motivate future studies. Reactive astrocytes are known to have a large role in the response of the brain after a TBI. Introducing astrocytes in the developed apparatus is made possible by sterilizing all the components and using phosphate buffered saline (PBS) as the cavitation medium. Culturing astrocytes on biocompatible microfibers allows for the investigation of a finite amount of cells. Chapter 4 illustrates a distinct morphological change that the astrocytes undergo after experiencing cavitation. Over 48 hours different stages of morphology are represented. Chapter 4 also elucidates genetic changes that astrocytes undergo immediately after cavitation, via quantitative polymerase chain reaction (qPCR) techniques. Results show alarming upregulation in various genes that are known to be upregulated in other neurodegenerative diseases. These findings add additional concern for the damages that cavitation causes on nearby cranial anatomy. These results also inspired an additional genetic study to characterize the longitudinal gene expression trend from 0-48 hours post-cavitation, summarized in Chapter 5. This was primarily an exploratory study to help further investigate the morphological changes that were found in Chapter 4. In the ten genes that were studied, there was no consistent trend in gene expression from multiple genes to the next. Future studies aim to include RNA sequencing to obtain a complete summary on the expression changes in the entire genome. Taken together, the following chapters summarize the engineering of an applied apparatus that simulates controlled cavitation in vitro. Introducing soft polymers in this apparatus yields distinct surface alterations. This apparatus is biocompatible and used to study morphological and genetic changes in astrocytes. These results are novel and help legitimize the concerning detriments that cavitation has inside the human skull. Future studies aim to build on this foundation and continue to bolster the current understanding, therapeutics, and preventative techniques in TBIs

Controlled positioning of microbubbles and induced cavitation using a dual-frequency transducer and microfiber adhesion techniques

We report a study on two methods that enable spatial control and induced cavitation on targeted microbubbles (MBs). Cavitation is known to be present in many situations throughout nature. This phenomena has been proven to have the energy to erode alloys, like steel, in propellers and turbines. It is recently theorized that cavitation occurs inside the skull during a traumatic-brain injury (TBI) situation. Controlled cavitation methods could help better understand TBIs and explain how neurons respond at moments of trauma. Both of our approaches involve an ultrasonic transducer and bio-compatible Polycaprolactone (PCL) microfibers. These methods are reproducible as well as affordable, providing more control and efficiency compared to previous techniques found in literature. We specifically model three-dimensional spatial control of individual MBs using a 1.6 MHz transducer. Using a 100 kHz transducer, we also illustrate induced cavitation on an individual MB that is adhered to the surface of a PCL microfiber. The goal of future studies will involve characterization of neuronal response to cavitation and seek to unmask its linkage with TBIs

Microfibers as Physiologically Relevant Platforms for Creation of 3D Cell Cultures

Microfibers have received much attention due to their promise for creating flexible and highly relevant tissue models for use in biomedical applications such as 3D cell culture, tissue modeling, and clinical treatments. A generated tissue or implanted material should mimic the natural microenvironment in terms of structural and mechanical properties as well as cell adhesion, differentiation, and growth rate. Therefore, the mechanical and biological properties of the fibers are of importance. This paper briefly introduces common fiber fabrication approaches, provides examples of polymers used in biomedical applications, and then reviews the methods applied to modify the mechanical and biological properties of fibers fabricated using different approaches for creating a highly controlled microenvironment for cell culturing. It is shown that microfibers are a highly tunable and versatile tool with great promise for creating 3D cell cultures with specific properties

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

In-situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole using 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. A unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. Birefringent light propagation has been examined as a possible explanation for this effect. The predictions of a first-principles birefringence model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties do not only include the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube LED calibration data, the theory and parametrization of the birefringence effect, the fitting procedures of these parameterizations to experimental data as well as the inferred crystal properties.</p

Galactic Core-Collapse Supernovae at IceCube: “Fire Drill” Data Challenges and follow-up

The next Galactic core-collapse supernova (CCSN) presents a once-in-a-lifetime opportunity to make astrophysical measurements using neutrinos, gravitational waves, and electromagnetic radiation. CCSNe local to the Milky Way are extremely rare, so it is paramount that detectors are prepared to observe the signal when it arrives. The IceCube Neutrino Observatory, a gigaton water Cherenkov detector below the South Pole, is sensitive to the burst of neutrinos released by a Galactic CCSN at a level >10σ. This burst of neutrinos precedes optical emission by hours to days, enabling neutrinos to serve as an early warning for follow-up observation. IceCube\u27s detection capabilities make it a cornerstone of the global network of neutrino detectors monitoring for Galactic CCSNe, the SuperNova Early Warning System (SNEWS 2.0). In this contribution, we describe IceCube\u27s sensitivity to Galactic CCSNe and strategies for operational readiness, including "fire drill" data challenges. We also discuss coordination with SNEWS 2.0

All-Energy Search for Solar Atmospheric Neutrinos with IceCube

The interaction of cosmic rays with the solar atmosphere generates a secondary flux of mesons that decay into photons and neutrinos – the so-called solar atmospheric flux. Although the gamma-ray component of this flux has been observed in Fermi-LAT and HAWC Observatory data, the neutrino component remains undetected. The energy distribution of those neutrinos follows a soft spectrum that extends from the GeV to the multi-TeV range, making large Cherenkov neutrino telescopes a suitable for probing this flux. In this contribution, we will discuss current progress of a search for the solar neutrino flux by the IceCube Neutrino Observatory using all available data since 2011. Compared to the previous analysis which considered only high-energy muon neutrino tracks, we will additionally consider events produced by all flavors of neutrinos down to GeV-scale energies. These new events should improve our analysis sensitivity since the flux falls quickly with energy. Determining the magnitude of the neutrino flux is essential, since it is an irreducible background to indirect solar dark matter searches

TXS 0506+056 with Updated IceCube Data

Past results from the IceCube Collaboration have suggested that the blazar TXS 0506+056 is a potential source of astrophysical neutrinos. However, in the years since there have been numerous updates to event processing and reconstruction, as well as improvements to the statistical methods used to search for astrophysical neutrino sources. These improvements in combination with additional years of data have resulted in the identification of NGC 1068 as a second neutrino source candidate. This talk will re-examine time-dependent neutrino emission from TXS 0506+056 using the most recent northern-sky data sample that was used in the analysis of NGC 1068. The results of using this updated data sample to obtain a significance and flux fit for the 2014 TXS 0506+056 "untriggered" neutrino flare are reported

Recent neutrino oscillation results with the IceCube experiment

The IceCube South Pole Neutrino Observatory is a Cherenkov detector instrumented in a cubic kilometer of ice at the South Pole. IceCube’s primary scientific goal is the detection of TeV neutrino emissions from astrophysical sources. At the lower center of the IceCube array, there is a subdetector called DeepCore, which has a denser configuration that makes it possible to lower the energy threshold of IceCube and observe GeV-scale neutrinos, opening the window to atmospheric neutrino oscillations studies. Advances in physics sensitivity have recently been achieved by employing Convolutional Neural Networks to reconstruct neutrino interactions in the DeepCore detector. In this contribution, the recent IceCube result from the atmospheric muon neutrino disappearance analysis using the CNN-reconstructed neutrino sample are presented and compared to the existing worldwide measurements