Bone marrow failure by cytomegalovirus is associated with an in vivo deficiency in the expression of essential stromal hemopoietin genes

Bone marrow (BM) failure associated with cytomegalovirus (CMV) infection is a feared complication after clinical BM transplantation. Experiments in long-term BM cultures have indicated that BM stromal cells (BMSC) are targets of productive CMV infection, but an in situ infection of BM stroma remained to be documented, and the pathomechanism is open to question. Here we describe a murine in vivo model of lethal CMV aplastic anemia (CMV-AA). The reconstitution of hematopoietic progenitor cells expressing stem cell factor (SCF) receptor was found to be defective in CMV-AA. While murine CMV replication in permissive parenchymal tissues is cytolytic, the hematopoietic cord was found to be a site of very limited virus production with foci of reticular BMSC expressing the intranuclear viral IE1 protein, but with only a few BMSC positive for viral genome in the in situ hybridization. XX-XY BM chimeras were established in order to quantitate Y-chromosome-tagged BMSC by a PCR specific for the male-sex-determining gene Tdy. This approach revealed that murine CMV infection is not associated with a significant loss of BMSC. Despite the physical integrity of the stromal network, the functional integrity of the stroma was impaired. While housekeeping genes were expressed normally in BMSC of infected mice, the expression of genes encoding the essential hemopoietins SCF, granulocyte colony-stimulating factor, and interleukin-6 was markedly reduced. In conclusion, the mechanism of BM failure is not a stromal lesion but an insufficient stromal function. These findings explain CMV-AA as a manifestation of multiple hemopoietin deficiency.     

Eyeglass MEDRETE: practical considerations (a user''s guide)

Humans are exposed to a variety of potential developmental toxicants. This fact, combined with the knowledge that human development can be disrupted by "environmental" agents, has led to the development of methods designed to identify potential developmental toxicants. Currently, the principal method used to screen drugs and chemicals that are potential human developmental toxicants is the segment II study (i.e., a study in which prospective drugs and chemicals are tested in pregnant animals). Because of the cost and time involved in such studies and the pressure to reduce the number of animals used in such testing, alternative methods for developmental toxicity testing have been sought. This has resulted in a number of in vitro tests whose aim is to screen large numbers of agents quickly and inexpensively. Although numerous in vitro tests of developmental toxicity have been developed during the last 15 years, no one system or combination of tests have been validated for the purpose intended. Nonetheless, two systems--the limb bud/CNS micromass, and the chick embryo neural retina cell culture (CERC)--continue to be advanced as viable in vitro developmental toxicology tests. The purpose of this commentary is to evaluate the prospects for the development of an in vitro test system(s) that can screen the universe of drugs and chemicals and reliably identify those that require further study and those that do not. The conclusion of this investigator is that the prospects for validating such in vitro tests are not promising. This conclusion is based primarily on the lack of basic knowledge regarding the relevance of end points assayed in the micromass and CERC test systems to those end points known or thought to be critical for normal development.     

Lock-in detection for pulsed electrically detected magnetic resonance

We show that in pulsed electrically detected magnetic resonance (pEDMR) signal modulation in combination with a lock-in detection scheme can reduce the low-frequency noise level by one order of magnitude and in addition removes the microwave-induced non-resonant background. This is exemplarily demonstrated for spin-echo measurements in phosphorus-doped silicon. The modulation of the signal is achieved by cycling the phase of the projection pulse used in pEDMR for the readout of the spin state.     

Planning dysfunction in schizophrenia: impairment of potentials preceding fixed/free and single/sequence of self-initiated finger movements

To test the hypothesis of a planning dysfunction in schizophrenia using a precise temporal definition, the readiness potential (RP), a negative cortical wave preceding self-initiated movements and reflecting motor preparation processes, was studied in patients under stable medication and in controls. The supplementary motor area (SMA), known to be involved in the generation of the RP, has also been implicated in movement selection (fixed versus free) and complexity (single versus sequence). This is the first study using RP for the assessment of the influence of these factors on motor preparation in schizophrenics. Our results show that schizophrenics' RP amplitude is significantly lower than in controls at central and contralateral electrodes. However, RP amplitude increases with task difficulty in both groups, offering important new insight into classical SMA hypoactivation in schizophrenics performing motor tasks. Topographic analysis shows that RP amplitude is, for both groups, significantly higher in sequence than in single movements at fronto-central sites and higher for free than for fixed movements at centro-parietal sites. Finally, RP onset occurs significantly later in schizophrenics than in controls. These results support the view of a motor-preparation and decision-making dysfunction in schizophrenia. They are interpreted within the framework of a fronto-striatal disorder in this disease.     

Control of cytomegalovirus in bone marrow transplantation chimeras lacking the prevailing antigen-presenting molecule in recipient tissues rests primarily on recipient-derived CD8 T cells

Cytomegalovirus (CMV) infection during the transient immunodeficiency after bone marrow transplantation (BMT) develops into disease unless antiviral CD8 T cells are restored in due course. Histoincompatibility between donor and recipient is associated with increased risk. Complications may include a rejection response against the foreign major histocompatibility complex (MHC) antigens and a lack of antiviral control resulting from a misfit between donor-derived T cells and the antigenic viral peptides presented in recipient tissues. Here we have established a murine model of CMV disease after experimental BMT performed across a single MHC class I disparity. Specifically, BALB/c bone marrow cells expressing the prevailing antigen-presenting molecule Ld were transplanted into the Ld gene deletion mutant BALB/c-H-2(dm2), an experimental setting that entails a selective risk of host-versus-graft but not graft-versus-host response. The reconstituted T-cell population proved to be chimeric in that it consisted of Ld-positive donor-derived and Ld-negative recipient-derived cells. Pulmonary infiltrates did not include cytolytic T cells directed against Ld. This finding implies that the infection did not trigger a host-versus-graft response. Notably, upon adoptive transfer, donor-derived CD8 T cells preferentially protected tissues of donor genotype, whereas recipient-derived CD8 T cells protected tissues of either genotype. We infer from these data that the focus on immunodominant antigens presented by Ld within the donor cell population distracted the donor T cells from protecting recipient tissues and that protection in the chimeras was therefore primarily based on recipient T cells. As a consequence, T-cell chimerism after BMT should give a positive prognosis with respect to control of CMV.     

Full-wave analysis of radiating planar resonators with the methodof lines

The method of lines (MoL) is extended to analyze radiating planar resonators by the use of absorbing boundary conditions. For stratified layers, an equivalent network is derived to set up a system equation by simple multiplication of hybrid matrices. As an example, the complex resonant frequency of a microstrip patch is computed and compared to results achieved with the integral equation method in spectral domain. The radiation in the near-field region is depicted by a vector plot of the energy flow, given by the real part of the Poynting vector     

Dual polarized stacked SSFIP array antenna in C-band for beam-pointing

This paper presents the design and development of a wideband dual polarized planar array antenna of 4 × 6 elements in C-band with a centre frequency of 5.3?GHz. The radiating element is of stacked strip slot foam inverted patch (SSFIP) configuration. The complex excitation coefficients of the antenna have been chosen in order to achieve a fixed beam-pointing by 10° and side-lobe level better than ?15?dB. The array antenna offers a VSWR bandwidth of 20% for a VSWR ratio of 2:1. The simulated and measured antenna parameters are presented.     

沃尔夫绍夫绿色城市住宅 奥地利维亚纳

正近日,由GERNER GERNER PLUS设计的一座住宅楼在维也纳第十二区竣工,这座住宅楼是该事务所参加邀请赛作品之一,不仅为住户提供高质量生活空间,而且还附送一个宽敞的公共"小吃花园"。这是一座全新的充满工业风的LOFT公寓楼,四周建筑都大多经过改建,内含多个公寓,面积从45到77平方米不等,有出租屋、自有房也有养老福利房。现存建筑内部有部分在建造过程中毁坏,但房间高度仍然得以保留,这就给了房间LOFT公寓元素。所有房间都被设计成统一的立方体型,带有拱形天花板,也进一步增强了工业风感觉。整栋楼共有60间公寓房,一