University of Zurich

About: University of Zurich is a education organization based out in Zurich, Switzerland. It is known for research contribution in the topics: Population & Transplantation. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.

Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein

Abstract: PrPC is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPC. Mice homozygous for disrupted PrP genes have been generated. Surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. It is now feasible to determine whether mice devoid of PrPC can propagate prions and are susceptible to scrapie pathogenesis.

A tunable topological insulator in the spin helical Dirac transport regime

Abstract: Helical Dirac fermions—charge carriers that behave as massless relativistic particles with an intrinsic angular momentum (spin) locked to its translational momentum—are proposed to be the key to realizing fundamentally new phenomena in condensed matter physics. Prominent examples include the anomalous quantization of magneto-electric coupling, half-fermion states that are their own antiparticle, and charge fractionalization in a Bose– Einstein condensate, all of which are not possible with conventional Dirac fermions of the graphene variety. Helical Dirac fermions have so far remained elusive owing to the lack of necessary spin-sensitive measurements and because such fermions are forbidden to exist in conventional materials harbouring relativistic electrons, such as graphene or bismuth. It has recently been proposed that helical Dirac fermions may exist at the edges of certain types of topologically ordered insulators—materials with a bulk insulating gap of spin–orbit origin and surface states protected against scattering by time-reversal symmetry—and that their peculiar properties may be accessed provided the insulator is tuned into the so-called topological transport regime. However, helical Dirac fermions have not been observed in existing topological insulators. Here we report the realization and characterization of a tunable topological insulator in a bismuthbased class of material by combining spin-imaging and momentum-resolved spectroscopies, bulk charge compensation, Hall transport measurements and surface quantum control. Our results reveal a spin-momentum locked Dirac cone carrying a nontrivial Berry’s phase that is nearly 100 per cent spin-polarized, which exhibits a tunable topological fermion density in the vicinity of the Kramers point and can be driven to the long-sought topological spin transport regime. The observed topological nodal state is shown to be protected even up to 300 K. Our demonstration of room-temperature topological order and non-trivial spintexture in stoichiometric Bi_2Se_3.M_x (M_x indicates surface doping or gating control) paves the way for future graphene-like studies of topological insulators, and applications of the observed spinpolarized edge channels in spintronic and computing technologies possibly at room temperature.

The Environment and Directed Technical Change

Abstract: This paper introduces endogenous and directed technical change in a growth model with environmental constraints and limited resources. A unique final good is produced by combining inputs from two sectors. One of these sectors uses "dirty" machines and thus creates environmental degradation. Research can be directed to improving the technology of machines in either sector. We characterize dynamic tax policies that achieve sustainable growth or maximize intertemporal welfare, as a function of the degree of substitutability between clean and dirty inputs, environmental and resource stocks, and cross-country technological spillovers. We show that: (i) in the case where the inputs are sufficiently substitutable, sustainable long-run growth can be achieved with temporary taxation of dirty innovation and production; (ii) optimal policy involves both "carbon taxes" and research subsidies, so that excessive use of carbon taxes is avoided; (iii) delay in intervention is costly: the sooner and the stronger is the policy response, the shorter is the slow growth transition phase; (iv) the use of an exhaustible resource in dirty input production helps the switch to clean innovation under laissez-faire when the two inputs are substitutes. Under reasonable parameter values (corresponding to those used in existing models with exogenous technology) and with sufficient substitutability between inputs, it is optimal to redirect technical change towards clean technologies immediately and optimal environmental regulation need not reduce long-run growth. We also show that in a two-country extension, even though optimal environmental policy involves global policy coordination, when the two inputs are sufficiently substitutable environmental regulation only in the North may be sufficient to avoid a global disaster.

Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens

Abstract: The immune system influences the fate of developing cancers by not only functioning as a tumour promoter that facilitates cellular transformation, promotes tumour growth and sculpts tumour cell immunogenicity, but also as an extrinsic tumour suppressor that either destroys developing tumours or restrains their expansion. Yet, clinically apparent cancers still arise in immunocompetent individuals in part as a consequence of cancer-induced immunosuppression. In many individuals, immunosuppression is mediated by cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), two immunomodulatory receptors expressed on T cells. Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits-including durable responses--to patients with different malignancies. However, little is known about the identity of the tumour antigens that function as the targets of T cells activated by checkpoint blockade immunotherapy and whether these antigens can be used to generate vaccines that are highly tumour-specific. Here we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and we show that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Although mutant tumour-antigen-specific T cells are present in progressively growing tumours, they are reactivated following treatment with anti-PD-1 and/or anti-CTLA-4 and display some overlapping but mostly treatment-specific transcriptional profiles, rendering them capable of mediating tumour rejection. These results reveal that tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy, but they can also be used to develop personalized cancer-specific vaccines and to probe the mechanistic underpinnings of different checkpoint blockade treatments.