Large-Area Epitaxial Mott Insulating 1T-TaSe2 Monolayer on GaP(111)B.

Two-dimensional Mott materials have recently been reported in the dichalcogenide family with high potential for Mottronic applications. Nevertheless, their widespread use as a single or few layers is hampered by their limited device integration resulting from their growth on graphene, a metallic substrate. Here, we report on the fabrication of 1T-TaSe2 monolayers grown by molecular beam epitaxy on semiconducting gallium phosphide substrates. At the nanoscale, the charge density wave reconstruction and a moiré pattern resulting from the monolayer interaction with the substrate are observed by scanning tunneling microscopy. The fully open gap unveiled by tunneling spectroscopy, which can be further manipulated by the proximity of a metal tip, is confirmed by transport measurements from micrometric to millimetric scales, demonstrating a robust Mott insulating phase at up to 400 K.

How a dc Electric Field Drives Mott Insulators Out of Equilibrium.

Out of equilibrium phenomena are a major issue of modern physics. In particular, correlated materials such as Mott insulators experience fascinating long-lived exotic states under a strong electric field. Yet, the origin of their destabilization by the electric field is not elucidated. Here we present a comprehensive study of the electrical response of canonical Mott insulators GaM_{4}Q_{8} (M=V, Nb, Ta, Mo; Q=S, Se) in the context of a microscopic theory of electrical breakdown where in-gap states allow for a description in terms of a two-temperature model. Our results show how the nonlinearities and the resistive transition originate from a massive creation of hot electrons under an electric field. These results give new insights for the control of the long-lived states reached under an electric field in these systems which has recently open the way to new functionalities used in neuromorphic applications.

Evidence of a nonequilibrium distribution of quasiparticles in the microwave response of a superconducting aluminum resonator.

In a superconductor, absorption of photons with an energy below the superconducting gap leads to redistribution of quasiparticles over energy and thus induces a strong nonequilibrium quasiparticle energy distribution. We have measured the electrodynamic response, quality factor, and resonant frequency of a superconducting aluminium microwave resonator as a function of microwave power and temperature. Below 200 mK, both the quality factor and resonant frequency decrease with increasing microwave power, consistent with the creation of excess quasiparticles due to microwave absorption. Counterintuitively, above 200 mK, the quality factor and resonant frequency increase with increasing power. We demonstrate that the effect can only be understood by a nonthermal quasiparticle distribution.

Dynamics and gravitational wave signature of collapsar formation.

We perform 3+1 general relativistic simulations of rotating core collapse in the context of the collapsar model for long gamma-ray bursts. We employ a realistic progenitor, rotation based on results of stellar evolution calculations, and a simplified equation of state. Our simulations track self-consistently collapse, bounce, the postbounce phase, black hole formation, and the subsequent early hyperaccretion phase. We extract gravitational waves from the spacetime curvature and identify a unique gravitational wave signature associated with the early phase of collapsar formation.

Number fluctuations of sparse quasiparticles in a superconductor.

We have directly measured quasiparticle number fluctuations in a thin film superconducting Al resonator in thermal equilibrium. The spectrum of these fluctuations provides a measure of both the density and the lifetime of the quasiparticles. We observe that the quasiparticle density decreases exponentially with decreasing temperature, as theoretically predicted, but saturates below 160 mK to 25-55/µm(3). We show that this saturation is consistent with the measured saturation in the quasiparticle lifetime, which also explains similar observations in qubit decoherence times.

Prostate stem cell antigen is a promising candidate for immunotherapy of advanced prostate cancer.

Immunotherapy of prostate cancer (CaP) may be a promising novel treatment option for the management of advanced CaP. However, the lack of suitable tumor antigens remains a major obstacle for the rational design of vaccines. To characterize potential CaP antigens, we determined the mRNA expression of the prostate-specific genes C1, C2, C5, PAGE-1, and prostate stem cell antigen (PSCA) in hormone-refractory CaP, benign prostatic hyperplasia, CaP cell lines, and CaP specimens. Among these gene products, only expression of PSCA appears to be retained in the majority of advanced CaP samples, as shown by reverse transcription-PCR analyses. Peptide fragments of PSCA presented in the context of major histocompatibility molecules could serve as recognition targets for CD8 T cells, provided these lymphocytes were not clonally deleted or peripherally tolerized. Our goal was to determine whether the human T-cell repertoire could recognize PSCA-derived peptide epitopes in the context of a common class I allele, HLA-A0201. Of nine peptides that, according to HLA-A0201 binding motifs, were candidate ligands of A0201 class I molecules, three peptides were able to stabilize HLA-A0201 molecules on the cell surface. One of the latter peptides, encompassing amino acid residues 14-22, was capable of generating a PSCA-specific T-cell response in a human lymphocyte culture from a patient with metastatic CaP. PSCA-specific CTLs recognized peptide-pulsed targets as well as three prostate carcinoma lines in cytotoxicity assays, indicating that this peptide could be endogenously processed. In conclusion, our findings establish PSCA as a potential target for antigen-specific, T cell-based immunotherapy of prostate carcinoma.

The Buschke-Ollendorff syndrome: a case report of simultaneous osteo-cutaneous malformations in the hand.

BACKGROUND: We describe a male with functionally impairing radial deviation of the thumb who presented to us at 24 years of age. Two sclerotic skin lesions had been excised 7 years before because of consecutive skin contracture. Latest radiological examination showed a spotted pattern consistent with osteopoikilosis. CASE PRESENTATION: A corrective osteotomy of the thumb was carried out due to the patients discomfort. Facing the simultaneous osteo-cutaneous malformation we postulated a Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome is a rare autosomal-dominant hereditary disorder of connective tissue with typical osteo-cutaneous manifestations. To explore our hypothesis, biopsies were taken from the affected bone lesions and surrounding skin and soft tissue for histological investigation and genetic testing of the LEMD3 gene was performed on blood of the patient. The histology showed typical changes of the bone architecture and a fibrotic collagenous nodule of the skin. The genetic testing on DNA extracted from peripheral blood leucocytes confirmed a heterozygous loss of function mutation in the LEM domain-containing protein 3 (LEMD3) gene coding for the inner nuclear membrane protein MAN1, which causes osteopoikilosis by antagonizing transforming growth factor ß (TGF-ß) and bone morphogenetic protein (BMP) signalling. CONCLUSIONS: In atypical cases of simultaneous occurrence of fibrotic skin lesions and a spotted pattern in the X-ray we recommend the genetic screening of the LEMD3 gene. A correct diagnosis of Buschke-Ollendorff syndrome is necessary to spare patients from expensive investigations and to provide reassurance about the benign nature of the disease.

[Primary neuroendocrine tumor of the kidney. A rarity]. / Primärer neuroendokriner Tumor der Niere. Eine Rarität.

This article presents a rare case of a primary neuroendocrine tumor (NET) of the kidney. Abdominal magnetic resonance imaging (MRI) was performed in a 56-year-old man during the follow-up of an adrenal adenoma. Incidentally a renal tumor at the upper pole of the left kidney was diagnosed and was suspected of being a renal cell carcinoma. After partial nephrectomy a NET measuring 4.2 cm in diameter could be diagnosed histologically. An extrarenal primary tumor was ruled out by a postoperative gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) scan. A primary NET of the genitourinary tract is rare and less than 100 cases have been reported in the medical literature.

T cell immunity and interferon-gamma secretion during experimental allergic encephalomyelitis in Lewis rats.

An immunospot assay that detects single secretory cells was used to enumerate interferon-gamma secreting cells (IFN-gamma-sc) in mononuclear cell suspensions from the central nervous system (CNS) and peripheral lymphoid organs after actively induced experimental allergic encephalomyelitis (EAE) in Lewis rats. In the CNS compartment there was a significant increase in the number of IFN-gamma-sc preceding the onset of the clinical signs of EAE. Both in rats with EAE and rats immunized with Freund's complete adjuvant (FCA) the number of IFN-gamma-sc increased in peripheral lymphoid organs, as compared to non-immunized controls. In view of the potent immunoregulatory effects of IFN-gamma, its intra-CNS secretion may play a crucial role for clinicopathological events in EAE. To study the numbers of primed T cells that in response to myelin antigens produced IFN-gamma, mononuclear cell suspensions from peripheral lymphoid organs were precultured to allow for antigen uptake, presentation and T cell triggering, followed by enumeration of IFN-gamma-sc. T cells responding to a peptide of myelin basic protein (MBP) that previously have been shown encephalitogenic in Lewis rats, appeared initially and were quantitatively dominant over the course of EAE. Later, T cell reactivities to multiple regions of MBP appeared, showing that the concept of immunodominance in EAE is non-absolute and time dependent. Splenocyte cultures from EAE rats exposed to the different antigens showed a reduced number of IFN-gamma-sc compared to cultures not exposed to antigen, suggesting an antigen-induced suppression of T cell effector molecules.

Loss of heterozygosity on chromosome 16q, expression of her2/neu and p53 mutations in endometrial cancer.

We analyzed endometrial adenocarcinomas for mutations of the p53 anti-oncogene, expression of the HER2/neu oncogene and for loss of heterozygosity on chromosome 16q. p53 mutations were found in 3 of 25 tumors. Elevated expression of HER2/neu found in 7 of 24 tumors involves a mechanism other than gene amplification. LOH on chromosome 16q22-24 was observed in 4 of 13 informative tumors. Four of 25 endometrial tumors exhibited two or more alterations. Tumors with the highest HER2/neu protein level exhibited a negative progesterone receptor status. Accumulation of these changes may determine the biological behaviour of a subset of endometrial tumors.

Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus.

Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-gamma-like immunoreactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-gamma increased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-gamma producing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macrophage function during Wallerian degeneration in the distal stump.

Differentiation potential of ovarian dysgerminoma: an immunohistochemical study of 15 cases.

An immunohistochemical study of 15 ovarian formalin-fixed, paraffin-embedded dysgerminomas showed positive staining of tumor cells for vimentin in all cases. Ten dysgerminomas stained for cytokeratin 18. Desmin positivity of single tumor cells was detected in four dysgerminomas. Glial fibrillary acidic protein was present in two tumors. Prominent human beta chorionic gonadotropin staining was seen in one tumor. S-100 protein was found in two and carcinoembryonic antigen in one of the dysgerminomas. Placental alkaline phosphatase was present in 12 of the 15 tumors studied. The heterogeneity of the cytoskeletal profile and of other markers showed some similarities to our previously published results on testicular seminomas. Thus, in contrast to previous concepts, dysgerminoma, as is the case with its testicular counterpart the seminoma, appears to be capable of further differentiation, albeit at a primitive level. Our observations also may help to elucidate the relationship between dysgerminoma and other nondysgerminomatous ovarian germ cell tumors, and may be of help in the differential diagnosis with poorly differentiated carcinoma, ovarian lymphoma, or other germ cell tumors.

CDX-2 immunostaining in primary and secondary ovarian carcinomas.

AIMS: To assess the value of homeobox protein CDX-2 expression in the distinction between primary ovarian carcinomas and carcinomas metastatic to the ovary. METHODS: CDX-2 expression was assessed by immunohistochemistry in 120 serous, 68 endometrioid, 24 clear cell, and 16 mucinous carcinomas of the ovary. In addition, CDX-2 immunoreactivity was investigated in 20 metastases from adenocarcinomas to the ovary (15 of colorectal, two of gastric, one of appendiceal, one of pancreatic, and one of cervical origin) and their corresponding primary tumours. RESULTS: Almost all of the primary ovarian carcinomas lacked immunoreactivity for CDX-2. In contrast, 14 of the 16 metastases to the ovary from intestinal primaries showed CDX-2 immunoexpression. CONCLUSION: CDX-2 is a useful marker for differentiating primary ovarian carcinoma from carcinomas metastatic to the ovary.

Neurotrophic factors prevent the death of CNS neurons after spinal cord lesions in newborn rats.

The aim of this study was to determine if the exogenous administration of neurotrophic factors can rescue immature axotomized CNS neurons in vivo. After spinal cord hemisection in newborn rats, the exogenous administration of neurotrophic factors brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF), prevents the retrograde cell death of axotomized red nucleus neurons (and other brain stem spinal neurons) in vivo. Rescue of red nucleus neurons was maintained in the presence of BDNF, but only transiently maintained by NT-3 and NGF. Neurons within the nucleus dorsalis (Clarke's nucleus) of the spinal cord are also axotomized by this lesion. The application of exogenous NT-3, but not NGF or BDNF, rescued Clarke's nucleus neurons. These observations indicate that neurotrophic factors play a crucial role in the survival of CNS neurons in vivo during development and after injury. Furthermore, these results indicate that particular populations of neurons are dependent upon specific neurotrophic support after injury.

Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis.

Memantine, a clinically employed drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rat experimental autoimmune encephalomyelitis (EAE). Interestingly, this therapeutic effect was not due to dampened CNS inflammation, as assessed by immunohistochemical evaluation of spinal cord tissue. Furthermore, numbers of interferon gamma (IFN gamma) mRNA expressing cells were not decreased, as assessed by in situ hybridization. Systemic immunity in terms of numbers of IFN gamma secreting cells in response to immunodominant myelin basic protein (MBP) peptides ex vivo was not reduced, and non-toxic doses of memantine did not affect lymphocyte proliferation or IFN gamma secretion in vitro. Considering these findings, we hypothesize that effector mechanisms responsible for reversible neurological deficits in EAE may involve NMDA receptors, and this highlights neurons as targets during autoimmune neuroinflammation.

P53 mutations and loss of heterozygosity on chromosomes 8p, 16q, 17p, and 18q are confined to advanced prostate cancer.

We analysed 39 prostatic carcinomas for loss of heterozygosity on chromosomal arms 8p, 10q, 16q, 17p and 18q and for mutations in the p53 anti-oncogene. Loss of heterozygosity (LOH) on 8p was detected in one out of 5 informative tumors, LOH on 16q in 3 out of 21 tumors, LOH on 17p in 2 out of 18 tumors, and LOH on 18q in 2 out of 17 tumors. No deletions were observed on 10q in 14 informative tumors. p53 alterations occurred in 3 out of 38 examined tumors, comprising two point mutations and a small deletion. Chromosomal deletions and p53 mutations were confined to locally invasive prostatic carcinomas, suggesting that they are associated with the progression of some prostate cancers rather than with tumor initiation.

Intervention strategies to enhance anatomical plasticity and recovery of function after spinal cord injury.

Taken together, our studies indicate that (a) transplants mediate recovery of skilled forelimb movement as well as locomotor activity, (b) combinations of interventions may be required to restore reflex, sensory, and locomotor function to more normal levels after SCI, and (c) that remodeling of particular pathways may contribute to recovery of rather specific aspects of motor function. In conclusion, we suggest that it seems unlikely that any single intervention strategy will be sufficient to ensure regeneration of damaged pathways and recovery of function after SCI. Clearly, work from a number of laboratories indicates that the dogma that mature CNS neurons are inherently incapable of regeneration of axons after injury is no longer tenable. The issue, rather, is to identify and reverse the conditions that limit regeneration after SCI. After SCI, a hierarchy of "intervention-strategies" may be required to restore suprasegmental control leading to recovery of function. The hierarchy may be both temporal and absolute. For example, early interventions (such as the administration of methylprednisolone within hours of the injury) may be required to interrupt the secondary injury cascade and restrict the extent of damage after SCI. At the injury site itself, interventions to minimize the secondary injury effects may be followed by interventions to alter the environment at the site of injury to provide a terrain conducive to axonal elongation. For example, one might envision strategies to downregulate the expression of molecules that limit growth and upregulate the expression of those that support growth. Early after the injury, axotomized neurons may require neurotrophic support either for their survival or to initiate and maintain a cell body response supporting axonal elongation. There may be an absolute hierarchy as well. Particular populations of neurons may have very specific requirements for regenerative growth. For example, the conditions that enhance the regenerative growth of descending motor pathways may differ from those required by ascending sensory systems. One may also want to design strategies to restrict the plasticity of some pathways (e.g., nociceptive) and enhance the growth in other pathways. The demands on the CNS for anatomic reorganization after SCI may be far less formidable than one might at first imagine. If one assumes that recovery of function will require regenerative growth of large numbers of axons over long distances in a point-to-point topographically specific fashion, the idea of recovery of function becomes daunting. On the other hand, it has been shown in many studies and in many areas of the CNS that as little as 10% of a particular pathway can often subserve substantial function. Furthermore, regrowth over relatively short distances can have major functional consequences. For example, relatively modest changes in the level of SCI can have relatively profound effects on the functional consequences of injury. This is particularly true in cervical SCI: an individual with a C5/6 SCI is dramatically more impaired than one with C7/8 injury. One might envision relatively short distance growth across the injury site to re-establish suprasegmental control. Coupled with strategies to enhance the anatomic and functional reorganization of spinal cord circuitry caudal to the level of the injury, even modest long distance growth may have sufficient functional impact. One might imagine the ability to learn to "use" even modest quantities of novel inputs in functionally useful, appropriate ways.

[Adaptive immunotherapy of the advanced prostate cancer - cancer testis antigen (CTA) as possible target antigens]. / Adaptive Immuntherapie des fortgeschrittenen Prostatakarzinoms - Cancer Testis Antigene (CTA) als mögliche Zielantigene.

Prostate cancer (PCa) like other tumors expresses antigens that may serve as target for specific immunotherapy. Special antigen-presenting cells (e. g., dendritic cells) are capable of generating tumor-specific immunity. Cytotoxic T-cells (killer cells) are very effective against antigens and, consequently, against the respective tissue or tumor. Cancer testis antigens (CTA) are expressed in various human cancers but, aside from the testicles, not in normal tissue. Therefore, they are suitable for a specific tumor immunotherapy. We looked at different CTA (LAGE-1, PRAME, MAGE-C2, NY-ESO-1, SSX-2 and PAGE4) and their occurrence in prostatic cancer. Expression of CTA in various PCa cell lines and PCa material from patients was very heterogeneous. Only PAGE4 was expressed in primary PCa and in LnCaP cells as well as in hormone-dependent and hormone-refractory PCa probes. We conclude that PAGE4 should be further evaluated as a potential target for immunotherapy of PCa.

[Tuberculosis of the breast]. / Tuberkulose der Mamma.

The case of a 89-year-old women with mammary tuberculosis is reported. The diagnosis was based on histopathological and bacteriological examinations. Chest X-ray showed a lung-pleural tuberculosis, so we considered it a secondary organ manifestation.