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Chronic kidney disease (CKD) is a complex disease affecting >10% of the global population, with large between- and within-continent variability reflecting major environmental effects. To identify molecular targets for treatment, genome-wide association study meta-analyses (GWAMAs) of CKD-defining traits have identified hundreds of genetic loci in aggregated populations. However, while GWAMAs estimate the average allelic effect across studies, single population studies may be relevant to unravel specific mechanisms. To assess whether an individual study from a specific population could extend existing knowledge on kidney function genetics, we selected 147 kidney function relevant loci identified by a large European ancestry GWAMA, assessing their association with the glomerular filtration rate estimated from serum creatinine (eGFRcrea) in the Cooperative Health Research In South Tyrol (CHRIS) study (n=10,146), conducted in an Alpine region where thyroid dysfunction is common. We replicated associations with single nucleotide polymorphisms (SNPs) at 11 loci, showing up-to-5.4 times larger effect sizes than in the corresponding GWAMA, not explainable by minor allele frequency differences. Systematic mediation analysis across 70 quantitative traits identified serum magnesium, the activated partial thromboplastin time, and serum urate as partial mediators of the eGFRcrea associations atSHROOM3,SLC34A1, andIGF1R, respectively. Given that free triiodothyronine and thyroxine were effect modifiers across all loci, we conducted SNP-by-thyroid stimulating hormone (TSH) interaction analyses, identifying significant interactions atSTC1: SNPs had larger effects on eGFRcrea at higher TSH levels, possibly reflecting stanniocalcin-1 autocrine and paracrine role. Individual population studies can help characterize genetic associations. The interplay between phenotypes atSHROOM3andSLC34A1and the role of thyroid function as a genetic effect modifier warrant further investigations.

Genome-wide association studies have discovered hundreds of associations between common genotypes and kidney function but cannot comprehensively investigate rare coding variants. Here, we applied a genotype imputation approach to whole exome sequencing data from the UK Biobank to increase sample size from 166,891 to 408,511. We detected 158 rare variants and 105 genes significantly associated with one or more of five kidney function traits, including genes not previously linked to kidney disease in humans. The imputation-powered findings derive support from clinical record-based kidney disease information, such as for a novel splice allele in PKD2, and from functional studies of a novel frameshift allele in CLDN10. This cost-efficient approach boosts statistical power to detect and characterize both known and novel disease susceptibility variants and genes, can be generalized to larger future studies, and generates a comprehensive resource (https://ckdgen-ukbb.gm.eurac.edu/) to direct experimental and clinical studies of kidney disease.

Delay management for railways is concerned with the question of whether a train should wait for a delayed feeder train or depart on time. The answer should not only depend on the length of the delay but also consider other factors, such as capacity restrictions. We present an optimization model for delay management in railway networks that accounts for capacity constraints on the number of passengers that a train can effectively carry. While limited capacities of tracks and stations have been considered in delay management models, passenger train capacity has been neglected in the literature so far, implicitly assuming an infinite train capacity. However, even in open systems where no seat reservation is required and passengers may stand during the journey if all seats are occupied, physical space is naturally limited, and the number of standing seats is constrained for passenger safety reasons. We present a mixed-integer nonlinear programming formulation for the delay management problem with passenger rerouting and capacities of trains. Our model allows the rerouting of passengers missing their connection due to delays or capacity constraints. We linearize the model in exact and approximate ways and experimentally compare the different approaches with the solution of a reference model from the literature that neglects capacity constraints. The results demonstrate that there is a significant impact of considering train capacity restrictions in decisions to manage delays.

Passengers traveling by train may need to change trains on their route. If the focal train of a passenger is late, the passenger might miss his connection and has to decide how to continue his trip. Delay management addresses the question whether the connecting train should wait (or not) for the delayed passengers. If the connecting train waits, delays would get transferred through the network. In literature, several works consider delays and their impact on railways and how to reschedule disturbed plans. We focus on works, aiming to minimize passenger inconvenience as it is done in delay management. In the last two decades, dozens of works considering the delay management problem have emerged, tackling the problem in different ways. In this paper, an overview on the existing literature is given, and a new classification is introduced. We provide a taxonomy scheme for railway problems at an operational level and show how the field of delay management fits to other parts of the planning process. Moreover, limitations of the delay management approaches are discussed and future research opportunities are suggested.

Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro‐adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low‐density lipoprotein (oxLDL)‐dependent activation of PPARγ, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient‐derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARγ upregulation. By boosting oxLDL in a Pkp2 heterozygous knock‐out mice through high‐fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies., ACM mutations are necessary but not sufficient for disease penetrance. The contribution of oxidised lipids as novel pharmacologically targetable cofactors was demonstrated by a multi‐layer approach (patients – in vitro – in vivo), leading to an advancement in the knowledge of ACM pathogenesis.

Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson’s disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component. We performed an hypothesis-free whole-exome sequencing (WES)-based screening of time-to-LID onset and attempted replication of previously published candidate gene studies. A WES association analysis was carried out in 134 PD patients in a meta-analytical framework. Replication was attempted in an independent study of 97 PD patients. Variants from previously reported candidate genes (OPRM1, COMT, BDNF) were also specifically examined. We significantly replicated, for the first time, an association of variant rs1799971 in the OPRM1 gene with time-to-LID onset. Furthermore, we identified two novel potentially functional variants, in the MAD2L2 (rs2233019) and MAP7 (rs35350783) genes, which were significantly associated at the discovery stage. In the replication study, the two variants showed direction-consistent effects but did not achieve the replication significance threshold. Our study provides the first WES results for time-to-LID onset, where we replicate association at OPRM1, and suggest new variants in MAD2L2 and MAP7 genes that are significant in discovery, but require larger datasets for replication. The results are being made publicly available to allow for independent external validation.

Railway delay management considers the question of whether a train should wait for a delayed feeder train. Several works in the literature analyze these so-called wait-depart decisions. The underlying models range from rules of thumb to complete network optimizations. Almost none of them account for uncertainties regarding future delays. In this paper, we present a multi-stage stochastic dynamic programming (SDP) model to make wait-depart decisions in the presence of uncertain future delays. The SDP approach explicitly accounts for potential recourse actions at later stations in a look-ahead manner when making the decision in the current stage. The objective is to minimize the total delay experienced by passengers at their final station by recursively solving Bellman equations. We focus on a single train line but consider the effects on direct feeder and connecting trains. In an extensive numerical study, we compare the solution quality and computational effort of the SDP to other optimization approaches and simple heuristic decision rules that are frequently used in delay management. The SDP approach outperforms the other approaches in almost every scenario with regard to solution quality in reasonable time and seems to be a promising starting point for stochastic dynamic delay management with interesting future research opportunities.

Purpose Mutations in SZT2 have been previously reported in several cases of early onset epilepsy and intellectual disability. In this study we investigate potential causal mutations in two male siblings affected by early onset epilepsy, intellectual disability and macrocephaly. Methods We use family-based whole-exome sequencing to identify candidate variants. Results We report the identification of two potential causal SZT2 mutations in compound heterozygous state. We observe considerable differences in the clinical phenotype severity of the two affected individuals. The cerebral MRI revealed no abnormalities in the older affected brother, while in the youngest one it revealed a right frontal polymicrogiria. Moreover, while good seizure control was achieved in the older affected individual the younger brother is affected by pharmacoresistant epilepsy, progressive spastic paraplegia, cortical myoclonus and a more severe intellectual disability. We also analyzed the relative location of the reported pathogenic mutations in the SZT2 protein. Conclusion Variable phenotypic expressivity is observed for this condition, while the location and type of mutations in SZT2 also has a potential impact on epilepsy severity. These findings extend our knowledge of epileptogenic conditions related to SZT2 and mTOR signaling.

Background Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. Methods We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. Results We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein’s only serine kinase domain. Conclusions In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model. Electronic supplementary material The online version of this article (10.1186/s12881-017-0503-7) contains supplementary material, which is available to authorized users.

Background During the last decade, a great number of extremely valuable large-scale genomics and proteomics datasets have become available to the research community. In addition, dropping costs for conducting high-throughput sequencing experiments and the option to outsource them considerably contribute to an increasing number of researchers becoming active in this field. Even though various computational approaches have been developed to analyze these data, it is still a laborious task involving prudent integration of many heterogeneous and frequently updated data sources, creating a barrier for interested scientists to accomplish their own analysis. Results We have implemented Dintor, a data integration framework that provides a set of over 30 tools to assist researchers in the exploration of genomics and proteomics datasets. Each of the tools solves a particular task and several tools can be combined into data processing pipelines. Dintor covers a wide range of frequently required functionalities, from gene identifier conversions and orthology mappings to functional annotation of proteins and genetic variants up to candidate gene prioritization and Gene Ontology-based gene set enrichment analysis. Since the tools operate on constantly changing datasets, we provide a mechanism to unambiguously link tools with different versions of archived datasets, which guarantees reproducible results for future tool invocations. We demonstrate a selection of Dintor’s capabilities by analyzing datasets from four representative publications. The open source software can be downloaded and installed on a local Unix machine. For reasons of data privacy it can be configured to retrieve local data only. In addition, the Dintor tools are available on our public Galaxy web service at http://dintor.eurac.edu. Conclusions Dintor is a computational annotation framework for the analysis of genomic and proteomic datasets, providing a rich set of tools that cover the most frequently encountered tasks. A major advantage is its capability to consistently handle multiple versions of tool-associated datasets, supporting the researcher in delivering reproducible results. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-2279-5) contains supplementary material, which is available to authorized users.

Background Although several methods have been proposed for predicting the effects of genetic variants and their role in disease, it is still a challenge to identify and prioritize pathogenic variants within sequencing studies. Methods Here, we compare different variant and gene-specific features as well as existing methods and investigate their best combination to explore potential performance gains. Results We found that combining the number of “biological process” Gene Ontology annotations of a gene with the methods PON-P2, and PROVEAN significantly improves prediction of pathogenic variants, outperforming all individual methods. A comprehensive analysis of the Gene Ontology feature suggests that it is not a variant-dependent annotation bias but reflects the multifunctional nature of disease genes. Furthermore, we identified a set of difficult variants where different prediction methods fail. Conclusion Existing pathogenicity prediction methods can be further improved.

The Romance of the Forest shows a girl in the grip of the stern world of the Symbolic order. Although she accepts the Symbolic order itself, she rejects her place in it. Adeline does not understand this world because it does not satisfy her inmost needs as a human being. Therefore, her Family Romance aims at changing her place and thus her destiny in the social order. She experiences her story as an utter loss of plenitude following the death of the woman she believes to be her mother when she is aged seven. However, she is not aware of a prior experience of plenitude and its loss with regard to her biological mother, whose death precipitates all the disastrous developments in her family. Wealthy and high-ranking, her biological family was indeed a site of originary plenitude. Adeline’s first, irrecoverable loss of plenitude, her originary trauma, is the death of her mother and the subsequent murder of her father. These events also cause her dislocation from the happy family and from her high station in life — loss of plenitude coded as loss of place.

Evelina purports to be The History of A Young Lady’s Entrance into the World; that is to say, the story of her entrance into the Symbolic order that confers identity on its subjects. However, this entrance is exacerbated by problems attending the young lady’s identity. Thus, this novel is about the terms and conditions under which an individual may enter the symbolic order as a subject. Evelina is about a disowned and dispossessed daughter’s identity and her path to attain her social and symbolic place. As a child’s identity consists of both a physical and a socio-symbolic component, of a material body and a name, Evelina is also about the question of what kind of identity a mother and father confer on a child. In Evelina, a battle rages over parental authority against the background of diminishing maternal authority in the late eighteenth-century cultural domain, yet mothers and maternal figures do not give up their authority without a fight. Thus, in Evelina patriarch(y) and matriarch(y) fight for authority.

In the eighteenth century, courtship is seen as the only authorized cultural activity that gives women power in patriarchal society. Thus, the figure of the wealthy orphaned coquette allows authors to explore questions of authority, imprudent behaviour, the dangers to which the heroine is exposed and the true relations of power that obtain in the family and in patriarchy. The novels with which I am about to deal feature a rich young woman who has lost both parents before the age of majority. Betsy Thoughtless and Miss Milner are of good family and have a large enough fortune to think well of their place in society. But most importantly, they think highly of their personal charms and expect society to admire them. In the world of courtship this expectation may be reasonable, but in other social affairs the coquette must be given a rude awakening to the power that society has over them. The orphaned coquettes experience no parental pressure and, though they protest their obedience to their appointed guardians, in reality they rarely heed the latters’ advice or admonitions. Coquettes remain incorrigible until it is (almost) too late. The last sentence of A Simple Story spells out that society’s primary concern with coquettes is their defective education in feminine submission.

Although not a coquette, Arabella, the heroine of Charlotte Lennox’s The Female Quixote, craves an empire of women, especially with regard to men’s hearts. Even more important to her story is her capacity to imagine and enact stories in which she herself is the centre of attention. Her fantasy of an unconditional subjection of men and a world where women wield absolute power can be explained with recourse to Lacan’s notion of desire. Arabella’s notions are the opposite of the power relations that obtain in eighteenth-century society: she desires and in her imagination she appropriates for women what men have; that is to say, power. Such power is defined in psychoanalysis as the phallus, ‘the signifier of that which is worthy of desire’, but it is important to bear in mind that the signifier of desire is not the same as the cause of desire, which remains beyond signification. Object (a), the real cause of desire, is unspeakable, while the phallus, ‘the name of desire’, is pronounceable.1 In Arabella’s story, the name of desire is the empire of women, while the cause of desire is her mother. Her mother died when Arabella was born, thus her absence represents a lack for Arabella; ‘Insofar as desire is always correlated with lack, the phallus is the signifier of lack.’2 Thus, Arabella’s fantasy of female power, her phallus so to speak, is in fact the signifier of the lack that she unconsciously experiences. Although her mother is not signified — she is only a trace in the narrative — she seems to exert a power from beyond the grave.

Although Jane Austen’s work is deeply influenced by eighteenth-century literature, especially fiction, she also breaks the mould provided by her predecessors. Austen picks up the themes of earlier novels and in her turn reimagines the novel as a genre. A voracious and unashamed reader of novels, she is well placed at the turn of the century to make her own contribution. As my analysis of Emma has shown, Austen reworks the notions of the orphaned heiress and the quixotic reader with a particular class perspective and social regeneration in mind. Likewise, Persuasion shows the influence of previous novels about orphans, but also changes the orphan paradigms that Austen inherits from her predecessors. Numerous eighteenth-century novels about orphans urge the necessity of feminine submission to the Law-of-the-Father, or depict the consequences deriving from it. Anne belongs to the category of heroines who have bowed to the symbolic order. Persuasion is akin to Charlotte Smith’s Emmeline in pointing out the necessity to question paternal authority or to Radcliffe’s matriarchal novels in the need to rebel against it. Austen does this by reversing the normal course of events: Anne ‘had been forced into prudence in her youth, she learned romance as she grew older — the natural sequel of an unnatural beginning’ (30).1 If the eighteenth century insists on the subjection and repression of woman as prerequisite to the normal functioning of the social order, Austen directs attention to the utter waste of human potential produced by the acceptance of this requirement.

Through the protagonist of her first novel, Charlotte Smith can enact a fantasy of female empowerment within the Symbolic order rather than outside it, as was the case with orphaned heiresses. Since this idea strains against the prevailing notions of feminine decorum and propriety, her protagonist must both be impeccable in her behaviour and yet become increasingly self-assertive as the narrative develops. Emmeline Mowbray is the neglected and possibly illegitimate orphan of Mowbray castle. She is marginalized not only by being branded as illegitimate, but also by her physical distance in the remote Welsh castle where she grows up. She is besieged by suitors and repulsed by dishonest, avaricious patriarchs. Both of these patriarchal representatives (the younger and the older generation) force her to conform to their wishes. Torn between their incompatible demands and constrained by their coercive measures, she slowly discovers ways to attain her own desires. Emmeline must overcome her assumed status as an object of patriarchal discourse and desire, and learn to act as a subject with legitimate desires of her own. The process of assuming a subject position is enacted partly in her relationship to Mowbray castle and especially in her relation to her biological family. These two entities are closely linked to the Symbolic order and the way it envisions the daughter’s place within it. As such, the story of Emmeline’s assumption of agency is also a sharp-eyed critique and demystification of the power relations that obtain in eighteenth-century patriarchal Britain.

A Sicilian Romance closes with a female community whose members are also tied to each other by family bonds. In The Italian, Radcliffe extends the female circle to include other like-minded women, as if to overturn the status quo of women’s relation to each other in patriarchy. Irigaray emphasizes the ‘one thing that has been singularly neglected, barely touched upon, in the theory of the unconscious: the relation of woman to the mother and the relation of women among themselves’.1 Although (patriarchal) psychoanalysis may have neglected this area of the psyche, Radcliffe is intent on exploring it. In The Italian, she is interested in the mother-daughter bond primarily as a bond between women. The nun Olivia, particularly through her singing and her voice, strikes a particular chord in Ellena that will later be explained as the cri du sang attracting daughter to mother. Yet the plot is so contrived that their blood relation is concealed while the two women establish their friendship. In this novel, the mother will retain her independence by remaining in the convent of Santa Maria della Pieta. Thus, Radcliffe valorizes the female bond over the blood relationship of the two women. In an age when women were increasingly reduced to their reproductive role, though utterly deprived of any rights as mothers, Radcliffe daringly depicts ‘women among themselves’ in her portrait of two convents. Patriarchy stifles both mother’s and daughter’s possibilities of expression, while the oedipal logic requires the daughter to sever herself from her maternal origins.

Irigaray argues that the female body is represented as a lack or atrophy by phallogocentric discourse.1 This lack or atrophy is represented openly in A Sicilian Romance as a result of the patriarchal suffocation of women’s desires and selves. As soon as women take matters into their own hands, this lack can be eliminated and new perspectives open up, both for the heroine and society as a whole. Radcliffe explores in fictional form what Irigaray later theorizes: ‘their fatherland, family home, discourse, imprison us [women] in enclosed spaces where we cannot keep on moving, living, as ourselves’, so how can we ‘[d]isengage ourselves, alive, from their concepts’ and achieve the positive revaluation of the feminine?2 Radcliffe’s novel explores the nature of patriarchy and the male unconscious, its effects on women and children, as well as possible resistance to it.

As we have seen in Chapter 7, Lennox’s heiress Arabella is forced to give up the romance to eliminate the threat of a woman who can fulfil her fantasies of female power. It was Horace Walpole who ‘resuscitated’ the romance genre with his 1764 tale and returned readers to the heiress’s claims obliquely, but using a different aesthetic strategy. As a young man, Walpole was an avid reader of chivalric romances, while in adulthood he had a mansion constructed in the Gothic manner and as a collector of antique artefacts he was immersed in his culture’s obsession with the mediaeval past (the so-called Gothic revival). The story has it that following a nightmare he had one night in his Gothic mansion, Walpole began to write The Castle of Otranto ‘surrounded by old tomes and suits of armour, the light filtering through stained-glass windows’.1 Arguably, as the product of such a nightmare, The Castle of Otranto feels and works like a dream. Yet it is doubtful which diegetic character’s dream it is. Is it Manfred’s nightmare in which he can confront the terrifying fear of retribution or Theodore’s wish-fulfilment fantasy?

Elizabeth Inchbald’s coquette follows an utterly tragic trajectory. In many ways similar to Betsy, in one crucial aspect Miss Milner is different: she does not remain faithful to her husband, who does not gratify her narcissistic ego after marriage. Rather, she voluntarily commits adultery, whereas in Betsy’s story it is Mr Munden who does so. Narcissism is better suited to describe Miss Milner’s relations with men, although at first it seems that she has an anaclitic object choice, potentially modelled on her own father, who appointed Dorriforth/Elmwood as her guardian. If we do insist that she has an anaclitic object choice, then this novel can be taken as an instance of Lacan’s idea that there is no sexual relation. Each of the protagonists is caught in a different kind of love story, unwilling to give up their imaginary identifications and desires.

Evelina depicts the failings of the most prominent representatives of patriarchy, but it draws back from the open critique of the institution itself. The father figure is cleared of wilful negligence or cruelty towards his daughter, and the blame is laid entirely at the door of the lowest class, represented in the figure of the nurse. Inchbald’s novel is more radical. If Evelina is unnecessarily terrified of the sight of her father, Inchbald’s father figure appears truly terrifying, ‘an unmasked version of the figure of authority’ in a radically different world.1 Between the appearance of the two novels a cataclysmic event across the Channel shook the world, which may have contributed to the way in which Inchbald conceived the second half of her novel, depicting the life of her coquettish heroine’s daughter. Scholars assume that the novel was originally conceived in the 1770s and was redesigned and extended in 1789–90.2 By 1791, the figure of the despotic patriarch had become de rigueur. This same year saw the publication of Radcliffe’s The Romance of the Forest and Charlotte Smith’s Celestina, both of which draw very critical pictures of patriarchal tyranny. Part 1 of A Simple Story focuses on the rebellious figure of the coquette, while Part 2, perhaps influenced by the political events following the French Revolution, offers a totally different story. The two generations of this novel truly live in different eras. This is frequently alluded to in the text itself, nowhere as clearly as at the end, in its moral: the reader ‘has beheld the pernicious effects of an improper education in the destiny which attended the unthinking Miss Milner.

Mary Hays’ radical novel could be allocated to other parts of this book, as it has a particular resonance with Defoe’s Moll Flanders and with Gothic fiction. However, it works remarkably well as the third book regarding the gradual subjection of woman’s will. These three novels by Burney, Inchbald and Hays form an increasingly gloomy trilogy, culminating in the death of Hays’ heroine. All three authors are interested in the question of women’s education and its consequences for women’s lives. It is conceived positively in the first two: Evelina’s cultural capital secures her the love of a lord and Matilda’s self-abnegation allows her to soften her father’s heart. All three are interested in the daughter’s relation to and her need to distance herself from her mother. They also explore woman’s relation to the Symbolic order and her place(ability) in it. Evelina has the happiest fate of these heroines; Lady Matilda’s happiness is questionable; but Mary Hays shows that under the restrictive code of femininity, the heroine can only fail and die. In her fiercely political novel, Mary Hays confronts the problems of her age head on and frankly points out that there is no consolation to be found for women: impeccable virtue and a gentlewoman’s education will not buy the orphan a place in society. Whether we interpret the heroine’s death as the symbolic death of her selfhood, of her independent spirit or as the actual death of her body and with that of everything, the point is clear: the sins of the mother cannot be escaped, the Law-of-the-Father is implacable regarding women, and defenceless orphaned daughters are doomed.

Frances Burney conceives of her second novel Cecilia as a kind of profit-and-loss account, pitting female jouissance against the castrating Name-of-the-Father. The disempowerment of the eponymous heroine is played out literally in economic terms, because, Burney makes no bones about it, depriving the heroine of her money is tantamount to taking away her treasured agency. Virginia H. Cope argues that Cecilia’s identity is not lost in the process, that it can ‘survive the loss of its material supports’.1 However, given Cecilia’s psychical investment in and construction of her identity as an agent of charity, I argue that it cannot survive intact but has to mutate into an identity that is compatible with patriarchal norms.

(1994). Haushalt und Familie in San Juan de Yapacani, einer japanischen Auswanderer-Kolonie in Bolivien. Japanstudien: Vol. 5, No. 1, pp. 311-339.

Damit war bewiesen, das die genannten, von Pilzen ausgeschiedenen organischen Sauren die Rohphosphate als Phosphatquelle erschliesen konnen, auf die dann auch die nicht saurebildenden Bodenpilze, chemotropisch reagieren.