Importance of localized skin infection in tick-borne encephalitis virus transmission

Arboviruses are transmitted to vertebrates by the "bite" of infected arthropods. Events at the site of virus deposition are largely unknown despite increasing evidence that blood-sucking arthropods immunomodulate their skin site of feeding. This question is particularly relevant for ixodid ticks that feed for several days. To examine events under conditions mimicking tick-borne encephalitis (TBE) virus transmission in nature (i.e., infected and uninfected Ixodes ricinus ticks feeding on the same animal), infected adult and uninfected nymphal ticks were placed in one retaining chamber (skin site A) and uninfected nymphs were placed within a second chamber posteriorly (skin site B) on two natural host species, yellow-necked field mice (Apodemus flavicollis) and bank voles (Clethrionomys glareolus). Virus transmission from infected to uninfected cofeeding ticks was correlated with infection in the skin site of tick feeding. Furthermore, virus was recruited preferentially to the site in which ticks were feeding compared with uninfested skin sites. Viremia did not correspond with a generalized infection of the skin; virus was not detected in an uninfested skin site (C) of 12/13 natural hosts that had viremia levels > or = 2.0 log10 ic mouse LD50/0.02 ml blood. To characterize infected cells, laboratory mouse strains were infested with infected ticks and then explants were removed from selected skin sites and floated on culture medium. Numerous leukocytes were found to migrate from the skin explants of tick feeding sites. Two-color immunocytochemistry revealed viral antigen in both migratory Langerhans cells and neutrophils; in addition, the migratory monocyte/macrophages were shown to produce infectious virus. The results indicate that the local skin site of tick feeding is an important focus of viral replication early after TBE virus transmission by ticks. Cellular infiltration of tick feeding sites, and the migration of cells from such sites, may provide a vehicle for transmission between infected and uninfected cofeeding ticks that is independent of a patent viremia. The data support the hypothesis that viremia is a product, rather than a prerequisite, of tick-borne virus transmission.     

Encephalopathy during oral treatment with bismuth salts

Side effects of orally administered bismuthic salts have been known for many years. Many systems are involved, including the digestive and urinary. The authors discuss a recently discovered effect on the central nervous system, termed "bismuth encephalopathy". In the light of the medical literature reviewed, two original aspects are stressed: the clinical symptoms are stereotyped and completely reversible, and the distribution of the disease is almost epidemic, being limited in time and space. The prodromes include confusion, asthenia, slowing of mental functions and disturbance of gait. The clinical picture is dominated by four major symptoms: confusion (again), ataxia, dysarthria and, above all, myoclonic jerks. In conclusion, various pathogenetic hypotheses are considered. The purpose of this study is to enable the general practitioner to detect the development of this condition early in treatment with oral bismuthic salts. Withdrawal of the medication always results in normalization of the patient's condition.     

Recognition of depressed affect in hospitalized psychiatric patients: staff and patient perceptions

A comparison of self-report vs. observer rating of depressed mood in a heterogenous inpatient population revealed wide variations in concordance among diagnostic groups. Patients diagnosed as having Affective Psychosis and "Other' illnesses showed the highest correlation between four self-report scales and an observer rating scale. Patients with a diagnosis of depressive Neurosis showed only modest correlation, while Schizophrenics revealed no significant correlation, on these instruments, suggesting inconsistent communication of affect from Schizophrenic patients to observers. In contrast, when self-report scales were intercorrelated, patients in all four diagnostic categories showed highly significant correlations, indicating that they were consistently reporting their affective state on these instruments. The implications of these findings for future research as well as for practical clinical management are discussed.     

Organic Thin‐Film Photovoltaic Cells Based on Oligothiophenes with Reduced Bandgap

The best polymeric solar cells reported so far are based on a so‐called bulk heterojunction of a polythiophene as donor and a soluble fullerene derivative as acceptor. However, these cells still suffer from an unsatisfying photovoltage, typically below 0.7 V. Here, we show that we can achieve higher photovoltages using a new terthiophene end‐capped with electron withdrawing dicyanovinyl groups (DCV3T) that increase both the ionization energy and even more strongly the electron affinity of the compound. The new material is tested in cells using a photoactive heterojunction to separate the excitons generated in the oligomer and a p‐doped wide‐gap transport layer. The solar cells show an open circuit voltage of up to 1.04 V and a broad spectral sensitivity band ranging from 420 nm to 650 nm. Solar cells based on such oligothiophenes are promising candidates for stacked organic solar cells tailored to the sun‐spectrum. Moreover, we present first examples of a new concept for organic solar cells: By blending DCV3T with fullerene C₆₀, an enhanced generation of triplet excitons on the oligomer can be achieved via a back and forth transfer of excitons (ping‐pong‐effect).     

Growth and dielectric properties of Ta_2O_5 single crystals grown by laser heated pedestal growth technique

Ta2O5 single crystals have been grown by the laser heated pedestal growth (LHPG) technique up to several centimeters length with diameter of 1.1 mm. The crystal, characterized by X-ray diffraction, dielectric measurement, and thermal expansion analysis, has Htri-Ta2O5 symmetry. Dielectric permittivity, loss tangent along [001] and [110] direction were investigated over the temperature range from -80 ℃ to 100 ℃. Large dielectric anisotropy in Ta2O5 single crystal was observed. At room temperature, the dielectric permittivities (1 MHz) along [001] and [110] are 33.2 and 231.9, respectively. The reason of dielectric enhancement in Ta2O5 crystal grown by LHPG was also discussed.     

基于流形正则化非负矩阵分解的高光谱数据降维

采用基于流形正则化非负矩阵分解(MR-NMF)的高 光谱数据降维方法。新方 法通过构建样本的近邻图描述数据几何结构,然后将其作为正则项加入NMF的目标函 数中进行组合优化。在真实的高光谱数据集HYDICE上进行的实验结果表明,新方法能 够提高高光谱图像分类的精度。     

Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images

Volumetric magnetic resonance image (MRI)-based morphometry was performed on the brains of 30 normal children (15 males and 15 males) with a mean age of 9 years (range 7-11 years). This age range lies in a late but critical phase of brain growth where not volumetric increment will be small but when the details of brain circuity are being fine-tuned to support the operations of the adult brain. The brain at this age is 95% the volume of the adult brain. The brain of the female child is 93% the volume of the male child. For more than 95% of brain structures, the volumetric differences in male and female child brain are uniformly scaled to the volume difference of the total brain in the two sexes. Exceptions to this pattern of uniform scaling are the caudate, hippocampus and pallidum, which are disproportionately larger in female than male child brain, and the amygdala, which is disproportionately smaller in the female child brain. The patterns of uniform scaling are generally sustained during the final volumetric increment in overall brain size between age 7-11 and adulthood. There are exceptions to this uniform scaling of child to adult brain, and certain of these exceptions are sexually dimorphic. Thus, with respect to major brain regions, the cerebellum in the female but not the male child is already at adult volume while the brainstem in both sexes must enlarge more than the brain as a whole. The collective subcortical gray matter structures of the forebrain of the female child are already at their adult volumes. The volumes of these same structures in the male child, by contrast, are greater than their adult volumes and, by implication, must regress in volume before adulthood. The volume of the central white matter, on the other hand, is disproportionately smaller in female than male child brain with respect to the adult volumes of cerebral central white matter. By implication, relative volumetric increase of cerebral central white matter by adulthood must be greater in the female than male brain. The juxtaposed progressive and regressive patterns of growth of brain structures implied by these observations in the human brain have a soundly established precedent in the developing rhesus brain. There is emerging evidence that sexually dimorphic abnormal regulation of these terminal patterns of brain development are associated with gravely disabling human disorders of obscure etiology.