The following essay discusses Herman Melville’s “I and My Chimney” (1856) as a text that engages architecture and writing as interrelated systems of signification. Fueled by a variety of historical developments, domestic architecture emerges as a powerful purveyor of meaning in the antebellum decades. Architecture, in this cultural context, is construed in analogy to writing (and, to some extent, vice versa), as creating houses-as-texts that tell stories about their inhabitants in terms of their individual, familial, and national identities. Thus conceived, domestic architecture is characteristically enlisted in the articulation and stabilization of hegemonic narratives of, e. g., gender and nationhood. Melville’s text invokes this cultural convention to cast the signifying function that architecture and writing perform as being vulnerable and in crisis. This crisis is narrated by an idiosyncratic narrator for whom the semiotic instability documented by his narrative resonates with the social and cultural vulnerability that he experiences—his authority as master of his house and family is challenged in the course of the tale, along with the structural integrity of his chimney with which he wants to symbolically reinforce his authority. I argue that this crisis of signification performs double work in the text. On the one hand, it serves to articulate the anxiety of mid-nineteenth-century cultural elites about what they perceive as a cultural decline. On the other hand, allegedly dysfunctional signification unfolds a critical potential, bringing to light things which ‘functional’ signification had worked to conceal and thereby unlocking hermetic narratives of self, family, and nation.

Background: Behavioral disturbances following chemotherapy with cisplatin are rare. Here, we report a patient with temporary loss of moral behavior in the setting of cisplatin-based chemotherapy for treatment of tonsillar cancer. Case presentation: A 66-year-old Caucasian male with no psychiatric or violent history was started on chemotherapy with cisplatin for treatment of tonsillar cancer. During the following weeks, the patient developed profound personality changes involving volatile emotions and impulsive aggression with verbal and physical assaults on others. Admitted to the hospital, the patient lacked any awareness that his behavior was wrong. Chemotherapy was discontinued and the patient was prescribed risperidone. Aside from mild cognitive impairment, comprehensive neuropsychological, neuroradiological and lab testing were unremarkable. Three weeks following cessation of chemotherapy, the patient had recovered to his original mental state and he was completely aware of his wrongdoing and social misconduct. Conclusion: Since neurotoxic effects of chemotherapeutics on the brain are not yet sufficiently elucidated, our case emphasizes that early signs of behavioral abnormalities in patients receiving chemotherapy should trigger comprehensive psychiatric evaluation and ongoing monitoring of the patients’ mental state.

Background: The clinical outcome of hip resurfacing (HR) as a demanding surgical technique associated with a substantial learning curve depends on the position of the femoral component. The aim of the study was to investigate the effects of the level of surgical experience on computer-assisted imageless navigation concerning precision of femoral component positioning, notching, and oversizing rate, as well as operative time. Methods: Three surgeons with different levels of experience in both HR and computer-assisted surgery (CAS) prepared the femoral heads of 54 synthetic femurs using the Durom TM Hip Resurfacing (Zimmer, Warsaw, IN, USA) system. Each surgeon prepared a total of 18 proximal femurs using the Navitrack® system (ORTHOsoft Inc., Montreal, Canada) or the conventional free-hand Durom TM K-wire positioning jig. The differences between planned and postoperative stem shaft angle (SSA) and anteversion angle in standardized x-rays were measured and the operative time, not including the time for calibrating the CAS-system, was documented. Notching was evaluated by the three surgeons in a randomized manner. Oversizing was determined by the difference of the preoperative determined cap and the cap size advised by the CAS-system. Results: CAS significantly reduced the overall mean deviation between planned and postoperative SSA in comparison with the conventional procedure (mean ± SD, 1 ± 1.7° vs. 7.4 ± 4.4°, P <0.01) regardless of the surgeon’s level of experience. The incidence of either varus or valgus SSA deviations exceeding 5° were 1/27 for CAS and 15/27 for the conventional method, respectively (P<0.001), corresponding to a reduction by 97%. Using CAS, the rate of notching was reduced by 100%. Conclusions: The accuracy of femoral HR component orientation is significantly increased by use of CAS regardless of the surgeon’s level of experience in our preclinical study. Thus, imageless computer-assisted navigation can be a valuable tool to improve implant positioning in HR for surgeons at any stage of their learning curve.

The role of competition in tree communities is increasingly well understood, while little is known about the patterns and mechanisms of the interplay between above- and belowground competition in tree communities. This knowledge, however, is crucial for a better understanding of community dynamics and developing adaptive near-natural management strategies. We assessed neighbourhood interactions in an unmanaged old-growth European beech (Fagus sylvatica) forest by quantifying variation in the intensity of above- (shading) and belowground competition (crowding) among dominant and co-dominant canopy beech trees during tree maturation. Shading had on average a much larger impact on radial growth than crowding and the sensitivity to changes in competitive conditions was lowest for crowding effects. We found that each mode of competition reduced the effect of the other. Increasing crowding reduced the negative effect of shading, and at high levels of shading, crowding actually had a facilitative effect and increased growth. Our study demonstrates that complementarity in above- and belowground processes enable F. sylvatica to alter resource acquisition strategies, thus optimising tree radial growth. As a result, competition seemed to become less important in stands with a high growing stock and tree communities with a long continuity of anthropogenic undisturbed population dynamics. We suggest that growth rates do not exclusively depend on the density of potential competitors at the intraspecific level, but on the conspecific aggregation of large-diameter trees and their functional role for regulating biotic filtering processes. This finding highlights the potential importance of the rarely examined relationship between the spatial aggregation pattern of large-diameter trees and the outcome of neighbourhood interactions, which may be central to community dynamics and the related forest ecosystem services.

Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. We investigated the role of ALADIN in the human adrenocortical cell line NCI-H295R1 by either over-expression or down-regulation of ALADIN. Our findings indicate that AAAS knock-down induces a down-regulation of genes coding for type II microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of precursor metabolites required for glucocorticoid and androgen production. Furthermore we demonstrate that ALADIN deficiency leads to increased susceptibility to oxidative stress and alteration in redox homeostasis after paraquat treatment. Finally, we show significantly impaired nuclear import of DNA ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. We conclude that down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting our knock-down cell model as an important in-vitro tool for studying the adrenal phenotype in triple A syndrome.

Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication.

Karst aquifers are characterized by highly conductive conduit flow paths embedded in a less conductive fissured and fractured matrix resulting in strong permeability contrasts with structured heterogeneity and anisotropy. Groundwater storage occurs predominantly in the fissured matrix. Hence, most karst models assume quasi steady-state flow in conduits neglecting conduit associated drainable storage (CADS). The concept of CADS considers storage volumes, where karst water is not part of the active flow system but rather hydraulically connected to conduits (for example karstic voids and large fractures). The disregard of conduit storage can be inappropriate when direct water abstraction from karst conduits occurs, e.g. large scale pumping. In such cases, CADS may be relevant. Furthermore, the typical fixed head boundary condition at the karst outlet can be inadequate for water abstraction scenarios because unhampered water inflow is possible. The objective of this paper is to analyze the significance of CADS and flow-limited boundary conditions on the hydraulic behavior of karst aquifers in water abstraction scenarios. To this end, the numerical hybrid model MODFLOW-2005 Conduit Flow Process Mode 1 (CFPM1) is enhanced to account for CADS. Additionally, a fixed-head limited-flow (FHLQ) boundary condition is added that limits inflow from constant head boundaries to a user-defined threshold. The affect and proper functioning of these modifications is demonstrated by simplified model studies. Both enhancements, CAD storage and the FHLQ boundary, are shown to be useful for water abstraction scenarios within karst aquifers. An idealized representation of a large-scale pumping test in a karst conduit is used to demonstrate that the enhanced CFPM1 is potentially able to adequately represent water abstraction processes in both the conduits and the matrix of real karst systems.

We present an unusual case of a late recurrent central neurocytoma that was rediagnosed as an ependymoma and neurocytoma in accordance with changes in histological classifications. Case Description. A 56-year-old male teacher presented with incomplete transverse syndrome due to several intradural extramedullary tumors at the level of lumbar vertebrae 1–3. The histological diagnosis at the time was atypical ependymoma. One year later, two additional tumors were removed at the L5-S1 vertebral level. For 12 years, the patient remained tumor free on followup. Fourteen years after the initial diagnosis, the patient presented with thoracic paresthesias due to two new extramedullary tumors in the C7-T1 and the T8-T9 vertebral levels. After complete removal of the tumors, a radiological survey revealed an intracranial lesion in the third ventricle. Five months later, an additional lesion recurrence was removed surgically. The most recent histological diagnosis revealed an atypical central neurocytoma. In retrospect, the previous tumors were reclassified as neurocytoma according to the additional immunohistochemistry evidence. Discussion. There is no standard adjuvant treatment regimen for atypical neurocytoma; therefore, the patient is currently under close followup. Modern histopathological diagnosis is essential in these cases. Potential routes for dissemination of the tumor should be considered upon first recurrence.

The use of reporter gene fusions to assess cellular processes such as protein targeting and regulation of transcription or translation is established technology in archaeal, bacterial, and eukaryal genetics. Fluorescent proteins or enzymes resulting in chromogenic substrate turnover, like β-galactosidase, have been particularly useful for microscopic and screening purposes. However, application of such methodology is of limited use for strictly anaerobic organisms due to the requirement of molecular oxygen for chromophore formation or color development. We have developed β-lactamase from Escherichia coli (encoded by bla) in conjunction with the chromogenic substrate nitrocefin into a reporter system usable under anaerobic conditions for the methanogenic archaeon Methanosarcina acetivorans. By using a signal peptide of a putative flagellin from M. acetivorans and different catabolic promoters, we could demonstrate growth substrate-dependent secretion of β-lactamase, facilitating its use in colony screening on agar plates. Furthermore, a series of fusions comprised of a constitutive promoter and sequences encoding variants of the synthetic tetracycline-responsive riboswitch (tc-RS) was created to characterize its influence on translation initiation in M. acetivorans. One tc-RS variant resulted in more than 11-fold tetracycline-dependent regulation of bla expression, which is in the range of regulation by naturally occurring riboswitches. Thus, tc-RS fusions represent the first solely cis-active, that is, factor-independent system for controlled gene expression in Archaea.

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