Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical stress induces profound remodelling of keratin filaments and cell junctions in epidermolysis bullosa simplex keratinocytes

The outer epidermal layer of the skin is an epithelium with remarkable protective barrier functions, which is subject to pronounced physical stress in its day-to-day function. A major candidate component for absorbing this stress is the K5/K14 keratin intermediate filament network. To investigate the part played by keratins in stress resilience, keratinocyte cell lines were subjected to mechanical stress. Repeated stretch and relaxation cycles over increasing time produced reproducible changes in the configuration of the keratin network. When wild-type cells were compared with cells carrying a keratin mutation associated with severe epidermolysis bullosa simplex-type skin fragility, the mutant keratin filaments were unable to withstand the mechanical stress and progressively fragmented yielding aggregates and novel ring structures. The cell junctions into which the keratin filaments are normally anchored also progressively disassembled, with all components tested of the cytoplasmic plaques becoming relocated away from the membrane and onto the keratin rings, while integral membrane receptors integrins and cadherins remained at the plasma membrane. The results suggest that maintenance of desmosomes and hemidesmosomes may require some tension, normally mediated by keratin attachments.
The resilience of Australian wind energy to climate change

The Paris Agreement limits global average temperature rise to 2 °C and commits to pursuing efforts in limiting warming to 1.5 °C above pre-industrial levels. This will require rapid reductions in the emissions of greenhouse gases and the eventual decarbonisation of the global economy. Wind energy is an established technology to help achieve emissions reductions, with a cumulative global installed capacity of ~486 GW (2016). Focusing on Australia, we assess the future economic viability of wind energy using a 12-member ensemble of high-resolution regional climate simulations forced by Coupled Model Intercomparison Project (CMIP) output. We examine both near future (around 2030) and far future (around 2070) changes. Extractable wind power changes vary across the continent, though the most spatially coherent change is a small but significant decrease across southern regions. The cost of future wind energy generation, measured via the Levelised Cost of Energy (LCOE), increases negligibly in the future in regions with significant existing installed capacity. Technological developments in wind energy generation more than compensate for projected small reductions in wind, decreasing the LCOE by around 30%. These developments ensure viability for existing wind farms, and enhance the economic viability of proposed wind farms in Western Australian and Tasmania. Wind energy is therefore a resilient source of electricity over most of Australia and technological innovation entering the market will open new regions for energy production in the future.
The Value of a Statistical Life in a Dictatorship: Evidence from Stalin

We examine the value of a statistical life (VSL) in interwar Soviet Union. Our approach requires addressing the preferences of Stalin. We model these on the basis of the policy of statistical repression, which was an integral part of the Great Terror. We use regional variation in the victims generated by this policy to structurally estimate the value that Stalin would have been willing to accept for a reduction in citizens’ fatality risk. Our estimate of this value is $43,000, roughly 6% of the VSL estimate in the US in 1940 and 29% of the VSL estimate in modern India.
Efficient control system development using Model Based Development

Currently, almost all automotive and supplier companies are trying to expand model based development (MBD) for control system development. To shorten the development period, concurrent development of hardware and software is effective. Moreover, the control logic complexity is becoming higher in accordance with the implementation of new sensors, actuators, improved control system performance, and increased the interface with another ECU. One significant process of the MBD is the ECU verification with the plant model installed in HILS. We describe some key points for HILS in hybrid system development.
Nephrotoxic potential of Bence Jones proteins.

BACKGROUND The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. METHODS Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. RESULTS Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 mumol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 mumol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. CONCLUSIONS Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain-associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains.
The Tricuspid Valve Annulus: Study of Size and Motion in Normal Subjects and in Patients with Tricuspid Regurgitation

The tricuspid valve leaflets and their annular attachments were recorded by two-dimensional echocardiography from a view of the right ventricular inflow tract obtained by placing the transducer at an intermediate position between the left ventricular apex and the left lower sternal border. The transducer was rotated, and recordings were made at 300 rotational intervals around the circumference of the tricuspid valve annulus. The cyclical pattern of variations in tricuspid annular size was studied with 12 measurements made during the cardiac cycle in five normal subjects. Annular areas and circumferences were measured. The overall motion pattern was-similar to that reported in normal mitral valve annular study. Subsequently, in 16 normal subjects and 18 patients with tricuspid regurgitation, the maximum and minimum tricuspid annular sizes and their percent reduction were measured. The mean maximum annular circumference and area were 11.9 ± 0.9 cm (mean ± SD) and 11.3 ± 1.8 cm2 in normal subjects. They were significantly greater in tricuspid regurgitation (14.0 ± 0.7 cm and 15.8 ± 1.8 cm2, respectively). The mean minimum annular sizes were much larger in tricuspid regurgitation (12.5 ± 0.6 cm and 13.0 ± 1.4 cm2) than in normal subjects (9.6 ± 0.9 cm, 7.6 ± 1.4 cm2). Thus, the percent reduction of annular circumference and area were significantly decreased in tricuspid regurgitation. For anatomic correlations, measurements of the tricuspid annular circumference were made at autopsy in 18 hearts without underlying valvular disease. The annular circumference was measured in the fresh and fixed states. The measurement in the fresh state was 13.5 ± 0.8 cm and in the fixed state was 12.0 ± 0.8 cm. The values measured in the fixed hearts were more similar to measurements obtained by echocardiography in a group of normal subjects.Thus, tricuspid annular reconstruction by the new two-dimensional echocardiographic method provides additional information about normal and abnormal size and function of the tricuspid valve annulus.
Utilizing management accounting information for decision-making

Purpose To be utilized effectively in decision-making processes, management accounting (MA) information should fit the business context and at the same time reflect the roles, responsibilities and values of the actors taking part in the decision-making. This study aims to investigate the limitations for MA information utilization in decision-making. In particular, this study explores limitations stemming from the decision-making process structure and the involvement of several managerial actors. Design/methodology/approach An exploratory case study of an energy company and its customer company illustrates the current challenges in providing and integrating MA information into decision-making. The analysis is focused on the analytical and actor-based features of the decision-making and thus the limitations for MA information utilization. As a part of the broader research process, the researchers facilitated a meeting in the customer company, where the actors relevant to investment decisions discussed the current limitations in utilizing MA information. Findings Analytical and actor-based features may take different forms in the decision-making. Some relevant MA information may not be included in an organization’s decision-making process structure that allows merely conventional, yet analytical, decision alternatives. At the same time, certain actors’ viewpoints (such as sustainability metrics) can be excluded from the process without considering the logic behind the exclusion. This case study identifies the following limitations, largely related to insufficient actor-based features in the decision-making: managers may lack expertise in the use of MA tools, managerial interaction may lack reflection on taken-for-granted assumptions, different managers may appreciate different scope, content and timing of MA information and the process structure can ignore the required managerial viewpoints. Research limitations/implications This study demonstrates that both the decision-making process structure and the needs of the several actors involved may lead to limitations for MA information utilization. Although many limitations stemmed from the insufficient actor-based orientation in the case study, introducing new MA analyses and extending the validity of analytical approaches may also help overcome some of the limitations. Further research should address possibilities to integrate different actors’ viewpoints with MA information already in the decision-making process structure, find ways to introduce MA information on unconventional decision alternatives and enable reflection among and about relevant actors with respect to decision-making. These means could lead to more effective utilization of MA information for decision-making and, consequently, economically viable decisions. Originality/value This study addresses the limitations in MA information utilization by combining the viewpoints of analytical decision-making processes and reflective actors, and thus unveils possibilities for enhancing MA practice.
Fluorescence and kinetic analysis of the SpoIIAB phosphorylation reaction, a key regulator of sporulation in Bacillus subtilis.

Sporulation in Bacillus subtilis provides a valuable model system for studying differential gene expression. The anti-sigma factor SpoIIAB is a bifunctional protein, responsible for regulating the activity of the first sporulation-specific sigma factor, sigma(F). SpoIIAB can either bind to (and thus inhibit) sigma(F) or phosphorylate the anti-anti-sigma factor SpoIIAA. The phosphorylation reaction follows an unusual time course in which a pre-steady-state phase is succeeded by a slower steady-state phase. Previous experiments have shown that in the steady-state phase SpoIIAB is unable to inhibit sigma(F). A fluorescent derivative of SpoIIAB (AB-F97W) was made that was indistinguishable from the wild type in its interactions with SpoIIAA and sigma(F). AB-F97W exhibited distinctive changes in its fluorescence intensity when bound to ATP, ADP, or SpoIIAA. By following changes in the fluorescence properties of AB-F97W during the phosphorylation reaction, we confirmed a previous hypothesis that during the steady-state phase the predominant species are SpoIIAA.SpoIIAB. ADP complexes. The formation of these complexes is responsible for the slowing of the reaction, an important feature during sporulation since it reduces the loss of ATP in the nutrient-deprived cell. We also show that, to form a complex with SpoIIAA and ADP during the reaction, SpoIIAB must undergo a change in state which increases its affinity for ADP, and that this change in state is stimulated by its interaction with SpoIIAA. We derive a model of the reaction using previously determined kinetic and binding constants, and relate these findings to the known structure of SpoIIAB.
Correlates of chemosensory malingering

Smell and taste tests are commonly employed to quantify chemosensory sequelae of head trauma, toxic exposures, and iatrogenesis. Malingering on forced‐choice chemosensory tests can be detected by improbable responding. This study determined whether chemosensory test malingerers differ from nonmalingerers in terms of age, sex, education, and a range of self‐reported behaviors and symptoms, potentially providing information of value for malingering detection.
Efficacy of papillary muscle approximation in preventing functional mitral regurgitation recurrence in high-risk patients with ischaemic cardiomyopathy and mitral regurgitation.

BACKGROUND Dilated cardiomyopathy (DCM) is often complicated by the appearance of functional mitral regurgitation (FMR). Although mitral ring annuloplasty (MAP) is the most widely used surgical procedure for the surgical treatment of FMR, there are still reports of patients who suffer recurrent FMR at later follow-ups. We sought to investigate the efficacy of papillary muscle approximation (PMA) combined with MAP in preventing the recurrence of FMR in high-risk patients. METHODS One hundred patients with ischaemic (74%) or non-ischaemic (26%) DCM along with severe (4+/4+) or moderately severe (3+/4+) FMR were enrolled in this prospective, cross-sectional study. According to the interpapillary muscle distance (iPMD) and coaptation depth (CD), the patients were risk stratified as low (iPMD + CD 30 mm, n= 69) and high-risk (iPMD + CD > 30 mm, n= 31) groups. The low-risk patients underwent only MAP, whereas the high-risk patients underwent MAP plus PMA. RESULTS After a mean +/- SD follow-up of 40.8 +/- 12.5 months, recurrence of 3+ to 4+ MR was observed in 8 (8.7%) and 7 (11.1%) patients in the annuloplasty group (MAP-only) and one (3.4%) patient in the combination group (MAP plus PMA) (P= 0.428). At the final follow-up, the New York Heart Association (NYHA) function class was 1.57 +/- 0.62 in the annuloplasty group and 1.45 +/- 0.57 in the combination group; there was no significant difference in NYHA function class between the first and final follow-ups (P> 0.05). CONCLUSION iPMD is a valuable index in the riskstratification of the recurrence of post-MAP MR in patients with DCM complicated by FMR.The patients treated with MAP plus PMA had more favourable outcomes and lower recurrence rates than those treated via the traditional route of MAP only.
Three-Dimensional Culture of Human Periodontal Ligament Cells on Highly Porous Polyglycolic Acid Scaffolds in vitro

Periodontal tissue engineering represents a possible approach to regenerate the human periodontal ligament (PDL) around dental implants. The aim of this study was to observe the morphological and biological property of the human periodontal ligament cells that were three-dimensional (3D) cultured onto PGA scaffolds in vitro. The human periodontal ligament cells were seeded and cultured onto PGA 3D scaffolds, and then the cellular morphology and structure, adhesion and biocompatibility with scaffolds were evaluated by light microscope and scanning electronic microscope, and the cellular type I collagen synthesis was observed by method of immunohistochemical staining with anti-type I collagen antibody. The results indicated that the human periodontal ligament cells adhere to scaffolds well and exhibit the excellent matrix secretion ability under light microscope and scanning electronic microscope, type I collagen was expressed positively in cell-scaffolds complex by immunohistochemical staining. These results suggested that delivery of PDL cells via non-woven PGA mesh may serve as a viable approach for promoting periodontal tissue regeneration and provides a possibility of PDL regeneration on dental implants
QTLNetworkR: an interactive R package for QTL visualization

QTLNetworkR is an R package that aims to provide a user-friendly and platform-independent tool to visualize quantitative trait loci (QTL) mapping results. The graphical functions of the QTLNetworkR are based upon lattice and grid packages, and the graphical user interface (GUI) of the QTLNetworkR is built upon RGtk2 and gWidgetsRGtk2 packages. Six functions are designed to help visualize marker interval, putative QTL, QTL-by-environment interactions, marker interval interactions, epistasis, and the predicted genetic architecture of complex traits. It is especially helpful in profiling results for multiple traits at multiple environments. The current version of QTLNetworkR is able to accept QTL mapping results from QTLNetwork, and it is ready for possible extensions to import results from some other QTL mapping software packages. In addition, we presented a QTL mapping result in rice (Oryza sativa) as an example to describe the features of QTLNetworkR.
Ecosystem services bundles: challenges and opportunities for implementation and further research

Background: the concept of ‘ecosystem services bundles’, i.e. ecosystem services that repeatedly appear together across space and/or time, has been developed and refined as part of an integrated approach to assess interactions between ecosystem services. Nevertheless, published evidence of actual use of bundles in decision-making is lacking. In the light of this gap, a review of what bundle approaches have shown and what they can bring to decision-making is timely. Method: we conducted two separate systematic reviews. The first one addressed emerging issues within what we identify as the diverse utilisation and definition of the concept of ‘bundle’ in the literature. The second one focused on papers dealing with bundles as sets of consistently associated services. Review Synthesis: the review first highlights that the confusion surrounding the term ‘bundle’ in ecosystem services literature threatens to weaken the potential for analysis of bundles to inform decision-making. Then, thanks to the review of peer-reviewed papers that detect bundles as sets of consistently associated services, we analyse the diversity of methodological choices and we detail the interactions observed between different ecosystem services across the literature. We also show that landscape features, socio-economic conditions and institutional factors are all potential drivers for the occurrence of specific bundles in a landscape. Discussion: overall, it appears that the analysis of bundles provides an opportunity to enhance policy effectiveness. Nevertheless, the methodological challenges linked to the identification and interpretation of bundles call for careful and reflective study designs. We anticipate that this review will lead to a better understanding by scientists and practitioners of the potential for bundle studies to inform decision-making.
Selective Transduction of Mature DC in Human Skin and Lymph Nodes by CD80/CD86-targeted Fiber-modified Adenovirus-5/3

In vivo targeting of dendritic cells (DC) represents an attractive alternative to currently apply ex vivo DC-based genetic tumor vaccination protocols. Finding the optimal vector for in vivo targeting of DC is important for such strategies. We, therefore, tested a panel of subgroup C/B chimeric and fiber-modified adenoviruses (Ads) for their relative capacity to transduce human DC. We made use of in vitro generated Langerhans cells, and of ex vivo human skin and melanoma-draining lymph node derived DC. Of the tested viruses the C/B-chimeric adenovirus serotype 5 (Ad5)/3 virus most efficiently transduced in vitro generated Langerhans cells. In addition, Ad5/3 preferentially targeted mature myeloid DC from human skin and draining lymph node and transduced them at significantly higher frequencies than Ad5. In addition, Ad5/3 was more specific for mature human skin-derived CD1a+ CD83+ DC than the previously reported DC-transducing C/B-chimeric vector Ad5/35, infecting less bystander cells. It was previously reported that Ad5/3 transduced human monocyte-derived DC by binding to the B7 molecules CD80 and CD86. High-efficiency transduction of mature skin-derived DC was similarly shown to be mediated through binding to CD80/CD86 and not to interfere with subsequent T-cell priming. We conclude that Ad5/3, in combination with DC-activating adjuvants, represents a promising therapeutic tool for the in vivo transduction of mature DC, and may be less likely to induce unwanted side effects such as immune tolerance through the infection of nonprofessional antigen-presenting cells.
Synchronous replication of poliovirus RNA: initiation of negative-strand RNA synthesis requires the guanidine-inhibited activity of protein 2C

We report that protein 2C, the putative nucleoside triphosphatase/helicase protein of poliovirus, is required for the initiation of negative-strand RNA synthesis. Preinitiation RNA replication complexes formed upon the translation of poliovirion RNA in HeLa S10 extracts containing 2 mM guanidine HCI, a reversible inhibitor of viral protein 2C. Upon incubation in reactions lacking guanidine, preinitiation RNA replication complexes synchronously initiated and elongated negative-strand RNA molecules, followed by the synchronous initiation and elongation of positive-strand RNA molecules. The immediate and exclusive synthesis of negative-strand RNA upon the removal of guanidine demonstrates that guanidine specifically blocks the initiation of negative-strand RNA synthesis. Readdition of guanidine HCl to reactions synchronously elongating nascent negative-strand RNA molecules did not prevent their continued elongation and completion. In fact, readdition of guanidine HCl to reactions containing preinitiation complexes elongating nascent negative-strand RNA molecules had no effect on subsequent positive-strand RNA synthesis initiation or elongation. Thus, the guanidine-inhibited function of viral protein 2C was not required for the elongation of negative-strand RNA molecules, the initiation of positive-strand RNA molecules, or the elongation of positive-strand RNA molecules. The guanidine-inhibited function of viral protein 2C is required only immediately before or during the initiation of negative-strand RNA synthesis. We suggest that guanidine may block an irreversible structural maturation of protein 2C and/or RNA replication complexes necessary for the initiation of RNA replication.