Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish

The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular-cardiovascular disease states.
Glycolytic reprogramming through PCK2 regulates tumor initiation of prostate cancer cells

Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates. PCK2 knockdown resulted in low TIC numbers, increased cytosolic acetyl-CoA and cellular protein acetylation. Our data suggest PCK2 promotes tumor initiation by lowering acetyl-CoA level through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate tumors.
Verfahren zum automatisierten Auffinden von Zielpositionen, die von einem Fahrzeug in einer Umgebung anzufahren sind

Die vorliegende Erfindung betrifft ein Verfahren zum automatisierten Auffinden von Zielpositionen, die von einem Fahrzeug in einer Umgebung anzufahren sind, wobei das Fahrzeug eine bilderkennende Einrichtung aufweist sowie eine Einrichtung zum Speichern von erkannten Bildinformationen sowie eine Einrichtung zum Vergleich von aktuellen Bildinformationen mit gespeicherten Bildinformationen, wobei bei einer erkannten Zielposition mittels der bilderkennenden Einrichtung die Umgebung erfasst wird, wobei die erkannten Bildinformationen zu dieser Umgebung gespeichert werden, wobei beim kunftigen Aufsuchen von Zielpositionen die gespeicherten Bildinformationen mit aktuellen Bildinformationen verglichen werden, um mittels einer Korrelation zwischen den gespeicherten Bildinformationen und den aktuellen Bildinformationen in einer neuen Umgebung mogliche Zielpositionen zu erkennen.
High performance acetone sensor based on γ-Fe2O3/Al–ZnO nanocomposites

Ternary nanocomposites made of γ-iron oxide and aluminum-doped zinc oxide (γ-Fe2O3/Al–ZnO NCs), with different metal oxides ratio (0%–100%) were prepared through a solvothermal sol–gel process. The synthesized materials were characterized by x-ray diffraction, UV–vis spectroscopy, photoluminescence (PL), scanning electron microscope and BET analysis. Characterization results demonstrated that the ternary γ-Fe2O3/Al–ZnO NCs are mainly constituted by γ-Fe2O3 and Al–ZnO individual phases, while structural and physical properties like surface area, pore size, optical band gap, PL and electrical conductivity were deeply affected by the composition of nanocomposite. The synthesized γ-Fe2O3/Al–ZnO NCs were employed to prepare conductometric gas sensors, then their sensing performances toward acetone were also investigated. Results revealed enhanced sensing performance of nanocomposites than both pure γ-Fe2O3 and Al–ZnO phases. In particular, the γ-Fe2O3(33%)/Al–ZnO based gas sensor showed the best sensing properties, like a high response of Rair/Rgas = 29, a short response time of 3 s, in addition to an improved selectivity toward acetone versus ethanol at an operating temperature of 200 °C. Overall, ternary γ-Fe2O3/Al–ZnO NCs appear to be promising for the development of conductometric acetone sensors.
Illustrating and homology modeling the proteins of the Zika virus

The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening.
What is the appropriate communication style for family members confronting difficult surrogate decision-making in palliative care?: A randomized video vignette study in medical staff with working experiences of clinical oncology

Background The family members of terminally ill patients are often requested to make difficult surrogate decisions during palliative care. This study sought to clarify the appropriate communication style for physicians as perceived by family members confronting difficult surrogate decision-making. Methods This experimental psychological study used scripted videos. In the videos, the physician described treatment options including continuous deep sedation to the family members of patients with cancer and terminal delirium using an autonomous or paternalistic style. Medical professionals with clinical experience in oncology were randomly assigned to either group viewing the videos. The primary outcomes were physician compassion, decisional conflict and emotion scores. We also evaluated the communication style preference. Results In total, 251 participants completed this study. Although participants in both groups reported high physician compassion, participants in the autonomous style group reported lower compassion scores (reflecting higher physician compassion) (mean 15.0 vs. 17.3, P = 0.050), lower decisional conflicts scores (51.1 vs. 56.8, P = 0.002) and comparable emotions compared with those in the paternalistic style group. Seventy-six percent of participants preferred the autonomous style. Conclusions Regarding difficult surrogate decision-making, the autonomous style might be more appropriate than the paternalistic style. However, various factors, such as family members' communication style preferences, family members' values, physician-family relationships and ethnic cultures, should be considered.
Dressings used to prevent surgical site infection in the postoperative period of cardiac surgery: integrative review.

OBJECTIVE To identify and describe which dressings are recommended to prevent surgical site infection in hospitalized adult patients after cardiac surgeries. METHOD Integrative review carried out in the databases MEDLINE, LILACS, CINAHL, Web of Science, Cochrane and Scopus. Studies related to dressing in the postoperative period of cardiac surgery were selected. RESULTS Seven articles were included, with the following dressings: negative pressure wound therapy, silver nylon dressing, transdermal delivery of continuous oxygen and impermeable adhesive drape. The dressings that led to reduction of infection were negative pressure and silver nylon dressings. CONCLUSION It was not possible to identify which dressing is most recommended, however, some studies show that certain types of dressings were related to the reduction of infection. Clinical trials with a rigorous methodological design and representative samples able to minimize the risk of bias should be conducted to evaluate the effectiveness of dressings in the prevention of surgical site infection.
Through the mother’s voice: Exposure and intimacy in Lesley McIntyre’s photo project The Time of Her Life and Elisabeth Zahnd Legnazzi’s Chiara A Journey Into Light

When it comes to depicting ill or disabled children, the ethics of representation becomes increasingly complex. The perception of photographs as voyeuristic and objectifying is of particular concern here and resonates with widespread fear about the eroticisation, mistreatment and exploitation of children. Although these fears are reasonable, this view does not take into account the voice and agenda of the photographic subject, disregards the possibility of recognition and the participatory nature of photography. In this article, I focus on photography as a collaborative practice. I analyse two photographic projects by photographers/mothers that document their ill and dying daughters – Lesley McIntyre’s photographic essay The Time of Her Life (2004) and Elisabeth Zahnd Legnazzi’s Chiara A Journey Into Light (2009). Illness in these projects is not experienced in isolation. Instead, the photographs and accompanying texts provide a space to engage in a dialogue which is built on the interdependency of all the participants of the photographic act – the photographer, the subject of the photograph and the viewer. My aim is to question how these projects construct experiences and articulate private expressions of illness and how the photographs enhance and/or challenge the mother–daughter bond. Alan Radley’s critical analysis of representations of illness, Emmanuel Lévinas’s and Maurice Blanchot’s perspectives on ethical philosophy and visual social semiotics approach developed by Kress and Van Leeuwen provide a guiding framework for this study.
Differentiation of pluripotent stem cells into striatal projection neurons: a pure MSN fate may not be sufficient

Huntington’s disease (HD) is an autosomal dominant inherited disorder leading to the loss inter alia of DARPP-32 positive medium spiny projection neurons (“MSNs”) in the striatum. There is no known cure for HD but the relative specificity of cell loss early in the disease has made cell replacement by neural transplantation an attractive therapeutic possibility. Transplantation of human fetal striatal precursor cells has shown “proof-of-principle” in clinical trials; however, the practical and ethical difficulties associated with sourcing fetal tissues have stimulated the need to identify alternative source(s) of donor cells that are more readily available and more suitable for standardization. We now have available the first generation of protocols to generate DARPP-32 positive MSN-like neurons from pluripotent stem cells and these have been successfully grafted into animal models of HD. However, whether these grafts can provide stable functional recovery to the level that can regularly be achieved with primary fetal striatal grafts remains to be demonstrated. Of particular concern, primary fetal striatal grafts are not homogenous; they contain not only the MSN subpopulation of striatal projection neurons but also include all the different cell types that make up the mature striatum, such as the multiple populations of striatal interneurons and striatal glia, and which certainly contribute to normal striatal function. By contrast, present protocols for pluripotent stem cell differentiation are almost entirely targeted at specifying just neurons of an MSN lineage. So far, evidence for the functionality and integration of stem-cell derived grafts is correspondingly limited. Indeed, consideration of the features of full striatal reconstruction that is achieved with primary fetal striatal grafts suggests that optimal success of the next generations of stem cell-derived replacement therapy in HD will require that graft protocols be developed to allow inclusion of multiple striatal cell types, such as interneurons and/or glia. Almost certainly, therefore, more sophisticated differentiation protocols will be necessary, over and above replacement of a specific population of MSNs. A rational solution to this technical challenge requires that we re-address the underlying question—what constitutes a functional striatal graft?
Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis

A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.
Spatial dynamics of industrial districts in knowledge cities: A case study of Hsinchu, Taiwan

Driven by globalization and international competition, the development of clusters of knowledge-based corporations has become an important factor in increasing the competitiveness of cities. Whereas previous studies have tended to focus on the characteristics of local clusters and the causes of their success, empirical studies of the long-term development of local knowledge-based industries are few. Accordingly, this investigation takes the Hsinchu region as its subject, and quantitatively analyzes the correlation between the spatial dynamics of knowledge in major industries and innovation based on empirical data. First, the annual Taiwan Industry, Commerce and Service Census is utilized to identify major industries in the Hsinchu region. Significant differences in the major industries in the Hsinchu are identified from variations in their location quotients. Second, the dynamic evolution of major industries in the Hsinchu district is analyzed by curvilinear regression analysis. The results reveal that the clustering of chemical materials and chemical products manufacturing, non-metallic mineral product manufacturing, and support service industries, has been falling over the last 15 years, while industries with close ties to HSIP, including electronic components manufacturing, computer and electronic product manufacturing, and the manufacturing of other optical products, have remained stable. Finally, simple logistic regression is used to elucidate the correlation between the local industries and innovation. Two variables, product innovation and percentage of turnover invested in product innovation, have both increased significantly in electronic component manufacturing, computer and electronic product manufacturing, and optical product manufacturing industries. This finding shows that steadily developing industries in the Hsinchu region have continued to strengthen their new knowledge of product development and innovation. An overview of innovative activities of firms also revealed that their knowledge patterns have been changing from patterns of internal dependency to a locality-based, broader networking and agglomeration pattern.
Effect of S-equol and Soy Isoflavones on Heart and Brain

Background: Observational studies in Asia show that dietary intake of soy isoflavones had a significant inverse association with coronary heart disease (CHD). A recent randomized controlled trial (RCT) of soy isoflavones on atherosclerosis in the US, however, failed to show their benefit. The discrepancy may be due to the much lower prevalence of S-equol producers in Westerners: Only 20-30% of Westerners produce S-equol in contrast to 50-70% in Asians. S-equol is a metabolite of dietary soy isoflavone daidzein by gut microbiome and possesses the most anti-atherogenic properties among all isoflavones. Several short-duration RCTs documented that soy isoflavones improves arterial stiffness. Accumulating evidence shows that both atherosclerosis and arterial stiffness are positively associated with cognitive decline/dementia. Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia. Methods/Results: This narrative review of clinical and epidemiological studies provides an overview of the health benefits of soy isoflavones and introduces S-equol. Second, we review recent evidence on the association of soy isoflavones and S-equol with CHD, atherosclerosis, and arterial stiffness as well as the association of atherosclerosis and arterial stiffness with cognitive decline/dementia. Third, we highlight recent studies that report the association of soy isoflavones and S-equol with cognitive decline/dementia. Lastly, we discuss the future directions of clinical and epidemiological research on the relationship of S-equol and CHD and dementia. Conclusions: Evidence from observational studies and short-term RCTs suggests that S-equol is anti-atherogenic and improves arterial stiffness and may prevent CHD and cognitive impairment/dementia. Well-designed long-term (≥ 2years) RCTs should be pursued.
A method to estimate synaptic conductances from membrane potential fluctuations.

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential (V(m)) fluctuations, commonly called "synaptic noise. " This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold V(m) distribution at steady state in conductance-based models. Fitting this analytic expression to V(m) distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.
Hereditary spastic paraplegia: gain‐of‐function mechanisms revealed by new transgenic mouse

Abstract Mutations of the SPAST gene, which encodes the microtubule‐severing protein spastin, are the most common cause of hereditary spastic paraplegia (HSP). Haploinsufficiency is the prevalent opinion as to the mechanism of the disease, but gain‐of‐function toxicity of the mutant proteins is another possibility. Here, we report a new transgenic mouse (termed SPASTC448Y mouse) that is not haploinsufficient but expresses human spastin bearing the HSP pathogenic C448Y mutation. Expression of the mutant spastin was documented from fetus to adult, but gait defects reminiscent of HSP (not observed in spastin knockout mice) were adult onset, as is typical of human patients. Results of histological and tracer studies on the mouse are consistent with progressive dying back of corticospinal axons, which is characteristic of the disease. The C448Y‐mutated spastin alters microtubule stability in a manner that is opposite to the expectations of haploinsufficiency. Neurons cultured from the mouse display deficits in organelle transport typical of axonal degenerative diseases, and these deficits were worsened by depletion of endogenous mouse spastin. These results on the SPASTC448Y mouse are consistent with a gain‐of‐function mechanism underlying HSP, with spastin haploinsufficiency exacerbating the toxicity of the mutant spastin proteins. These findings reveal the need for a different therapeutic approach than indicated by haploinsufficiency alone.