Engineering Hybrid Epitaxial InAsSb/Al Nanowire Materials for Stronger Topological Protection

The combination of strong spin-orbit coupling, large $g$-factors, and the coupling to a superconductor can be used to create a topologically protected state in a semiconductor nanowire. Here we report on growth and characterization of hybrid epitaxial InAsSb/Al nanowires, with varying composition and crystal structure. We find the strongest spin-orbit interaction at intermediate compositions in zincblende InAs$_{1-x}$Sb$_{x}$ nanowires, exceeding that of both InAs and InSb materials, confirming recent theoretical studies \cite{winkler2016topological}. We show that the epitaxial InAsSb/Al interfaces allows for a hard induced superconducting gap and 2$e$ transport in Coulomb charging experiments, similar to experiments on InAs/Al and InSb/Al materials, and find measurements consistent with topological phase transitions at low magnetic fields due to large effective $g$-factors. Finally we present a method to grow pure wurtzite InAsSb nanowires which are predicted to exhibit even stronger spin-orbit coupling than the zincblende structure.Comment: 10 pages and 5 figure

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients

Uncovering the impact of DNA methyltransferase inhibitor treatment on the tumor microenvironment

Tumormikromiljøet er et komplekst økosystem bestående af kræftceller samt omgivende immunceller og stromale celler. Sammensætningen af disse celler samt deres funktionelle stadie kan afgøre hvordan en tumor udvikler sig og responderer på behandling. Dette har ført til forskning i at findebehandlinger, der kan ændre cellesammensætningen og funktionelle stadier af cellerne i tumormikromiljøet. En måde at opnå dette er ved brug af DNA methyltransferase hæmmere (DNMTi), som virker ved at hæmme de enzymer som normalt påsætter methylgrupper i DNA. DNMTi kan dermed omvende atypiske methyleringsmønstre i kræftceller, hvilket har vist sig at være nyttigt i kræftbehandling. DNMTi kan øge udtrykket og præsentationen af antigener på kræftcellernes overflade, hvilket gør at immunsystemet kan genkende dem. Derudover har DNMTi behandling også potentiale til at påvirke immuncellerne i tumormikromiljøet ved at øge aktiviteten af immunceller der kan dræbekræftcellerne og regulere immunsuppressive celler. DNMTi har haft god effekt i behandlingen af nogle typer af blodkræft, men kun begrænset effekt i behandling af solide tumorer. Mekanismerne bag virkningen af DNMTi mangler dog stadig en dybere forståelse. Formålet med mit projekt var at yderligere karakterisere hvordan DNMTi kan påvirke tumormikromiljøet på tværs af cellulære compartments. Til at undersøge dette brugte vi enkelt-celle mRNA-sekventering til at karakterisere ændringerne i tumormikromiljøet efter DNMTi behandling i musetumorer. Vi brugte to forskellige musetumorer, også at disse tumorer responderede forskelligt på behandlingen. Vores resultater indikerede, at DNMTi påvirkede immunceller i tumormikromiljøet, primært innate immunceller, samt påvirkede stromale celler ved at ændre sammensætningen af subtyper af cancer-associerede fibroblaster (CAFs). Vores resultater indikerede også at effekterne på tumormikromiljøet sker som følge af ændringer i kræftcellerne ved DNMTi behandlingen. Vi undersøgte også dynamiske ændringer i T celle receptor (TCR)repertoiret efter DNMTi behandling, hvor vi brugte en bilateral syngen tumor model til at undersøge dette. Vores resultater tydede dog på, at det primært er naturlige ændringer i TCR-repertoirerne der dominerer over ændringer induceret af DNMTi. Vi fandt også ud af, at DNTMi behandling måske også påvirker hvilke CAF subtyper der udvikles ved brug af et in vitro set-up. Da vi også så, at DNMTi behandling påvirkede CAFs i syngene tumorer kan dette tyde på, at DNMTi også virker ved at påvirke CAFs. Samlet set giver resultaterne der er præsenteret i denne afhandling yderligere indsigt i hvordan DNMTi behandling kan påvirke sammensætningen af tumormikromiljøet, og hvordan dette kan bruges i fremtidig brug af DNMTi som enkeltbehandling eller i kombination med andre behandlinger. The tumor microenvironment (TME) is a highly complex ecosystem composed of cancer cells as well as surrounding immune and stromal cells. The cellular composition and functional state of these components can determine whether a tumor progress and how it responds to treatments. This has prompted the exploration of treatments that can modify the composition and cellular states of the TME. One such strategy is epigenetic modulation using DNA methyltransferase inhibitors (DNMTi), which act by inhibiting the enzymes that catalyze the transfer of methyl groups to DNA. This can reverse aberrant methylation patterns in cancer, which can be utilized in anti-cancer treatment. DNMTi treatment have demonstrated to increase cancer immunogenicity, by increasing expression of tumor-associated antigens and major histocompatibility (MHC) molecules. Furthermore, DNMTis have shown potential to remodel immune cells within the TME by increasing the activity of antitumor immune cells and modulate immunosuppressive cells. DNMTis have shown success in the treatment of certain hematological malignancies, but the translation to solid tumors remains limited. However, the mechanisms underlying the effects of DNMTis remain poorly understood. The aim of my project was to further characterize how DNMTi remodel the TME across cellular compartments. We employed single-cell mRNA sequencing to characterize alterations in the TME of syngeneic mouse tumors following DNMTi treatment. We used two distinct syngeneic tumor models, and found that these tumors responded differently to DNMTi treatment. Our findings indicated that DNMTi remodeled the immune compartment, predominantly by engaging innate immune cells, and the cancer-associated fibroblast (CAF) compartment by altering the composition of CAF subtypes. Our findings further indicated that the remodeling of the TME may be linked to cancer cell-intrinsic alterations following DNMTi treatment. We also profiled dynamic changes of T cell receptor (TCR) repertoires following DNMTi treatment using a bilateral syngeneic tumor model. However, our findings indicated that tumor-intrinsic clonal dynamic changes might be dominating over DNMTiinduced alterations in TCR repertoires. We additionally found that DNMTi treatment may drive the formation of specific subtypes of CAFs using an in vitro set-up. Combined with the remodeling ofthe CAF compartment in syngeneic mouse tumors, our findings suggest a novel role of DNMTi in reprogramming CAFs. Collectively, the findings of this thesis provided further insights into the mechanisms of DNMTi in remodeling the TME and how this may direct future use of DNMTi as monotherapy or in combination therapies for the treatment of cancer.

HoloTile light engine:new digital holographic modalities and applications (Invited paper)

HoloTile is a patented computer generated holography approach with the aim of reducing the speckle noise caused by the overlap of the non-trivial physical extent of the point spread function in Fourier holographic systems from adjacent frequency components. By combining tiling of phase-only of rapidly generated sub-holograms with a PSF-shaping phase profile, each frequency component—or output ‘pixel’— in the Fourier domain is shaped to a desired non-overlapping profile. In this paper, we show the high-resolution, speckle-reduced reconstructions that can be achieved with HoloTile, as well as present new HoloTile modalities, including an expanded list of PSF options with new key properties. In addition, we discuss numerous applications for which HoloTile, its rapid hologram generation, and the new PSF options may be an ideal fit, including optical trapping and manipulation of particles, volumetric additive printing, information transfer and quantum communication.</p

HoloTile for Volumetric Additive Manufacturing (Invited)

HoloTile [1, 2, 3, 4] is a novel digital holographic light sculpting modality withproperties well suited to volumetric additive manufacturing (VAM). This paper discussesthe consequences of moving from an imaging-based to a holographic-based VAM configuration,and how HoloTile may be used to improve volumetric printing further

HoloTile for Volumetric Additive Manufacturing (Invited)

HoloTile [1, 2, 3, 4] is a novel digital holographic light sculpting modality withproperties well suited to volumetric additive manufacturing (VAM). This paper discussesthe consequences of moving from an imaging-based to a holographic-based VAM configuration,and how HoloTile may be used to improve volumetric printing further