Conduction spectroscopy of a proximity induced superconducting topological insulator

The combination of superconductivity and the helical spin-momentum locking at the surface state of a topological insulator (TI) has been predicted to give rise to p-wave superconductivity and Majorana bound states. The superconductivity can be induced by the proximity effect of a an s-wave superconductor (S) into the TI. To probe the superconducting correlations inside the TI, dI/dV spectroscopy has been performed across such S-TI interfaces. Both the alloyed Bi$_{1.5}$Sb$_{0.5}$Te$_{1.7}$Se$_{1.3}$ and the stoichiometric BiSbTeSe$_2$ have been used as three dimensional TI. In the case of Bi$_{1.5}$Sb$_{0.5}$Te$_{1.7}$Se$_{1.3}$, the presence of disorder induced electron-electron interactions can give rise to an additional zero-bias resistance peak. For the stoichiometric BiSbTeSe$_2$ with less disorder, tunnel barriers were employed in order to enhance the signal from the interface. The general observations in the spectra of a large variety of samples are conductance dips at the induced gap voltage, combined with an increased sub-gap conductance, consistent with p-wave predictions. The induced gap voltage is typically smaller than the gap of the Nb superconducting electrode, especially in the presence of an intentional tunnel barrier. Additional uncovered spectroscopic features are oscillations that are linearly spaced in energy, as well as a possible second order parameter component.Comment: Semiconductor Science and Technology; Special Issue on Hybrid Quantum Materials and Device

Probing resonating valence bonds on a programmable germanium quantum simulator

Simulations using highly tunable quantum systems may enable investigations of condensed matter systems beyond the capabilities of classical computers. Quantum dots and donors in semiconductor technology define a natural approach to implement quantum simulation. Several material platforms have been used to study interacting charge states, while gallium arsenide has also been used to investigate spin evolution. However, decoherence remains a key challenge in simulating coherent quantum dynamics. Here, we introduce quantum simulation using hole spins in germanium quantum dots. We demonstrate extensive and coherent control enabling the tuning of multi-spin states in isolated, paired, and fully coupled quantum dots. We then focus on the simulation of resonating valence bonds and measure the evolution between singlet product states which remains coherent over many periods. Finally, we realize four-spin states with $s$-wave and $d$-wave symmetry. These results provide means to perform non-trivial and coherent simulations of correlated electron systems.Comment: Article main text and Supplementary Information Main text: 9 pages, 5 figures Supplementary Information: 15 pages, 9 figure

Single-hole pump in germanium

Abstract: Single-charge pumps are the main candidates for quantum-based standards of the unit ampere because they can generate accurate and quantized electric currents. In order to approach the metrological requirements in terms of both accuracy and speed of operation, in the past decade there has been a focus on semiconductor-based devices. The use of a variety of semiconductor materials enables the universality of charge pump devices to be tested, a highly desirable demonstration for metrology, with GaAs and Si pumps at the forefront of these tests. Here, we show that pumping can be achieved in a yet unexplored semiconductor, i.e. germanium. We realise a single-hole pump with a tunable-barrier quantum dot electrostatically defined at a Ge/SiGe heterostructure interface. We observe quantized current plateaux by driving the system with a single sinusoidal drive up to a frequency of 100 MHz. The operation of the prototype was affected by accidental formation of multiple dots, probably due to disorder potential, and random charge fluctuations. We suggest straightforward refinements of the fabrication process to improve pump characteristics in future experiments

Capacitive crosstalk in gate-based dispersive sensing of spin qubits

In gate-based dispersive sensing, the response of a resonator attached to a quantum dot gate is detected by a reflected radio-frequency signal. This enables fast readout of spin qubits and tune up of arrays of quantum dots, but comes at the expense of increased susceptibility to crosstalk, as the resonator can amplify spurious signals and induce fluctuations in the quantum dot potential. We attach tank circuits with superconducting NbN inductors and internal quality factors $Q_{\mathrm{i}}$>1000 to the interdot barrier gate of silicon double quantum dot devices. Measuring the interdot transition in transport, we quantify radio-frequency crosstalk that results in a ring-up of the resonator when neighbouring plunger gates are driven with frequency components matching the resonator frequency. This effect complicates qubit operation and scales with the loaded quality factor of the resonator, the mutual capacitance between device gate electrodes, and with the inverse of the parasitic capacitance to ground. Setting qubit frequencies below the resonator frequency is expected to substantially suppress this type of crosstalk.Comment: 7 pages, 4 figures, supplementary informatio

Electrical operation of planar Ge hole spin qubits in an in-plane magnetic field

In this work we present a comprehensive theory of spin physics in planar Ge hole quantum dots in an in-plane magnetic field, where the orbital terms play a dominant role in qubit physics, and provide a brief comparison with experimental measurements of the angular dependence of electrically driven spin resonance. We focus the theoretical analysis on electrical spin operation, phonon-induced relaxation, and the existence of coherence sweet spots. We find that the choice of magnetic field orientation makes a substantial difference for the properties of hole spin qubits. Furthermore, although the Schrieffer-Wolff approximation can describe electron dipole spin resonance (EDSR), it does not capture the fundamental spin dynamics underlying qubit coherence. Specifically, we find that: (i) EDSR for in-plane magnetic fields varies non-linearly with the field strength and weaker than for perpendicular magnetic fields; (ii) The EDSR Rabi frequency is maximized when the a.c. electric field is aligned parallel to the magnetic field, and vanishes when the two are perpendicular; (iii) The Rabi ratio $T_1/T_\pi$, i.e. the number of EDSR gate operation per unit relaxation time, is expected to be as large as $5{\times}10^5$ at the magnetic fields used experimentally; (iv) The orbital magnetic field terms make the in-plane $g$-factor strongly anisotropic in a squeezed dot, in excellent agreement with experimental measurements; (v) The coherence sweet spots do not exist in an in-plane magnetic field, as the orbital magnetic field terms expose the qubit to all components of the defect electric field. These findings will provide a guideline for experiments to design ultrafast, highly coherent hole spin qubits in Ge

Electrical control of uniformity in quantum dot devices

Highly uniform quantum systems are essential for the practical implementation of scalable quantum processors. While quantum dot spin qubits based on semiconductor technology are a promising platform for large-scale quantum computing, their small size makes them particularly sensitive to their local environment. Here, we present a method to electrically obtain a high degree of uniformity in the intrinsic potential landscape using hysteretic shifts of the gate voltage characteristics. We demonstrate the tuning of pinch-off voltages in quantum dot devices over hundreds of millivolts that then remain stable at least for hours. Applying our method, we homogenize the pinch-off voltages of the plunger gates in a linear array for four quantum dots reducing the spread in pinch-off voltage by one order of magnitude. This work provides a new tool for the tuning of quantum dot devices and offers new perspectives for the implementation of scalable spin qubit arrays

Nanoscale Mapping of the 3D Strain Tensor in a Germanium Quantum Well Hosting a Functional Spin Qubit Device

A strained Ge quantum well, grown on a SiGe/Si virtual substrate and hosting two electrostatically defined hole spin qubits, is nondestructively investigated by synchrotron-based scanning X-ray diffraction microscopy to determine all its Bravais lattice parameters. This allows rendering the three-dimensional spatial dependence of the six strain tensor components with a lateral resolution of approximately 50 nm. Two different spatial scales governing the strain field fluctuations in proximity of the qubits are observed at 1 μm, respectively. The short-ranged fluctuations have a typical bandwidth of 2 × 10-4 and can be quantitatively linked to the compressive stressing action of the metal electrodes defining the qubits. By finite element mechanical simulations, it is estimated that this strain fluctuation is increased up to 6 × 10-4 at cryogenic temperature. The longer-ranged fluctuations are of the 10-3 order and are associated with misfit dislocations in the plastically relaxed virtual substrate. From this, energy variations of the light and heavy-hole energy maxima of the order of several 100 μeV and 1 meV are calculated for electrodes and dislocations, respectively. These insights over material-related inhomogeneities may feed into further modeling for optimization and design of large-scale quantum processors manufactured using the mainstream Si-based microelectronics technology

Ubiquitin Fold Modifier 1 (UFM1) and Its Target UFBP1 Protect Pancreatic Beta Cells from ER Stress-Induced Apoptosis

UFM1 is a member of the ubiquitin like protein family. While the enzymatic cascade of UFM1 conjugation has been elucidated in recent years, the biological function remains largely unknown. In this report we demonstrate that the recently identified C20orf116 [1], which we name UFM1-binding protein 1 containing a PCI domain (UFBP1), andCDK5RAP3 interact with UFM1. Components of the UFM1 conjugation pathway (UFM1, UFBP1, UFL1 and CDK5RAP3) are highly expressed in pancreatic islets of Langerhans and some other secretory tissues. Co-localization of UFM1 with UFBP1 in the endoplasmic reticulum (ER)depends on UFBP1. We demonstrate that ER stress, which is common in secretory cells, induces expression of Ufm1, Ufbp1 and Ufl1 in the beta-cell line INS-1E.siRNA-mediated Ufm1 or Ufbp1knockdown enhances apoptosis upon ER stress.Silencing the E3 enzyme UFL1, results in similar outcomes, suggesting that UFM1-UFBP1 conjugation is required to prevent ER stress-induced apoptosis. Together, our data suggest that UFM1-UFBP1participate in preventing ER stress-induced apoptosis in protein secretory cells

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Mechanism and role of COX-2 up-regulation by photodynamic therapy.

Fotodynamische therapie (PDT) is een erkende, minimaal invasieve therape utische aanpak voor de behandeling van verschillende tumoren en sommige goedaardige gezwellen. PDT is gebaseerd op het gecombineerd gebrui k van een licht absorberende stof (fotosensibilisator), die preferentiee l accumuleert in maligne tumoraal weefsel, en de bestraling met zichtbaa r licht van een golflengte die overeenkomt met het absorptiespectrum van de fotosensibilisator. Dit belichtingsproces leidt in de aanwezig heid van moleculaire zuurstof tot de ontwikkeling van reactieve zuurstof moleculen wat tenslotte resulteert in celdood. Bijgevolg staat PD T een tweezijdige specificiteit toe daar de simultane aanwezigheid van z owel de fotosensibilisator als licht noodzakelijk is. Hypericine, een polycyclische aromatische verbinding die behoort tot de chemische klasse van de fenantroperyleenchinonen, is een natuurlijk voor komende fotosensibilisator aanwezig in Hypericum perforatum, beter gekend als St.-Janskruid. Zijn fotochemische en -fysische eigensc happen samen met het feit dat hypericine in het donker noch toxisch, noc h genotoxisch is, maken van deze fotosensibilisator een beloftevol midde l in PDT. Voorafgaande studies met humane kankercellen hebben reed s aangetoond dat PDT met hypericine apoptose of necrose induceert, afhan kelijk van de gebruikte concentratie en licht dosis. In een experi menteel diermodel leidde hypericine PDT van een blaaskanker cel tot een dramatische vermindering van het groeipotentieel van de tumorcellen, maa r heropleving van de tumor kan optreden. Daarom werd deze studie o pgezet met als doel om op moleculair niveau de mogelijke targets op te s poren die deze adaptieve respons van de kankercel op hypericine PDT regu leren. In dit werk werd duidelijk aangetoond dat zowel hypericine als pyropheop horbide-a methyl ester (PPME) gebaseerde PDT van humane kankercellen, le idt tot een verhoogde expressie van het induceerbare cyclooxygenase-2 (C OX-2) enzym en een daarmee samengaande secretie van prostaglandine E2 (P GE2). De signaalwegen en het mechanisme die verantwoordelijk zijn voor deze COX-2 inductie blijken fotosensibilisator specifiek te zijn.&amp;n bsp; Het uitdiepen van de signaalwegen legde bloot dat het p38 MAPK een belangrijke rol speelt in de door hypericine PDT geïnduceerde overexpres sie van COX-2. Het blokkeren van deze signaalweg met behulp van ee n farmacologische remmer van het p38 MAPK (PD169316), verhinderde de PDT geïnduceerde COX-2 expressie volledig, en dit effect kon worden omgekee rd door de overexpressie van een drugresistente mutant van het p38 MAPK. Bovendien vertoonde p38a MAPK knock-out MEFs een gebrekkige COX-2 inductie na hypericine PDT. Verdere ontleding van deze signaalweg toonde aan dat de COX-2 expressie in antwoord op hypericine PDT afhanke lijk is van de selectieve activering van het p38 MAPK substraat MAPK gea ctiveerd proteïnekinase-2 (MK2). Het mechanisme dat verantwoordeli jk is voor de PDT geïnduceerde COX-2 mRNA en proteïne niveaus heeft geen betrekking tot NF-kB activering. Meer nog, dit inductieproces is onafhankelijk van de transcriptionele activering van de cox-2 genp romoter. Uit de studie van de halfwaardetijd van het COX-2 mRNA bl ijkt dat het p38 MAPK zijn effect hoofdzakelijk uitoefent via de stabili sering van het COX-2 transcript. Bijgevolg duiden deze data op de betrokkenheid van een door p38 MAPK-MK2 tot stand gebrachte stabiliserin g van het COX-2 transcript na hypericine PDT. In tegenstelling, PP ME PDT induceert de transcriptionele activering van de cox-2 genpr omoter en deze activering kan worden verhinderd door het gebruik van een IKK antagonist (BAY117085). Bovendien waren Hela cellen, die de N F-kB super-repressor IkBa (S32-36A) tot expressie brengen, aangetast in hun PDT geïnduceerde COX-2 expressie, wat duidelijk het belang van de IK K-IkBa-NF-kB weg in deze PDT respons aantoont. In een tweede deel van deze studie hebben we de functionele rol van deze COX-2 regulatie bestudeerd in de PDT geïnduceerde cellulaire respons.&amp;n bsp; We ontdekten dat vrij arachidonzuur (AA), dat na hypericine PDT vri jgesteld wordt uit de membraan fosfolipiden door PLA2 activiteit, zou ku nnen functioneren als een belangrijke regelaar in het bepalen van de cel dood/overlevingsbalans na PDT. Aan de ene kant functioneert AA als een dood boodschapper , en aan de andere kant draagt het bij tot de ac tivering van de p38 MAPK-COX-2 cascade. Dus, overexpressie van COX -2 fungeert als een intracellulaire gootsteen voor niet veresterd AA e n bevordert de productie van PGE2. Hoewel we konden aantonen dat h et blokkeren van de p38 MAPK activiteit de apoptotische respons na PDT v ersterkt, was dit niet het geval voor de inhibitie van COX-2 activiteit. Het is bijgevolg onwaarschijnlijk dat COX-2 de stroomafwaartse me diator voorstelt van de p38 MAPK signaalcascade die een negatieve invloe d heeft op de aanvang van het apoptotische proces in PDT beschadigde cel len. Hoe dan ook, een belangrijk rol kan toegeschreven worden voor de p38 MAPK-COX-2 cascade in het proces van neo-angiogenese, daar PDT g eïnduceerde PGE2 en VEGF secretie endotheelcel migratie veroorzaakt, een essentiële stap in angiogenese. Hoewel endotheelcel migratie in d ezelfde mate wordt verhinderd door de COX-2 remmer NS398, is de inhibiti e van de p38 MAPK signaalweg efficiënter in het blokkeren van VEGF synth ese. Samenvattend blijkt de inhibitie van de p38 MAPK signaalweg m eer belovend te zijn als een nieuwe behandelingsstrategie voor hypericin e PDT vergeleken met het gebruik van COX-2 remmers, daar het alle COX-2 afhankelijke fenotypes zou kunnen omvatten. Alles bij elkaar moedi gen deze resultaten aan tot verdere in vivo studies om het anti-an giogene en pro-apoptotische potentieel te bepalen van hypericine PDT van tumoren gecombineerd met de farmacologische inhibitie van p38 MAPK.Chapter 1. General introduction 1. Photodynamic therapy 1.1. PDT in medicine: a historical perspective 1.2. Mechanism of action 1.3. Photosensitizers 2. Cell fate after photodynamic therapy 2.1. Brief introduction to apoptosis 2.2. Cell death pathways in PDT 2.3. Signaling pathways in PDT 3. Cyclooxygenase-2 3.1. Cyclooxygenase isozymes 3.2. Mechanisms of catalysis and inhibition 3.3. Regulation of expression 3.4. COX-2 in cancer and in response to drug therapy Chapter 2. Aims and outline of the study Chapter 3. Materilas and methods 1. Materials 2. Experimental procedures 2.1. Cell culture 2.2. Cell photosensitization 2.3. Preparation of cell extracts and Western blotting 2.4. Caspase assay 2.5. Immunoprecipitation and protein kinase assay 2.6. Asessment of cell viability 2.7. Cell death assay 2.8. Transient transfections 2.9. Luciferase reporter assay 2.10. Cell cycle analysis 2.11. Electrophoretic mobility shift assay (EMSA) 2.12. (Ca²+ )cyt measurements with Indo-1 2.13. Arachidonic acid release 2.14. PGE2 and VEGF measurement 2.15. RT-PCR 2.16. RNA stability assay 2.17. Endothelial cell migration Chapter 4. Signaling pathways mediating the up-regulation of cyclooxygenase-2 in PDT-treated cancer cells 1. Introduction 2. Results 2.1. Hypericin-mediated PDT of cancer cells leads to up-regulation of COX-2 2.2. Cyclooxygenase-2 is up-regulated by the restricted activation of p38 MAPK 2.3. NF-κB is not involved in the up-regulation of COX-2 by hypericin-PDT 2.4. COX-2 mRNA is stabilized by p38 MAPK in hypericin-PDT treated cells 2.5. The mechanisms of COX-2 up-regulation by PDT are photosensitizer specific 2.6. The cox-2 gene is transcriptionally regulated upon PPME-PDT Chapter 5. On the role of p38 MAPK-COX-2 cascade in hypericin-based PDT 1. Introduction 2. Results 2.1. PDT induces rapid rise in (Ca²+)cyt and cPLA2 generated arachidonic acid release 2.2. PLA2-generated arachidonic acid contributes to apoptosis and to p38 MAPK activation following hypericin-PDT 2.3. p38α supports survival after PDT injury 2.4. The COX-2 antagonist NS398 does not significantly sensitize cells to PDT-induced apoptosis 2.5. Inhibition of p38 MAPK abolishes PGE2 and VEGF release 2.6. Targeted p38 MAPK inhibition suppresses tumor-associated endothelial cell migration Chapter 6. General discussion and perspectives 1. Signaling pathways mediating the up-regulation of cyclooxygenase-2 in PDT treated cells 2. On the role of p38 MAPK-COX-2 cescade in PDT Summary Samenvatting Referencesstatus: publishe