Interlayer exciton laser of extended spatial coherence in atomically thin heterostructures.

Two-dimensional semiconductors have emerged as a new class of materials for nanophotonics owing to their strong exciton-photon interaction1,2 and their ability to be engineered and integrated into devices3. Here we take advantage of these properties to engineer an efficient lasing medium based on direct-bandgap interlayer excitons in rotationally aligned atomically thin heterostructures4. Lasing is measured from a transition-metal dichalcogenide heterobilayer (WSe2-MoSe2) integrated in a silicon nitride grating resonator. An abrupt increase in the spatial coherence of the emission is observed across the lasing threshold. The work establishes interlayer excitons in two-dimensional heterostructures as a gain medium with spatially coherent lasing emission and potential for heterogeneous integration. With electrically tunable exciton-photon interaction strengths5 and long-range dipolar interactions, these interlayer excitons are promising for application as low-power, ultrafast lasers and modulators and for the study of many-body quantum phenomena6.

Emergence of correlations in alternating twist quadrilayer graphene.

Alternating twist multilayer graphene (ATMG) has recently emerged as a family of moiré systems that share several fundamental properties with twisted bilayer graphene, and are expected to host similarly strong electron-electron interactions near the magic angle. Here, we study alternating twist quadrilayer graphene (ATQG) samples with twist angles of 1.96° and 1.52°, which are slightly removed from the magic angle of 1.68°. At the larger angle, we find signatures of correlated insulators only when the ATQG is hole doped, and no signatures of superconductivity, and for the smaller angle we find evidence of superconductivity, while signs of the correlated insulators weaken. Our results provide insight into the twist angle dependence of correlated phases in ATMG and shed light on the nature of correlations in the intermediate coupling regime at the edge of the magic angle range where dispersion and interaction are of the same order.

Emergence of Interlayer Coherence in Twist-Controlled Graphene Double Layers.

We report enhanced interlayer tunneling with reduced linewidth at zero interlayer bias in a twist-controlled double monolayer graphene heterostructure in the quantum Hall regime, when the top (ν_{T}) and bottom (ν_{B}) layer filling factors are near ν_{T}=±1/2,±3/2 and ν_{B}=±1/2,±3/2, and the total filling factor ν=±1 or ±3. The zero-bias interlayer conductance peaks are stable against variations of layer filling factor, and signal the emergence of interlayer phase coherence. Our results highlight twist control as a key attribute in revealing interlayer coherence using tunneling.

Quantum Lifetime Spectroscopy and Magnetotunneling in Double Bilayer Graphene Heterostructures.

We describe a tunneling spectroscopy technique in a double bilayer graphene heterostructure where momentum-conserving tunneling between different energy bands serves as an energy filter for the tunneling carriers, and allows a measurement of the quasiparticle state broadening at well-defined energies. The broadening increases linearly with the excited state energy with respect to the Fermi level and is weakly dependent on temperature. In-plane magnetotunneling reveals a high degree of rotational alignment between the graphene bilayers, and an absence of momentum randomizing processes.

Correlated Insulating States in Twisted Double Bilayer Graphene.

We present a combined experimental and theoretical study of twisted double bilayer graphene with twist angles between 1° and 1.35°. Consistent with moiré band structure calculations, we observe insulators at integer moiré band fillings one and three, but not two. An applied transverse electric field separates the first moiré conduction band from neighboring bands, and favors the appearance of correlated insulators at 1/4, 1/2, and 3/4 band filling. Insulating states at 1/4 and 3/4 band filling emerge only in a parallel magnetic field (B_{||}), whereas the resistivity at half band filling is weakly dependent on B_{||}. Our findings suggest that correlated insulators are favored when a moiré flat band is spectrally isolated, and are consistent with a mean-field picture in which insulating states are established by breaking both spin and valley symmetries at 1/4 and 3/4 band filling and valley polarization alone at 1/2 band filling.

Spin-Conserving Resonant Tunneling in Twist-Controlled WSe2-hBN-WSe2 Heterostructures.

We investigate interlayer tunneling in heterostructures consisting of two tungsten diselenide (WSe2) monolayers with controlled rotational alignment, and separated by hexagonal boron nitride. In samples where the two WSe2 monolayers are rotationally aligned we observe resonant tunneling, manifested by a large conductance and negative differential resistance in the vicinity of zero interlayer bias, which stem from energy- and momentum-conserving tunneling. Because the spin-orbit coupling leads to coupled spin-valley degrees of freedom, the twist between the two WSe2 monolayers allows us to probe the conservation of spin-valley degree of freedom in tunneling. In heterostructures where the two WSe2 monolayers have a 180° relative twist, such that the Brillouin zone of one layer is aligned with the time-reversed Brillouin zone of the opposite layer, the resonant tunneling between the layers is suppressed. These findings provide evidence that, in addition to momentum, the spin-valley degree of freedom is also conserved in vertical transport.

Strongly Enhanced Tunneling at Total Charge Neutrality in Double-Bilayer Graphene-WSe_{2} Heterostructures.

We report the experimental observation of strongly enhanced tunneling between graphene bilayers through a WSe_{2} barrier when the graphene bilayers are populated with carriers of opposite polarity and equal density. The enhanced tunneling increases sharply in strength with decreasing temperature, and the tunneling current exhibits a vertical onset as a function of interlayer voltage at a temperature of 1.5 K. The strongly enhanced tunneling at overall neutrality departs markedly from single-particle model calculations that otherwise match the measured tunneling current-voltage characteristics well, and suggests the emergence of a many-body state with condensed interbilayer excitons when electrons and holes of equal densities populate the two layers.

Coherent Interlayer Tunneling and Negative Differential Resistance with High Current Density in Double Bilayer Graphene-WSe2 Heterostructures.

We demonstrate gate-tunable resonant tunneling and negative differential resistance between two rotationally aligned bilayer graphene sheets separated by bilayer WSe2. We observe large interlayer current densities of 2 and 2.5 µA/µm2 and peak-to-valley ratios approaching 4 and 6 at room temperature and 1.5 K, respectively, values that are comparable to epitaxially grown resonant tunneling heterostructures. An excellent agreement between theoretical calculations using a Lorentzian spectral function for the two-dimensional (2D) quasiparticle states, and the experimental data indicates that the interlayer current stems primarily from energy and in-plane momentum conserving 2D-2D tunneling, with minimal contributions from inelastic or non-momentum-conserving tunneling. We demonstrate narrow tunneling resonances with intrinsic half-widths of 4 and 6 meV at 1.5 and 300 K, respectively.

[The age of Gutenberg is over: a consideration of medical education--past, present and future]. / Gutenberg war gestern: Ein Beitrag zur Ausbildung in der Medizin gestern, heute und morgen.

Education is the basis for reliable medical care and medical progress. Our medical knowledge has increased more in the past 50 years than in the 500 years before. The spatial and human resource capacity of our universities cannot cope with the existing academic structures and needs. Part of the problem can be solved by "blended learning", that is a combination of traditional teaching methods (frontal lectures, courses, bedside teaching) with supplementary web-based e-learning. In addition to conveying a sound basic knowledge, the ability to cope with modern media and prepare for lifelong learning must also be taught. Out of the large number of e-learning platforms for undergraduate students offered in the internet, we present the program DOIT (Dermatology Online with Interactive Technology; http://www.swisdom.org) and the program Dermokrates (http://www.Dermokrates.com) of the German, Austrian and Swiss Dermatological Societies for postgraduate Continuing Medical Education (CME). The biggest obstacle in the implementation of new developments is the stubborn adherence to traditional structures.

History of sexually transmitted infections (STI).

Sexually transmitted diseases (STD) are as old as mankind and epidemics are mentioned already in the Old Testament. However, the perception of the conditions has changed over the centuries. In ancient times they were taken for an individual punishment for a blasphemic conduct of life or as a consequence of low sanitation and hygiene. In the medieval ages, the relation to sexual activities was recognized, but the diversity of clinical symptoms was seen as variations of one disease, depending on the stage of the disease and the general health condition of the diseased person. In the late 15th and 16th century a presumably "new plague" had been imported to Europe and was rapidly spread by soldiers. Misinterpretations of wrong experiments on the suspected identity of syphilis and gonorrhoea led to nosologic misconceptions in the 17th and early 19th century. The late 19th and beginning of 20st century due to the many achievements in microbiology and chemistry finally took the frightening threat from the STDs, which have terrorized millions of "normal" and "famous" people of all social classes over centuries and has been linked to many scandals. Moreover, the perception of STDs has turned from a "personal stroke of fate" into a collectively important issue of public health.

Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.

Melanoma is the main cause of death in patients with skin cancer. Cytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restricted and tumor antigen-specific manner. Several melanoma-associated tumor antigens have been identified. These antigens are suitable candidates for a vaccination therapy of melanoma. Dendritic cells (DCs) are antigen-presenting cells (APCs) specialized for the induction of a primary T-cell response. Mouse studies have demonstrated the potent capacity of DCs to induce antitumor immunity. In the present clinical pilot study, DCs were generated in the presence of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) and were pulsed with tumor lysate or a cocktail of peptides known to be recognized by CTLs, depending on the patient's HLA haplotype. Keyhole limpet hemocyanin (KLH) was added as a CD4 helper antigen and immunological tracer molecule. Sixteen patients with advanced melanoma were immunized on an outpatient basis. Vaccination was well tolerated. No physical sign of autoimmunity was detected in any of the patients. DC vaccination induced delayed-type hypersensitivity (DTH) reactivity toward KLH in all patients, as well as a positive DTH reaction to peptide-pulsed DCs in 11 patients. Recruitment of peptide-specific CTLs to the DTH challenge site was also demonstrated. Therefore, antigen-specific immunity was induced during DC vaccination. Objective responses were evident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (skin, soft tissue, lung, pancreas) and one additional minor response. These data indicate that vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma. Further studies are necessary to demonstrate clinical effectiveness and impact on the survival of melanoma patients.

The sebaceous nevus: a nevus with deletions of the PTCH gene.

Sebaceous nevi (SN) are congenital malformations of the skin with the potential to develop into basal cell carcinoma (BCC). To date, the molecular basis for their carcinogenic potential remains unknown. The genetic defect in BCC is known and involves the human homologue of Drosophila patched (PTCH) on chromosome 9q22.3. The objective of this study was to test whether allelic deletion of the PTCH gene could already be detected in SN. Twenty-one paraffin-embedded SN were investigated in this study. Basaloid cells in conjunction with mature sebaceous glands as well as epidermal layer apart from SN were microdissected and subjected to single-step DNA extraction. We performed the analysis with polymorphic markers at 9q22.3 (D9S15, D9S252, D9S287, and D9S303). Of the 20 informative SN, 8 (40%) exhibited loss of heterozygosity at least at one locus. Here, we provide the first evidence of the involvement of the tumor suppressor gene PTCH in SN. Whether PTCH deletion in SN is associated with progression to BCC and/or other appendageal tumors should be addressed in future studies.

Coexpression of CD40 and CD40 ligand in cutaneous T-cell lymphoma (mycosis fungoides).

Microarray analysis is a promising new approach for creating specific expression profiles of multiple genes simultaneously. We quantitatively analyzed differential gene expression patterns in mycosis fungoides-derived clonal T cells and autologous, identically cultured CD4+ lymphocytes using microarrays containing 588 cDNA segments from genes relevant to cell signaling, carcinogenesis, and apoptosis. Among other dissimilarities, neoplastic T cells showed coexpression of CD40 (Bp50) and CD40 ligand (gp39, CD154). These results could be corroborated by reverse transcription-PCR, immunohistochemistry, and two-color immunofluorescence staining. Our data suggest that in cutaneous T-cell lymphoma, CD40/CD40 ligand interactions might represent a paracrine loop that is crucial not only in preventing apoptosis or positively regulating growth but also in homing of neoplastic cells to the skin.

Prognostic value of serum 5-S-cysteinyldopa for monitoring human metastatic melanoma during immunochemotherapy.

The melanin metabolite 5-S-cysteinyldopa (5-S-CD) has been reported to be helpful in detecting occult melanoma metastases and as a prognostic marker in B16 melanoma-bearing mice. The goal of our study was to analyze the significance of the serum 5-S-CD level for the biochemical detection of metastases in human malignant melanoma (MM) and for monitoring the progression or the immunochemotherapeutically induced regression of MM. From 11 patients with metastatic MM observed between 1991 and 1995, serum samples were collected before and after each cycle of immunotherapy or immunochemotherapy. Samples were analyzed for 5-S-CD by automated high performance liquid chromatography with electrochemical detection. Cycles of immunochemotherapy consisted of human interleukin 2 and IFN-alpha (four patients) or of human interleukin 2, IFN-alpha, and dacarbazine (seven patients). Serum value of 5-S-CD in our normal controls was 1.9 +/- 0.6 ng/ml. All patients with metastatic MM showed 5-S-CD serum levels above the upper normal limit of 3.2 ng/ml (10 nM) and ranged from 2.3-fold (4.3 +/- 3.9 ng/ml) of the normal control values in early stages of metastases to more than 50-fold (94.3 +/- 220.3 ng/ml) of the normal control values in advanced stages of the disease. In 28 of 41 (68%) immunochemotherapeutical cycles, a decrease of 5-S-CD was seen during therapy, and in 13 cycles (31.7%), an increase was seen. Patients with more than 68% decreasing cycles (defined as responders; n = 5) showed significantly longer survival times (P = 0.008) than patients with less than 68% decreasing cycles (nonresponders; n = 6). High levels of 5-S-CD were also observed in metastasizing amelanotic melanoma. Serum 5-S-CD is a useful marker for monitoring the clinical course of MM patients, for discriminating between responders and nonresponders to immunochemotherapy, and as a prognostic factor concerning survival time and death risk.

Circulating intercellular adhesion molecule-1 in melanoma patients: induction by interleukin-2 therapy.

Intercellular adhesion molecule-1 (ICAM-1, CD54), a molecule bound to the cell surface membrane, mediates various cell-cell interactions in inflammation and immunosurveillance. By means of a new specific enzyme-linked immunosorbent assay (ELISA) for soluble ICAM-1, free circulating ICAM-1 was measured in serum from five healthy volunteers, 10 melanoma patients at different stages of their disease, and eight patients receiving high-dose interleukin-2 (IL-2) for metastatic melanoma. No correlation between the concentration of circulating ICAM-1 and the tumor burden could be detected. In melanoma patients receiving high-dose IL-2, we observed an increase of circulating ICAM-1 of up to 200%, compared to the concentration prior to therapy, ranging between 4 and 13 ng/ml. The increase in circulating ICAM-1 was associated with the induction of tumor necrosis factor-alpha and interferon-gamma.

Effects of chronic intracutaneous administration of arachidonic acid and its metabolites. Induction of leukocytoclastic vasculitis by leukotriene B4 and 12-hydroxyeicosatetraenoic acid and its prevention by prostaglandin E2.

Despite the postulated role of arachidonic acid-derived metabolites in the pathophysiology of chronic inflammatory dermatoses such as psoriasis and atopic or contact dermatitis, the cutaneous effects of their chronic application have not yet been investigated. We therefore studied systematically the effects of chronic intracutaneous administration of arachidonic acid, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 12-hydroxyeicosatetraenoic acid (12-HETE) in guinea pigs, and describe previously unrecognized findings partly different from those reported in the past for short-term or topical application of these inflammatory mediators. Leukotriene B4 and 12-HETE led to massive histologic changes characteristic of leukocytoclastic vasculitis. These changes could be prevented by concomitant PGE2 administration. In epidermis, LTB4 and 12-HETE caused some spongiosis as well as hyperplasia and increased tritiated thymidine autoradiographic labeling index. Arachidonic acid and PGE2 alone had little effect. These data suggest that in addition to other inflammatory or hyperproliferative dermatoses, arachidonic acid metabolites formed via lipoxygenase pathways could play a major role in leukocytoclastic vasculitis, whereas PGs could exert a tissue-protective effect.