Loss of heterozygosity of the von Hippel Lindau gene locus in polypoid dysplasia but not flat dysplasia in ulcerative colitis or sporadic adenomas

Carcinoma in ulcerative colitis (UC) develops from dysplastic precursor lesions, which include flat dysplasia (FD) and polypoid dysplasias (PD). PD may present as single or multiple polypoid structures or as plaque-like lesions that, independent of histological grade, are an indication for colectomy. PDs are histologically similar to adenomas and may not be readily distinguished by light microscopy. It is not known whether FD and PD are different entities, or whether they represent etiologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surrounding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK4A (9p16), and APC was also studied in 11 sporadic adenomas of the colon. LOH at the vHL locus was present in 50% of the samples of PD and in 12% of the samples of FD. LOH was seen in CC close to PD and FD in 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in FD in 42% cases and in CC close to PD and FD in 0% and 14% cases, respectively. LOH patterns between PD and FD of the markers for APC and 9p16 were not different. LOH in APC was seen in two of five cases of adenoma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrounding CC and involvement of p53 in HGD and CC in FD may represent genetic differences between the development of PD and FD and may be the cause of the different morphology. The infrequency of LOH at the vHL locus in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases.     

Development and validation of a Monte Carlo simulation of photon transport in an Anger camera

The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.     

Correction to: Where do university graduates live? – a computer vision approach using satellite images

Applied Intelligence - A Correction to this paper has been published: https://doi.org/10.1007/s10489-021-02433-z     

Traditional organizations and crisis management in transition—Organizational perspectives on new dynamics of independent civil engagement

Digitalization and the trend towards more short‐term and project‐oriented social engagement have had a direct impact on traditional crisis management. This societal change has supported the evolution of new types of volunteers who use low‐threshold potentials to organize and maintain support independently. Traditional institutions like the German Red Cross are challenged to deal with these rapid changes regarding their own organizational culture in relation to the new phenomenon of so‐called unaffiliated volunteers. This paper investigates how unaffiliated volunteers influence and change the organizational culture of German disaster management by analysing and reflecting organizational adaptation processes in the aftermath of the German floods in 2013, the storm events in the west of Germany in 2014 and the refugee relief mission in 2015–2016. Therefore, semi‐structured interviews with experts of the German Red Cross were held to analyse their reactions towards unaffiliated Volunteers during the Floods in 2013 and the refugee relief missions, and further focus group interviews were conducted to validate the extracted results. Findings suggest that among professionals and leading entities in the German Red Cross, a process of rethinking has emerged, recognizing the importance and necessity to open up organizational structures for the collaboration and coordination of unaffiliated volunteers.     

State-of-the-art of long-term preservation in product lifecycle management

Providing access to digital information for the indefinite future is the intention of long-term digital preservation systems. One application domain that certainly needs to implement such long-term digital preservation processes is the design and engineering industry. In this industry, products are designed, manufactured, and operated with the help of sophisticated software tools provided by product lifecycle management (PLM) systems. During all PLM phases, including geographically distributed cross-domain and cross-company collaboration, a huge amount of heterogeneous digital product data and metadata is created. Legal and economic requirements demand that this product data has to be archived and preserved for a long-time period. Unfortunately, the software that is able to interpret the data will become obsolete earlier than the data since the software and hardware lifecycle is relatively short-lived compared to a product lifecycle. Companies in the engineering industry begin to realize that their data is in danger of becoming unusable while the products are in operation for several decades. To address this issue, different academic and industrial initiatives have been initiated that try to solve this problem. This article provides an overview of these projects including their motivations, identified problems, and proposed solutions. The studied projects are also verified against a classification of important aspects regarding scope and functionality of digital preservation in the engineering industry. Finally, future research topics are identified.     

The residue of vector sets with applications to decidability problems in Petri nets

Summary A set K of integer vectors is called right-closed, if for any elementmK all vectors mm are also contained in K. In such a case K is a semilinear set of vectors having a minimal generating set res(K), called the residue of K. A general method is given for computing the residue set of a right-closed set, provided it satisfies a certain decidability criterion.Various right-closed sets wich are important for analyzing, constructing, or controlling Petri nets are studied. One such set is the set CONTINUAL(T) of all such markings which have an infinite continuation using each transition infinitely many times. It is shown that the residue set of CONTINUAL(T) can be constructed effectively, solving an open problem of Schroff. The proof also solves problem 24 (iii) in the EATCS-Bulletin. The new methods developed in this paper can also be used to show that it is decidable, whether a signal net is prompt [23] and whether certain -languages of a Petri net are empty or not.It is shown, how the behaviour of a given Petri net can be controlled in a simple way in order to realize its maximal central subbehaviour, thereby solving a problem of Nivat and Arnold, or its maximal live subbehaviour as well. This latter approach is used to give a new solution for the bankers problem described by Dijkstra.Since the restriction imposed on a Petri net by a fact [11] can be formulated as a right closed set, our method also gives a new general approach for implementations of facts.     

Traumatogenic factors affecting the knees of carpet installers

An ergonomics analysis of carpet installation tasks was performed. The purpose was to identify and quality potential sources of biomechanical trauma that may be responsible for the high rates of knee morbidity found by previous researchers among carpet layers. Nine carpet layers were studied either at an apartment building worksite or at a training school. Results from a job analysis indicated that workers spent approximatately 75% of their time in the kneeling position using a tool called a knee-kicker to stretch and install carpet. Awkward body postures were identified from films of workers installing carpets. At the moment of impact the knee is severely flexed, subtended angles were less than 60 degrees. To obtain measures of impact force on the knee, the kicker-tool was instrumented with a load cell. Workers who executed the hardest kicks with the tool produced impact peak forces that averaged 3019 newtons (N), which is equivalent to about four times body weight. Measures from an accelerometer attached to the worker's knee showed values in ecxess of 120 m/s², which are comparable to those found during vigorous running and jumping exercises. The results imply that repetitive impact of the knee joint from the use of the knee-kicker combined with knee flexion, kneeling and squatting may be responsible for the high level of occupational knee-morbidity found among carpet layers.     

Altered mRNA and Protein Expression of Monocarboxylate Transporter MCT1 in the Cerebral Cortex and Cerebellum of Prion Protein Knockout Mice

The effect of a cellular prion protein (PrP^c) deficiency on neuroenergetics was primarily analyzed via surveying the expression of genes specifically involved in lactate/pyruvate metabolism, such as monocarboxylate transporters (MCT1, MCT2, MCT4). The aim of the present study was to elucidate a potential involvement of PrP^c in the regulation of energy metabolism in different brain regions. By using quantitative real-time polymerase chain reaction (qRT-PCR), we observed a marked reduction in MCT1 mRNA expression in the cortex of symptomatic Zürich I Prnp^−/− mice, as compared to their wild-type (WT) counterparts. MCT1 downregulation in the cortex was accompanied with significantly decreased expression of the MCT1 functional interplayer, the Na⁺/K⁺ ATPase α2 subunit. Conversely, the MCT1 mRNA level was significantly raised in the cerebellum of Prnp^−/− vs. WT control group, without a substantial change in the Na⁺/K⁺ ATPase α2 subunit expression. To validate the observed mRNA findings, we confirmed the observed change in MCT1 mRNA expression level in the cortex at the protein level. MCT4, highly expressed in tissues that rely on glycolysis as an energy source, exhibited a significant reduction in the hippocampus of Prnp^−/− vs. WT mice. The present study demonstrates that a lack of PrP^c leads to altered MCT1 and MCT4 mRNA/protein expression in different brain regions of Prnp^−/− vs. WT mice. Our findings provide evidence that PrP^c might affect the monocarboxylate intercellular transport, which needs to be confirmed in further studies.     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.