The Detection of Foreign Items in Laundry Industry by Dual-Energy X-ray Transmission-Advantages and Limits.

Firefighters, paramedics, nursing staff, and other occupational groups are in constant need of fast and proper cleaning of their professional workwear, not only during a pandemic. Thus, laundry technology needs to become more efficient and automated. Unfortunately, some steps of the cleaning process, such as finding and removing foreign items from pockets or belts, are still completed manually. This is not just time-consuming but potentially dangerous for the workers due to the hazardous nature of items such as scissors, scalpels, or syringes. Additionally, some items may damage the garments by staining or harm the laundry machines, causing malfunctions and process failure. On the one hand, these foreign items are often hidden inside the clothes, making detection very challenging with conventional superficial sensors. On the other hand, these items can be diverse and cannot be detected by metal detectors alone. X-ray transmission has proven to be a powerful tool for detecting items inside of objects. The dual-energy approach (DE-XRT) even allows obtaining quantitative information about the chemical composition of the measured materials. In this study, working garments were accompanied and filled with realistic foreign items. The potential of DE-XRT to detect those items was successfully shown.

Fairness in Music Recommender Systems: A Stakeholder-Centered Mini Review.

The performance of recommender systems highly impacts both music streaming platform users and the artists providing music. As fairness is a fundamental value of human life, there is increasing pressure for these algorithmic decision-making processes to be fair as well. However, many factors make recommender systems prone to biases, resulting in unfair outcomes. Furthermore, several stakeholders are involved, who may all have distinct needs requiring different fairness considerations. While there is an increasing interest in research on recommender system fairness in general, the music domain has received relatively little attention. This mini review, therefore, outlines current literature on music recommender system fairness from the perspective of each relevant stakeholder and the stakeholders combined. For instance, various works address gender fairness: one line of research compares differences in recommendation quality across user gender groups, and another line focuses on the imbalanced representation of artist gender in the recommendations. In addition to gender, popularity bias is frequently addressed; yet, primarily from the user perspective and rarely addressing how it impacts the representation of artists. Overall, this narrative literature review shows that the large majority of works analyze the current situation of fairness in music recommender systems, whereas only a few works propose approaches to improve it. This is, thus, a promising direction for future research.

Support the underground: characteristics of beyond-mainstream music listeners.

Music recommender systems have become an integral part of music streaming services such as Spotify and Last.fm to assist users navigating the extensive music collections offered by them. However, while music listeners interested in mainstream music are traditionally served well by music recommender systems, users interested in music beyond the mainstream (i.e., non-popular music) rarely receive relevant recommendations. In this paper, we study the characteristics of beyond-mainstream music and music listeners and analyze to what extent these characteristics impact the quality of music recommendations provided. Therefore, we create a novel dataset consisting of Last.fm listening histories of several thousand beyond-mainstream music listeners, which we enrich with additional metadata describing music tracks and music listeners. Our analysis of this dataset shows four subgroups within the group of beyond-mainstream music listeners that differ not only with respect to their preferred music but also with their demographic characteristics. Furthermore, we evaluate the quality of music recommendations that these subgroups are provided with four different recommendation algorithms where we find significant differences between the groups. Specifically, our results show a positive correlation between a subgroup's openness towards music listened to by members of other subgroups and recommendation accuracy. We believe that our findings provide valuable insights for developing improved user models and recommendation approaches to better serve beyond-mainstream music listeners.

Potential of Dual and Multi Energy XRT and CT Analyses on Iron Formations.

Dual and multi energy X-ray transmission imaging (DE-/ME-XRT) are powerful tools to acquire quantitative material characteristics of diverse samples without destruction. As those X-ray imaging techniques are based on the projection onto the imaging plane, only two-dimensional data can be obtained. To acquire three-dimensional information and a complete examination on topology and spatial trends of materials, computed tomography (CT) can be used. In combination, these methods may offer a robust non-destructive testing technique for research and industrial applications. For example, the iron ore mining and processing industry requires the ratio of economic iron minerals to siliceous waste material for resource and reserve estimations, and for efficient sorting prior to beneficiation, to avoid equipment destruction due to highly abrasive quartz. While XRT provides information concerning the thickness, areal density and mass fraction of iron and the respective background material, CT may deliver size, distribution and orientation of internal structures. Our study shows that the data provided by XRT and CT is reliable and, together with data processing, can be successfully applied for distinguishing iron oxide rich parts from waste. Furthermore, heavy element bearing minerals such as baryte, uraninite, galena and monazite can be detected.

Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved. METHODS: We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory. RESULTS: A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy. CONCLUSION: We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT.

Listener Modeling and Context-Aware Music Recommendation Based on Country Archetypes.

Music preferences are strongly shaped by the cultural and socio-economic background of the listener, which is reflected, to a considerable extent, in country-specific music listening profiles. Previous work has already identified several country-specific differences in the popularity distribution of music artists listened to. In particular, what constitutes the "music mainstream" strongly varies between countries. To complement and extend these results, the article at hand delivers the following major contributions: First, using state-of-the-art unsupervized learning techniques, we identify and thoroughly investigate (1) country profiles of music preferences on the fine-grained level of music tracks (in contrast to earlier work that relied on music preferences on the artist level) and (2) country archetypes that subsume countries sharing similar patterns of listening preferences. Second, we formulate four user models that leverage the user's country information on music preferences. Among others, we propose a user modeling approach to describe a music listener as a vector of similarities over the identified country clusters or archetypes. Third, we propose a context-aware music recommendation system that leverages implicit user feedback, where context is defined via the four user models. More precisely, it is a multi-layer generative model based on a variational autoencoder, in which contextual features can influence recommendations through a gating mechanism. Fourth, we thoroughly evaluate the proposed recommendation system and user models on a real-world corpus of more than one billion listening records of users around the world (out of which we use 369 million in our experiments) and show its merits vis-à-vis state-of-the-art algorithms that do not exploit this type of context information.

Global and country-specific mainstreaminess measures: Definitions, analysis, and usage for improving personalized music recommendation systems.

RELEVANCE: Popularity-based approaches are widely adopted in music recommendation systems, both in industry and research. These approaches recommend to the target user what is currently popular among all users of the system. However, as the popularity distribution of music items typically is a long-tail distribution, popularity-based approaches to music recommendation fall short in satisfying listeners that have specialized music preferences far away from the global music mainstream. Addressing this gap, the contribution of this article is three-fold. DEFINITION OF MAINSTREAMINESS MEASURES: First, we provide several quantitative measures describing the proximity of a user's music preference to the music mainstream. Assuming that there is a difference between the global music mainstream and a country-specific one, we define the measures at two levels: relating a listener's music preferences to the global music preferences of all users, or relating them to music preferences of the user's country. To quantify such music preferences, we define a music item's popularity in terms of artist playcounts (APC) and artist listener counts (ALC). Moreover, we adopt a distribution-based and a rank-based approach as means to decrease bias towards the head of the long-tail distribution. This eventually results in a framework of 6 measures to quantify music mainstream. DIFFERENCES BETWEEN COUNTRIES WITH RESPECT TO MUSIC MAINSTREAM: Second, we perform in-depth quantitative and qualitative studies of music mainstream in that we (i) analyze differences between countries in terms of their level of mainstreaminess, (ii) uncover both positive and negative outliers (substantially higher and lower country-specific popularity, respectively, compared to the global mainstream), analyzing these with a mixed-methods approach, and (iii) investigate differences between countries in terms of listening preferences related to popular music artists. We conduct our studies and experiments using the standardized LFM-1b dataset, from which we analyze about 800,000,000 listening events shared by about 53,000 users (from 47 countries) of the music streaming platform Last.fm. We show that there are substantial country-specific differences in listeners' music consumption behavior with respect to the most popular artists listened to. RATING PREDICTION EXPERIMENTS: Third, we demonstrate the applicability of our study results to improve music recommendation systems. To this end, we conduct rating prediction experiments in which we tailor recommendations to a user's level of preference for the music mainstream using the proposed 6 mainstreaminess measures: defined by a distribution-based or rank-based approach, defined on a global level or on a country level (for the user's country), and for APC or ALC. Our approach roughly equals a hybrid recommendation approach in which a demographic filtering strategy is implemented before collaborative filtering is performed. Results suggest that, in terms of rating prediction accuracy, each of the presented mainstreaminess definitions has its merits.

Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking. OBJECTIVE: This study investigated a priori hypotheses on specific effects of prefrontal-tDCS montages by using multimodal functional magnetic resonance imaging (fMRI) in healthy participants. METHODS: 28 healthy male participants underwent three common active-tDCS montages and sham tDCS in a pseudo-randomized order, comprising a total of 112 tDCS-fMRI sessions. Active tDCS was applied at 2 mA for 20 min. Before and after tDCS, a resting-state fMRI (RS fMRI) was recorded, followed by a task fMRI with a delayed-response working-memory (DWM) task for assessing cognitive control over emotionally negative or neutral distractors. RESULTS: After tDCS with a cathode-F3/anode-F4 montage, RS-fMRI connectivity decreased in a medial part of the left PFC. Also, after the same stimulation condition, regional brain activity during DWM retrieval decreased more in this area after negative than after neutral distraction, and responses to the DWM task were faster, independent of distractor type. CONCLUSION: The current study does not confirm our a priori hypotheses on direction and localization of polarity-dependent tDCS effects using common bipolar electrode montages over PFC regions, but it provides evidence for montage-specific effects on multimodal neurophysiological and behavioral outcome measures. Systematic research on the actual targets and the respective dose-response relationships of prefrontal tDCS is warranted.

Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies.

Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.

Resolving Bottlenecks: Converting Three High-Enrollment Nursing Courses to an Online Format.

BACKGROUND: Converting large undergraduate classes from the classroom to online has been an effective way to increase enrollments in high-demand courses in undergraduate education. However, challenges exist to maintaining students' high-quality learning interaction and engagement in large online courses. This article presents a collaborative model between faculty in health sciences and instructional designers to redesign and redevelop three high-enrollment courses to online at Boise State University. METHOD: Health studies course faculty and eCampus instructional designers conducted this study to reflect the collaborative online course development process at Boise State. RESULTS: The offering of high-enrollment nursing courses met enrollment demand and maintained student retention. Challenges related to instruction were addressed by using a careful course redesign process and continuous improvement. CONCLUSION: Implications of this educational innovation for health science educators, instructional designers, and lessons learned are provided.

Epithelial deletion of podoplanin is dispensable for re-epithelialization of skin wounds.

The mucin-like transmembrane protein podoplanin (PDPN) is prominently represented in tumor-associated gene expression signatures of numerous types of cancer including squamous cell carcinoma, and gain-of-function and knockdown approaches in tissue culture strongly suggested an important role of PDPN in cell proliferation, migration and adhesion. PDPN is absent during epidermal homeostasis but is highly expressed in basal keratinocytes during cutaneous wound healing. Enhanced motility of immortalized keratinocytes upon ectopic PDPN overexpression argues for wound healing defects upon podoplanin deficiency in keratinocytes; however, in vivo data that unequivocally define the impact of PDPN by functional studies in a physiologically relevant system are still missing. Here, we have applied an in vivo loss-of-function approach by generating a novel transgenic mouse line with keratinocyte-specific podoplanin deficiency. Performing cutaneous full-thickness excisional wounds to examine re-epithelialization capacity, unexpectedly, no defects were observed in wound healing properties of mutant mice. Similarly, PDPN-deficient primary keratinocytes showed no impairment in migration, adhesion or proliferation. Thus, PDPN function is not rate-limiting for re-epithelialization but may be functionally compensated by an as yet unknown protein. Our data also call for in vivo functional studies on PDPN in settings of skin tumor development and progression to clarify PDPN's role in skin pathology.

Efficient keratinocyte differentiation strictly depends on JNK-induced soluble factors in fibroblasts.

Previous studies demonstrated that fibroblast-derived and JUN-dependent soluble factors have a crucial role on keratinocyte proliferation and differentiation during cutaneous wound healing. Furthermore, mice with a deficiency in Jun N-terminal kinases (JNKs) , JNK1 or JNK2, showed impaired skin development and delayed wound closure. To decipher the role of dermal JNK in keratinocyte behavior during these processes, we used a heterologous coculture model combining primary human keratinocytes and murine fibroblasts. Although cocultured JNK1/JNK2-deficient fibroblasts did not affect keratinocyte proliferation, temporal monitoring of the transcriptome of differentiating keratinocytes revealed that efficient keratinocyte differentiation not only requires the support by fibroblast-derived soluble factors, but is also critically dependent on JNK1 and JNK2 signaling in these cells. Moreover, we showed that the repertoire of fibroblast transcripts encoding secreted proteins is severely disarranged upon loss of JNK under the coculture conditions applied. Finally, our data demonstrate that efficient keratinocyte terminal differentiation requires constant presence of JNK-dependent and fibroblast-derived soluble factors. Taken together, our results imply that mesenchymal JNK has a pivotal role in the paracrine cross talk between dermal fibroblasts and epidermal keratinocytes during wound healing.

Hepatocyte-specific S100a8 and S100a9 transgene expression in mice causes Cxcl1 induction and systemic neutrophil enrichment.

BACKGROUND: Calprotectin consists of the Ca2+-binding proteins S100a8 and S100a9 that are induced in epithelial cells in response to tissue damage and infection. Both proteins are also secreted by activated innate immune cells and numerous studies demonstrate their crucial role in pathological conditions of acute and chronic inflammation. RESULTS: Here, we established a conditional mouse model with simultaneous S100a8 and S100a9 transgene expression in hepatocytes (TgS100a8a9hep) under the control of doxycycline to unravel the role of epithelial-derived Calprotectin on tissue homeostasis and inflammation. TgS100a8a9hep mice displayed a significant enrichment of neutrophils in peripheral blood and tissues with high blood content. Interestingly, Cxcl1 transcription was significantly induced in the liver of TgS100a8a9hep mice and primary hepatocytes derived thereof as compared to Control mice, accompanied by an increase of Cxcl1 serum levels. However, expression of other chemokines with a known function in neutrophil mobilization from the bone marrow, e.g. Csf3 and Cxcl2, was not altered. Doxycycline treatment of TgS100a8a9hep mice reduced Cxcl1 expression in the liver and resulted in normal numbers of neutrophils. CONCLUSION: In summary, our data demonstrate for the first time that hepatocyte-specific S100a8 and S100a9 expression induces a systemic mobilization of neutrophils by a specific activation of Cxcl1 transcription in the liver.

Sample pooling obscures diversity patterns in intertidal ciliate community composition and structure.

The aim of this study was to assess the effect of sample pooling on the portrayal of ciliate community structure and composition in intertidal sediment samples. Molecular ciliate community profiles were obtained from nine biological replicates distributed in three discrete sampling plots and from samples that were pooled prior to RNA extraction using terminal restriction fragment polymorphism (T-RFLP) analyses of SSU rRNA. Comparing the individual replicates of one sampling plot with each other, we found a differential variability among the individual biological replicates. T-RFLP profiles of pooled samples displayed a significantly different community composition compared with the cumulative individual biological replicate samples. We conclude that sample pooling obscures diversity patterns in ciliate and possibly also other microbial eukaryote studies. However, differences between pooled samples and replicates were less pronounced when community structure was analyzed. We found that the most abundant T-RFLP peaks were generally shared between biological replicates and pooled samples. Assuming that the most abundant taxa in an ecosystem under study are also the ones driving ecosystem processes, sample pooling may still be effective for the analyses of ecological key players.

Gastric prolapse with pseudocysts following laparoscopic adjustable gastric banding.

INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) is a reversible method of surgical gastric restriction. Following LAGB, the adverse event most commonly necessitating subsequent reoperation is prolapse of the gastric corpus or fundus above the band. A review of the medical literature reveals no reports of nonpancreatic pseudocysts being associated with this adverse event. Nonpancreatic pseudocysts, encountered during revisional bariatric surgery should be considered a cause of irreducible gastric prolapse. CASE REPORT: We report the case of a 41-year-old Caucasian female who underwent laparoscopic surgery to revise an adjustable gastric band and to repair an anterior gastric prolapse. Intraoperatively, 2 pseudocysts were found on the gastric fundus above the band in association with the gastric prolapse. The pseudocysts were resected, the gastric prolapse was reduced, and the band was left in place. The patient recovered uneventfully. CONCLUSION: Nonpancreatic pseudocysts may be associated with gastric prolapse in patients who have undergone LAGB. These pseudocysts can often be excised laparoscopically without violating the gastric lumen. This atypical presentation of gastric prolapse may pose a diagnostic and therapeutic challenge as these patients may.

Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy.

INTRODUCTION: Neuropsychological abnormalities in transsexual patients have been reported in comparison with subjects without gender identity disorder (GID), suggesting differences in underlying neurobiological processes. However, these results have not consistently been confirmed. Furthermore, studies on cognitive effects of cross-sex hormone therapy also yield heterogeneous results. AIM: We hypothesized that untreated transsexual patients differ from men without GID in activation pattern associated with a mental rotation task and that these differences may further increase after commencing of hormonal treatment. METHOD: The present study investigated 11 male-to-female transsexual (MFTS) patients prior to cross-sex hormone therapy and 11 MFTS patients during hormone therapy in comparison with healthy men without GID. Using functional magnetic resonance imaging at 3-Tesla, a mental rotation paradigm with proven sexual dimorphism was applied to all subjects. Data were analyzed with SPM5. MAIN OUTCOME MEASURES: Patterns of brain activation associated with a mental rotation task. RESULTS: The classical mental rotation network was activated in all three groups, but significant differences within this network were observed. Men without GID exhibited significantly greater activation of the left parietal cortex (BA 40), a key region for mental rotation processes. Both transsexual groups revealed stronger activation of temporo-occipital regions in comparison with men without GID. CONCLUSIONS: Our results confirmed previously reported deviances of brain activation patterns in transsexual men from men without GID and also corroborated these findings in a group of transsexual patients receiving cross-sex hormone therapy. The present study indicates that there are a priori differences between men and transsexual patients caused by different neurobiological processes or task-solving strategies and that these differences remain stable over the course of hormonal treatment.

Frequent overexpression of the genes FXR1, CLAPM1 and EIF4G located on amplicon 3q26-27 in squamous cell carcinoma of the lung.

Previously, we reported gene amplification at chromosome 3q26-27 in more than one third of squamous cell carcinomas of the lung. Frequent amplification of eukaryotic translation initiation factor 4G on 3q27.1 indicated a possible role of this amplification in translation initiation. The analysis of 61 squamous cell lung carcinomas shows that the percentage of carcinomas with a 3q27.1 amplification increases in higher malignant tumors. Non-invasive (T1) and minimal-invasive (T2) tumor stages showed similar percentages of amplified and non-amplified tumors, whereas locally-invasive (T3) tumors revealed a statistically significant (p < 0.05) increased percentage of amplified tumors. Microarrays were used to analyze the expression pattern of genes mapping in the amplified domain and its flanking regions (3q25-28) as well as the expression of genes directly or indirectly associated with translation initiation in squamous cell carcinoma, large cell carcinoma, adenocarcinoma and small cell carcinoma. Three genes, namely FXR1, CLAPM1 and EIF4G, are most frequently overexpressed in the center of the amplified domain in squamous cell carcinomas. The eukaryotic translation initiation factors 4A1, 2B and 4B as well as the poly(A)-binding protein PABPC1 where found to be overexpressed in all lung cancer entities. We found, however, no overexpression of eIF4E. Our results contribute to the understanding of the frequent amplification processes in squamous cell carcinomas of the lung and to the understanding of the translation initiation that appears not to require eIF4E in lung carcinogenesis.

Meeting bariatric patient care needs: procedures and protocol development.

Regardless of whether your facility has an existing surgical bariatric program, ongoing attention to staff education and the organization's physical environment is key in identifying potential areas of risk and need for improvements in meeting the needs of this special patient population. Development of an organization-wide protocol specifically designed to meet the needs of all bariatric patients will facilitate the provision of safe and dignified care for both patient and caregiver. Protocol parameters to include are assessment for body mass index, abdominal-hip girth, mobility level, and skin complications. Assessment findings trigger care planning for optimal patient outcomes.

[Personality disorders after inpatient psychodynamic psychotherapy]. / Persönlichkeitsstörungen nach stationärer psychodynamischer Psychotherapie.

OBJECTIVES: The following paper presents the results of a post-treatment examination on inpatients with personality disorders who received psychodynamic psychotherapy. The examination was carried out approximately 3.3 years after the patients were discharged. METHODS: Of a group of 110 patients with personality disorders (ICD-10), 72 patients underwent follow-up examination. A comprehensive catamnesis was compiled for 59 former patients; 13 former patients answered by post. Treatment success was evaluated on the basis of the Symptom Checklist 90-R, Inventory of Interpersonal Problems and Questionnaire of Social Support. These surveys show no significant statistical difference between the data of the subgroups of participants and non-participants of the post-treatment examination at the start and end of therapy (Mann-Whitney-U-Test, p > 0.05). Treatment success was also examined using the Global Assessment of Functioning Scale, the Impairment-Score as well as an analysis of the patient's use of psychiatric and inpatient psychotherapeutic care and the medication received. RESULTS: Due to the reduction in general mental stress and interpersonal problems, and the increase in perceived social support, the patients showed a positive development. After being discharged 41% of the patients received outpatient psychotherapy without further psychiatric and inpatient psychotherapeutic care. CONCLUSIONS: The above results demonstrate that patients with personality disorders benefit from inpatient psychodynamic psychotherapy.

Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion-infected cells.

Prion diseases are neurodegenerative infectious disorders for which no prophylactic regimens are known. In order to induce antibodies/auto-antibodies directed against surface-located PrP(c), we used a covalently linked dimer of mouse prion protein expressed recombinantly in Escherichia coli. Employing dimeric PrP as an immunogen we were able to effectively overcome autotolerance against murine PrP in PrP wild-type mice without inducing obvious side effects. Treatment of prion-infected mouse cells with polyclonal anti-PrP antibodies generated in rabbit or auto-antibodies produced in mice significantly inhibited endogenous PrP(Sc) synthesis. We show that polyclonal antibodies are binding to surface-located PrP(c), thereby interfering with prion biogenesis. This effect is much more pronounced in the presence of full IgG molecules, which, unlike Fab fragments, seem to induce a significant cross-linking of surface PrP. In addition, we found immune responses against different epitopes when comparing antibodies induced in rabbits and PrP wild-type mice. Only in the auto-antibody situation in mice an immune reaction against a region of PrP is found that was reported to be involved in the PrP(Sc) conversion process. Our data point to the possibility of developing means for an active immunoprophylaxis against prion diseases.