X-ray quasi-periodic eruptions from two previously quiescent galaxies.

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data1,2, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole3,4. Here we report observations of QPEs in two further galaxies, obtained with a blind and systematic search of half of the X-ray sky. The optical spectra of these galaxies show no signature of black hole activity, indicating that a pre-existing accretion flow that is typical of active galactic nuclei is not required to trigger these events. Indeed, the periods, amplitudes and profiles of the QPEs reported here are inconsistent with current models that invoke radiation-pressure-driven instabilities in the accretion disk5-9. Instead, QPEs might be driven by an orbiting compact object. Furthermore, their observed properties require the mass of the secondary object to be much smaller than that of the main body10, and future X-ray observations may constrain possible changes in their period owing to orbital evolution. This model could make QPEs a viable candidate for the electromagnetic counterparts of so-called extreme-mass-ratio inspirals11-13, with considerable implications for multi-messenger astrophysics and cosmology14,15.

Single walled carbon nanotube/Si heterojunctions for high responsivity photodetectors.

Single walled carbon nanotube/n-Si (SWCNT/n-Si) hetero-junctions have been obtained by depositing SWCNT ultra-thin films on the surface of an n-Si substrate by dry transfer method. The as obtained junctions are photo sensitive in the measured wavelength range (300-1000 nm) and show zero bias responsivity and detectivity values of the order of 1 A W-1 and 1014 Jones respectively, which are higher than those previously observed in carbon based devices. Moreover, under on-off light excitation, the junctions show response speed as fast as 1 µs or better and noise equivalent powers comparable to commercial Si photomultipliers. Current-voltage measurements in dark and under illumination suggest that the devices consist of Schottky and semiconductor/semiconductor junctions both contributing to the fast and high responses observed.

NbN superconducting nanonetwork fabricated using porous silicon templates and high-resolution electron beam lithography.

Superconducting NbN nanonetworks with a very small number of interconnected nanowires, with diameter of the order of 4 nm, are fabricated combining a bottom-up (use of porous silicon nanotemplates) with a top-down technique (high-resolution electron beam lithography). The method is easy to control and allows the fabrication of devices, on a robust support, with electrical properties close to a one-dimensional superconductor that can be used fruitfully for novel applications.

Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus.

Nonobese diabetic (NOD) mice are the experimental prototype of type 1 insulin-dependent diabetes mellitus (IDDM). These mice develop a characteristic autoimmune lesion in the pancreatic islets of Langerhans, where infiltrating lymphocytes destroy beta cells, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. This IDDM, which closely resembles that in humans, is prevented by infecting NOD mice with particular strains of lymphocytic choriomeningitis virus (LCMV), including Armstrong 53b, Traub, WE, and Pasteur. In contrast, the LCMV Armstrong 53b variant, Clone 13, fails to abort IDDM. Hence, although Clone 13 establishes a persistent infection that endures throughout the life spans of NOD mice, their hyperglycemia, hypoinsulinemia, and lymphocytic infiltration into the islets of Langerhans still occur. Genetic reassortant viruses generated between the IDDM therapeutic strain of LCMV Pasteur and the nontherapeutic variant, LCMV Clone 13, were used to treat NOD mice. By using such reassortants and both parental strains of virus to infect NOD mice, the prevention of IDDM was mapped to the S RNA segment of LCMV Pasteur.

An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein.

The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

Scanning tunneling microscopy and Raman evidence of silicene nanosheets intercalated into graphite surfaces at room temperature.

Highly oriented pyrolytic graphite (HOPG) is an inert substrate with a structural honeycomb lattice, well suited for the growth of a two-dimensional (2D) silicene layer. It was reported that when Si atoms are deposited on the HOPG surface at room temperature, they arrange into two configurations: silicene nanosheets and three-dimensional clusters. In this work we demonstrate, by using scanning tunneling microscopy (STM) and Raman spectroscopy, that a third configuration stabilizes in the form of Si 2D nanosheets intercalated below the first top layer of carbon atoms. The Raman spectra reveal a structure located at 538 cm-1 which we ascribe to the presence of sp2 Si hybridization. Moreover, the silicon deposition induces several modifications in the graphite D and G Raman modes, which we interpret as experimental evidence of the intercalation of the silicene nanosheets. The Si atom intercalation at room temperature takes place at the HOPG step edges and it detaches only the outermost graphite layer inducing a strong tensile strain mainly concentrated on the edges of the silicene nanosheets. Theoretical calculations of the structure and energetic viability of the silicene nanosheets and of the strain distribution on the outermost graphite layer and its influence on the Raman resonances support the STM and Raman observations.

Measurement of 14MeV neutron-induced prompt gamma-ray spectra from 15 elements found in cargo containers.

Within the EURopean Illicit TRAfficking Countermeasures Kit (EURITRACK) project, the gamma-ray spectra produced in a series of materials by 14-MeV tagged-neutron beams have been collected in the inspection portal equipped with large volume NaI(Tl) detectors, in order to build a database of signatures for various elements: C, N, O, Na, Al, Si, Cl, K, Ca, Cr, Fe, Ni, Cu, Zn, Pb. The measured spectra have been compared with prediction from Monte Carlo simulations to verify the consistency of the relevant nuclear data inputs. This library of measured 14-MeV neutron-induced gamma-ray spectra is currently used in a data processing algorithm to unfold the energy spectra of the transported goods into elementary contributions, thus allowing material identification.

Prognostic significance of cell kinetics in laryngeal squamous cell carcinoma: clinicopathological associations.

A consecutive series of 99 untreated patients undergoing radical surgical resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our purpose was to analyze the predictive relevance of proliferative variables studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected mitotic (M/V) index, and S-phase fraction (SPF)] on clinical outcome in relation to DNA ploidy and clinicopathological features. All of the patients were followed up for a median of 32 months (range, 5-58 months). A weak, but significant, positive correlation was found between M/V and PCNA indices (except the PCNA weighted mean index:labeling index ratio) or these indices and SPF. At univariate analysis, node positivity (P < 0.05), poor histological grade (P < 0.01), DNA aneuploidy (P < 0.01), a high SPF (P < 0.01), and a high M/V index (P < 0.05) proved to be related significantly to quicker relapse, whereas T4 (P < 0.05), subglottic site (P < 0.05), DNA aneuploidy (P < 0.01) and a high SPF (P < 0.01) were related significantly to shorter overall survival. With multivariate analysis, a high SPF (> 12.1%) and histological grade (G3) were related to the risk of relapse (relative risk, 8.65 and 5.45, respectively), whereas only a high SPF was related independently to the risk of death (relative risk, 7.30). Our study has identified SPF, in addition to histological grade, as an important biological indicator in laryngeal carcinomas.

A novel calmodulin-like gene from the nematode Caenorhabditis elegans.

A novel gene from the nematode Caenorhabditis elegans was isolated by hybridization with a human calmodulin complementary DNA probe. This gene, cal-1, is present at one copy per haploid genome. In-situ hybridization of the cloned gene to metaphase chromosomes allowed us to assign it to the nematode linkage group IV. The polypeptide predicted from the sequence of this gene displays structural features of both calmodulin and troponin C.

The promyelocytic leukemia protein PML has a pro-apoptotic activity mediated through its RING domain.

The promyelocytic leukemia protein PML is known to form nuclear multiprotein complexes which are compromised in several pathogenic conditions including acute promyelocytic leukemia. We show that in cells infected with a single stranded RNA virus, which relocates PML bodies to the cytoplasm, the infected cells are more resistant to serum starvation induced apoptosis than their uninfected counterparts. Antisense PML oligonucleotides increase cell survival under serum deprivation conditions indicating that PML is directly involved in the apoptotic activity. Transient transfection studies have indicated that this pro-apoptotic activity of PML is mediated through the zinc binding region known as the RING finger. Viral attack of PML nuclear bodies appears to allow the virus to deregulate host cell apoptotic machinery in order to establish chronic infection.

Novel LCMV-specific H-2k restricted CTL clones recognize internal viral gene products and cause CNS disease.

H-2k (C3H/Hej) cytotoxic T lymphocytes (CTL) specific for lymphocytic choriomeningitis virus (LCMV) were cloned. Three clones recognizing internal viral antigens were studied. One such CTL clone recognized neither the glycoprotein nor nucleoprotein encoded by the viral short RNA segment, but reacted with a protein encoded by the long RNA segment, either the viral polymerase, or the Z protein. This one clone, in addition to primary CTL harvested from immunized C3H mice, failed to lyse target cells expressing the Z protein, suggesting recognition was to the viral polymerase. Two other clones recognized the viral nucleoprotein, amino acids 93-100, as determined by protein deletion and peptide mapping studies. When introduced directly into the central nervous systems of LCMV-infected histocompatible mice, all clones were active in vivo and capable of causing immunopathologically mediated death.

Biochemical and immunological evidence that the 11 kDa zinc-binding protein of lymphocytic choriomeningitis virus is a structural component of the virus.

The completed sequence of the arenavirus, lymphocytic choriomeningitis virus, revealed a new gene encoding a small protein with a single zinc-binding domain. The cDNA for this gene has been expressed in E. coli to produce fusion protein that has been used to raise antisera. The antisera facilitated the positive identification of the p11 'Z' gene product as a structural component of the virion. A related arenavirus, Tacaribe, has a comparable p11 gene product. The abundance of the p11 Z protein relative to other virion components has been determined by metabolic labeling. Triton X-114 extraction and dimethyl suberimidate-HCl crosslinking indicate that the p11 Z protein is a hydrophobic protein associated with the nucleocapsid of the virion core.

The lymphocytosis-promoting agent pertussis toxin affects virus burden and lymphocyte distribution in the SIV-infected rhesus macaque.

Pertussis toxin from the gram-negative bacterium Bordetella pertussis is an ADP-ribosylase that modifies Gi proteins in mammalian lymphocytes and inhibits their capacity to traffic from blood into lymphoid tissues. We used this compound to induce lymphocytosis in rhesus macaques and to study its effects on SIV infection. Pertussis toxin injected at 25 micrograms/kg induced a transient lymphocytosis that peaked 3-8 days after administration and caused a rapid, transient decrease in the frequency of infectious cells in blood as judged by in vitro virus isolation assays. Lymphocyte subsets were altered during the lymphocytosis interval and sustained changes in CD8+ T cell levels were noted as long as 53 days after pertussis toxin injection. In situ hybridization studies showed that pertussis toxin altered the distribution of viral RNA in lymph nodes during the interval of lymphocytosis, and caused long-term changes with decreased virus replication in some tissue specimens.

Malignant myoepithelioma of the breast - a case-history and review of literature.

A malignant myoepithelioma, mainly intraductally growing, of the breast was studied, emphasizing the immunohistological features of such tumors, in comparison with the more common, architecturally similar, infiltrating ductal carcinoma with intraductal component. Immunohistochemically, cell population of the tumor studied expressed intense reaction to alpha-SM-actin, cytokeratin 14, vimentin, S-100 protein and collagen IV antibodies, confirming myoepithelial differentiation. Since myoepitheliomas of the breast are very rare, complete knowledge of these neoplasms has not been attained. Nevertheless, histogenetic investigations may be useful in differentiating this type of tumor, from the above one, which is known to be characterized by severe clinical and prognostic implications.

Epithelial-myoepithelial carcinoma of the salivary glands: a clinico-pathologic, immunohistochemical and DNA flow cytometric study of three cases.

Epithelial-myoepithelial carcinoma is a rare neoplasia of the salivary glands. Histologic, immunohistochemical and flow cytometry analysis were used to study three new cases involving the major salivary glands of two women and one man. The mean age was 66.7 years. Immunohistochemistry confirmed the epithelial-myoepithelial dualism of the tumors: the predominant growth pattern showed ducts made up of an external myoepithelial layer and an internal epithelial layer. Proliferative activity, assessed by means of the PCNA and Ki-67 immunostaining and the study of the S-phase with flow cytometric analysis, proved to be higher in a recurrent case. All three cases were diploid. The use of immunohistochemical and flow cytometric techniques for the assessment of proliferative activity would seem to be an efficient method for the selection of a subgroup of epithelial-myoepithelial carcinomas with unfavorable prognosis.

Correlation of an estrogen receptor-related phosphoprotein with histopathological features in breast cancer.

A series of 65 cases of different histological types of breast carcinoma was investigated for the immunohistochemical location of the estrogen receptor-related, 29 kD phosphoprotein using the ER-D5 monoclonal antibody. The ER-D5 response is heterogeneous in relation to some therapeutic limitations and is correlated with histopathological features of the tumors and survival. The main parameters for evaluation of breast cancers are reviewed, both those that are statistically correlated and those that are not apparently always correlated but are known to have considerable biological meaning, such as the ER-status of tumors.

Macaque models for early immunosuppression and T cell loss during acute immunodeficiency virus infections.

The interval of acute infection with immunodeficiency viruses is critically important for determining the long-term rate of disease progression. The steps of initial infection, systemic dissemination, and explosive replication of pathogenic SIV or SHIV in macaques are being mapped to show the mechanisms responsible for remodeling host immunity, for establishing the persistent infection, and for promoting disease progression. Here, we describe recent studies on two ways in which CD4+ T cell populations are depleted during acute infection. Initially, we discuss recent work on the mechanisms for CD4+ T cell-mediated, MHC-unrestricted cytolysis. This mechanism shows how even soluble viral antigens such as the envelope glycoprotein, can prime CD4+ lymphocytes to be both effector and target cells in an unrestricted cytolysis mechanism. The consequence of unrestricted cytolysis is a more rapid destruction of the CD4+ T cell population. Secondly, we discuss the broader issue of T cell hyperactivation during acute infection. Inappropriate activation of this lymphocyte population renders cells susceptible to activation induced cell death and also increases the rate of virus replication. Macaque immunization studies have shown a clear role for extracellular Tat in hyperactivation. These two mechanisms, unrestricted cytolysis and T cell hyperactivation, are components of the acute infection that remodel host immunity and dictate the rate of progression to AIDS.

Evaluation of integrated morpho-biological indicators in breast cancer.

A series of 71 patients undergoing surgery for primary breast carcinoma was prospectively studied in order to verify the relationships between clinical and pathological variables, proliferative indexes and DNA-ploidy. Significant correlations between proliferative indexes were found; conversely, DNA-ploidy showed no correlation with either PCNA/cyclin or AgNORs, but only with flow cytometry S-phase fraction (FCM-S) and IF-vimentin. In the 42 patients with a mean follow-up of 42 months, disease-free rate was best predicted by nuclear grade (p < 0.001), histological grade (p < 0.001), mitoses (p 0.001), IF-vimentin (p 0.002), FCM-S (p 0.002), PCNA (p 0.005) and Ag-NORs (p 0.007).

Characterization of anomalous pair currents in Josephson junction networks.

Measurements performed on superconductive networks shaped in the form of planar graphs display anomalously large currents when specific branches are biased. The temperature dependences of these currents evidence that their origin is due to Cooper pair hopping through the Josephson junctions connecting the superconductive islands of the array. The experimental data are discussed in terms of theoretical models which predict, for the system under consideration, an inhomogeneous Cooper pair distribution on the superconductive islands of the network as a consequence of a Bose-Einstein condensation phenomenon.

Superconducting anisotropy in (CaCuO2)n/(SrTiO3)m superlattices.

The superconducting properties of (CaCuO2)n/(SrTiO3)m artificial superlattices have been investigated via transport measurements under the application of external magnetic fields. The coherence lengths in the plane of the substrate and in the direction perpendicular to it (ξab and ξc, respectively) have been measured while varying m, the thickness of the SrTiO3 block. The results show that with increasing m, i.e. with increasing structural anisotropy, the superconducting anisotropy γ = ξab/ξc decreases. This apparent anomalous relation between the structural and the superconducting anisotropies suggests that γ is more affected by local doping at the interface rather than by the separation between the superconducting blocks. This interpretation of the experimental results has been confirmed by both the irreversibility lines and the magnetic field dependence of the activation energy for fluxon motion.