Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of p16INK4a in Urothelial Carcinoma In Situ Is a Marker for MAPK-Mediated Epithelial-Mesenchymal Transition but Is Not Related to Human Papillomavirus Infection

Background The role of human papillomavirus (HPV) in bladder carcinogenesis remains controversial. Overexpression of p16INK4a, a surrogate marker for infection with oncogenic HPV in other tumours, has been described for urothelial carcinoma in situ (UCIS). Our goal was therefore to evaluate whether overexpression of p16INK4a is associated with HPV infection and to identify mechanisms of p16INK4a upregulation in UCIS. Materials and Methods In 60 tissue specimens from a total of 45 patients (UCIS and controls), we performed p16INK4a immunohistochemistry followed by detection and subclassification of HPV DNA. In a subset of samples, we tested for gene amplification of p16INK4a applying fluorescence in situ hybridization (FISH). RAS/MAPK signalling and epithelial-mesenchymal transition (EMT) was assessed using immunohistochemistry. Finally, we transfected urothelial carcinoma cells with KRAS and examined the expression of p16INK4a as well as markers of EMT. Results We found overexpression of p16INK4a in 92.6% of UCIS and in all cervical intraepithelial neoplasia (CIN) controls. In contrast, we detected high-risk HPV DNA in 80% of CIN, but none in UCIS. There was no gene amplification of p16INK4a. High levels of phosphorylated kinases and urokinase plasminogen activator (uPA) and loss of membraneous E-cadherin were detected in UCIS. KRAS transfection of urothelial carcinoma cells led to upregulation of p16INK4a and uPA accompanied by loss of E-cadherin that could be inhibited by application of the kinase-inhibitor Sorafenib. Conclusions Our results show that overexpression of p16INK4a in UCIS is neither associated with HPV infection nor p16INK4a gene amplification but is a consequence of enhanced RAS/MAPK signalling that promotes EMT, possibly due to Sorafenib-sensitive paracrine secretion of the EMT activator uPA. These findings might open a novel therapeutic option for localized but aggressive urothelial cancer.
Activation of σ20-dependent recombination and horizontal gene transfer in Mycoplasma genitalium

Abstract In the human pathogen Mycoplasma genitalium, homologous recombination is under the control of σ20, an alternative sigma factor that boosts the generation of genetic and antigenic diversity in the population. Under laboratory growth conditions, σ20 activation is rare and the factors governing its intermittent activity are unknown. Two σ20-regulated genes, rrlA and rrlB, showed to be important for recombination of homologous DNA sequences in this bacterium. Herein, we demonstrate that rrlA and rrlB code for two small proteins that participate in a feed-forward loop essential for σ20 function. In addition, we identify novel genes regulated by σ20 and show that several non-coding regions, which function as a reservoir for the generation of antigenic diversity, are also activated by this alternative sigma factor. Finally, we reveal that M. genitalium cells can transfer DNA horizontally by a novel mechanism that requires RecA and is facilitated by σ20 over-expression. This DNA transfer system is arguably fundamental for persistence of M. genitalium within the host since it could facilitate a rapid dissemination of successful antigenic variants within the population. Overall, these findings impose a novel conception of genome evolution, genetic variation and survival of M. genitalium within the host.
Insulin degludec's ultra‐long pharmacokinetic properties observed in adults are retained in children and adolescents with type 1 diabetes

Insulin degludec (IDeg) is a basal insulin with an ultra‐long pharmacokinetic profile in adults that at steady‐state produces remarkably flat and stable insulin levels; however, no studies have yet reported on the pharmacokinetic properties of IDeg in subjects younger than 18 years of age. This was a single‐centre, randomised, single‐dose, double‐blind, two‐period crossover trial conducted in children (6–11 years), adolescents (12–17 years), and adults (18–65 years) with type 1 diabetes. Subjects received a single subcutaneous dose of 0.4 U/kg IDeg or insulin glargine (IGlar), respectively, on two separate dosing visits, with pharmacokinetic blood sampling up to 72‐h postdose. A total of 37 subjects (12 children, 13 adolescents, and 12 adults) completed the trial. Total exposure of IDeg after a single dose (AUCIDeg,0‐∞,SD) was higher in children compared to adults [estimated ratio children/adults 1.48 (95% confidence interval, CI: 0.98; 2.24)] and in adolescents compared to adults [estimated ratio adolescents/adults 1.33 (95% CI: 1.08; 1.64)]; however, the difference was only statistically significant for the latter comparison. No statistically significant difference in maximum concentration of IDeg (Cmax,IDeg,SD) was observed. Estimated ratios for Cmax,IDeg,SD were (children/adults) 1.20 (95% CI: 0.90; 1.60) and (adolescents/adults) 1.23 (95% CI: 1.00; 1.51). Simulated mean steady state pharmacokinetic profiles supported a flat and stable IDeg exposure across a 24‐h dosing interval. IDeg was detectable in serum for at least 72 h (end of blood sampling period) in all subjects following single dose. In conclusion, the ultra‐long pharmacokinetic properties of IDeg observed in adults are preserved in children and adolescents with type 1 diabetes.
Lignosulfonate To Enhance Enzymatic Saccharification of Lignocelluloses: Role of Molecular Weight and Substrate Lignin

This study conducted an investigation of the effect of lignosulfonate (LS) on enzymatic saccharification of lignocelluloses. Two commercial LSs and one laboratory sulfonated kraft lignin were applied to Whatman paper, dilute acid and SPORL (sulfite pretreatment to overcome recalcitrance of lignocelluloses) pretreated aspen, and kraft alkaline and SPORL pretreated lodgepole pine. All three lignin samples inhibited cellulose saccharification of Whatman paper, but enhanced the saccharification of the four lignocellulosic substrates. The level of enhancement was related to the molecular weight and degree of sulfonation of the lignin as well as the substrate lignin structure. When different molecular weight (MW) fractions of one commercial LS (SXP), generated from sulfite pulping of hardwood, were applied to the Whatman paper, the large MW fraction (SXP1) with the lowest degree of sulfonation inhibited cellulose saccharification while the intermediate (SXP2) and smallest (SXP3) MW fractions enhanced saccharifi.
Retro-inverso follicle-stimulating hormone peptide-mediated polyethylenimine complexes for targeted ovarian cancer gene therapy

Abstract Background: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer. Methods: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation. Results: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively. Conclusions: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy.
Comparison of Two School-Based Smoking Prevention Programs among South African High School Students : Results of a Randomized Trial

Thirty-six public schools from two South African provinces, KwaZulu-Natal and the Western Cape, were stratified by socioeconomic status and randomized to one of three groups. Group 1 (comparison) schools (n = 12) received usual tobacco use education. Group 2 schools (n = 12) received a harm minimization curriculum in grades 8 and 9. Group 3 schools (n = 12) received a life skills training curriculum in grades 8 and 9. The primary outcome was past month use of cigarettes based on a self-reported questionnaire.
Effect of micro-roughening of poly(ether ether ketone) on bone marrow derived stem cell and macrophage responses, and osseointegration

Abstract Poly(ether ether ketone) (PEEK) has emerged as a candidate to replace metal implants because of its satisfactory mechanical properties, radiolucency, and lack of metal allergy. However, PEEK lacks osseointegration ability limiting its clinical applications. To overcome this problem, we prepared PEEK with a micro-rough surface using the sandblast method to modulate its osseointegration property; the sandblast method is simple, cost-effective, and is already applied to clinical metal implants. The surface roughness of the sandblasted PEEK was about 2.3 μm, whereas that of mirror-polished PEEK was 0.06 μm. Rat bone marrow-derived mesenchymal stem cells (RMSCs) showed higher proliferation, osteocalcin (OC) expression and bone-like nodule formation on micro-roughened PEEK compared with those cultured on mirror-polished PEEK, suggesting that micro-roughening facilitated RMSCs proliferation and differentiation. The micro-roughened surface slightly mitigated secretion of inflammatory C-C motif chemokine 2 (CCL-2) from lipopolysaccharide (LPS)-stimulated macrophages, but not of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). Finally, to compare osseointegration, specimens were implanted in rat femur bone marrow cavities, and then the pull-out force was measured. The pull-out force of micro-roughened PEEK was about four times higher than that of the mirror-polished PEEK. These results showed that micro-roughening of PEEK using the sandblast method was able to improve osseointegration, partly through elevating proliferation and differentiation of RMSCs.
A Theory of Mergers and Acquisitions : Synergy , Private Benefits , or Hubris Hypothesis

In this paper, we apply the perfect Bayesian equilibrium concept to analyze the equilibrium for takeover game, and then using the necessary conditions of the equilibrium to explain the reason why takeovers are motivated. Our theoretical results show that synergy, private benefits and hubris hypotheses may all explain why companies engage in mergers and acquisitions; the critical point between the motives is the management of the acquiring firm how to confirm the movement and strategies of the target firm. When the management of the acquiring firm indefinitely knows the target firm whether resists or co-operates, the hubris and synergy hypotheses both are supported. When the management of the acquiring firm definitely believes the target firm will resist, then the private benefits hypothesis is supported. The findings indicate that, in certain circumstances, the more overconfident the management of the acquiring firm and the greater private benefits will be, the more likely the merger and acquisition will be motivated.
Application of In Situ Techniques for the Characterization of NiFe-Based Oxygen Evolution Reaction (OER) Electrocatalysts.

Developing high-efficiency and affordable electrocatalysts for the sluggish oxygen evolution reaction (OER) remains a crucial bottleneck on the way to the practical applications of rechargeable energy storage technologies and water splitting for producing clean fuel (H2 ). In recent years, NiFe-based materials have proven to be excellent electrocatalysts for OER. Understanding the characteristics that affect OER activity and determining the OER mechanism are of vital importance for the development of OER electrocatalysts. Therefore, in situ characterization techniques performed under OER conditions are urgently needed to monitor the key intermediates together with identifying the OER active centers and phases. In this Minireview, recent advances regarding in situ techniques for the characterization of NiFe-based electrocatalysts are thoroughly summarized, including Raman spectroscopy, X-ray absorption spectroscopy, ambient pressure X-ray photoelectron spectroscopy, Mössbauer spectroscopy, Ultraviolet-visible spectroscopy, differential electrochemical mass spectrometry, and surface interrogation scanning electrochemical microscopy. The results from these in situ measurements not only reveal the structural transformation and the progressive oxidation of the catalytic species under OER conditions, but also disclose the crucial role of Ni and Fe during the OER. Finally, the need for developing new in situ techniques and theoretical investigations is discussed to better understand the OER mechanism and design promising OER electrocatalysts.
Medicinal Properties of Tinospora Cordifolia (Guduchi)

Tinospora cordifolia is one of the most important medicinal plant commonly known as Giloy belonging to menispermaceae family is a deciduous climbing shrub described known for its immense application in the treatment of various diseases such as jaundice, fever, diabetes, and skin diseases etc.The chemical constituents of this shrub belong to different classes such as alkaloid, lactones, steroids, phenolics, aliphatic compound, glycosides and polyscharide compounds having medical importance.
Collaborative object picking and delivery with a team of micro aerial vehicles at MBZIRC

Picking and transporting objects in an outdoor environment with multiple lightweight MAVs is a demanding task. The main challenges are sudden changes of flight dynamics due to altered center of mass and weight, varying lighting conditions for visual perception, and coordination of the MAVs over unreliable wireless connections. At the Mohamed Bin Zayed International Robotics Challenge (MBZIRC) teams competed in a Treasure Hunt where three MAVs had to collaboratively pick colored disks and drop them into a designated box. Only little preparation and test time on- site required robust algorithms and easily maintainable systems to successfully achieve the challenge objectives. We describe our multi-robot system employed at MBZIRC, including a lightweight gripper, a vision system robust against illumination and color changes, and a control architecture allowing to operate multiple robots safely. With our system, we—as part of the larger team NimbRo of ground and flying robots—won the Grand Challenge and achieved a third place in the Treasure Hunt.
Estimation of mental workload using saccadic eye movements in a free-viewing task

This study proposes a new method to automatically estimate a person's mental workload (MWL) using a specific type of eye movements called saccadic intrusions (SI). Previously, the most accurate existing method to estimate MWL was the pupil diameter measure [1]. However, pupil diameter is not practical in a vehicle driving environment because it is overly sensitive to brightness changes. A new method should be independent from environment brightness changes, robust in most driving environments, and accurately reflect MWL. This study used SI as an indicator of MWL because eye movements, including SI, are independent from brightness changes. SI are a specific type of eye-gaze deviations. SI are known to be closely related to cognitive activities [2], [3]. This means that SI may be also closely related to MWL. Eye movements were recorded using a non-intrusive eye tracking camera, located 550 mm away from a participant. Participants were instructed to move their eye gaze to examine a highway driving scenery picture. In the data set of the recorded eye movements, our new algorithm detected SI and quantified SI behavior into a SI measure. Participants were also engaged in a secondary N-back task. The N-back task is a popular task used in cognitive sciences to systematically control a MWL level of participants. In our results, all 14 participants exhibited more SI eye movements when their MWL level was high compared to when their MWL level was low. Moreover, our results showed that the SI measure was a more accurate measure of MWL than the pupil diameter measure. This finding indicates that MWL of the person can be estimated by observation of SI eye movements. This new method has a wide range of applications. One of them is to predict a person's MWL, thus predicting when a person is capable of driving a vehicle in a safe or dangerous manner.
Sub-uJ deep neural networks for embedded applications

To intelligently process sensor data on internet of things (IoT) devices, we require powerful classifiers that can operate at sub-uJ energy levels. Previous work has focused on spiking neural network (SNN) algorithms, which are well suited to VLSI implementation due to the single-bit connections between neurons in the network. In contrast, deep neural networks (DNNs) are not as well suited to hardware implementation, because the compute and storage demands are high. In this paper, we demonstrate that there are a variety of optimizations that can be applied to DNNs to reduce the energy consumption such that they outperform SNNs in terms of energy and accuracy. Six optimizations are surveyed and applied to a SIMD accelerator architecture. The accelerator is implemented in a 28nm SoC test chip. Measurement results demonstrate ∼10X aggregate improvement in energy efficiency, with a minimum energy of 0.36uJ/inference at 667MHz clock frequency. Compared to previously published spiking neural network accelerators, we demonstrate an improvement in energy efficiency of more than an order of magnitude, across a wide energy-accuracy trade-off range.
Band Alignment-Driven Oxidative Injury to the Skin by Anatase/Rutile Mixed-Phase Titanium Dioxide Nanoparticles Under Sunlight Exposure

Anatase/rutile mixed-phase titanium dioxide (TiO2) nanoparticles (NPs) have been found in cosmetics and cotton textiles. Once exposed to sunlight, mixed-phase TiO2 NPs are even more toxic to cells than pure phase NPs; however, the underlying mechanism remains unclear. Considering the unique anatase/rutile heterojunction structure existing in mixed-phase NPs, the potent toxicity of mixed-phase TiO2 NPs probably originates from the high reactive oxygen species (ROS) production because the anatase/rutile heterojunction is constituted by the staggered energy bands that facilitate the electron-hole separation at the interface due to the band alignment. In the present study, a library of mixed-phase TiO2 NPs with different anatase/rutile ratios was established to investigate the potential property-activity relationship and further clarify the underlying molecular mechanism. Under sunlight exposure, these mixed-phase TiO2 NPs could produce significant abiotic ROS and induce hierarchical oxidative stress to HaCaT skin cells and mice skin. The ROS magnitude and toxicity potential of these NPs were found to be proportional to their energy band bending (BB) levels. This means that the toxicity of mixed-phase TiO2 NPs can be correlated to their heterojunction density, and the toxicity potential of mixed-phase TiO2 NPs can be weighed by their BB levels.
Amphibians and reptiles of C. E. Miller Ranch and the Sierra Vieja, Chihuahuan Desert, Texas, USA

Abstract We report the occurrence of 50 species of amphibians and reptiles recently collected on C. E. Miller Ranch and the Sierra Vieja in the Chihuahuan Desert of Texas, USA and describe their perceived distribution and abundance across various habitat associations of the region. Our recent surveys follow intense, historic sampling of amphibians and reptiles from this region in 1948. Of the 50 species detected in recent surveys, six were not collected in 1948 and an additional three species documented in 1948 have yet to be detected in a 14-year period of recent surveys. Combining data from both historic and recent surveys, a total of 53 species of amphibians and reptiles are known from the ranch (11 amphibians, 42 reptiles). Land stewardship and conservation practices have likely contributed to the persistence of the majority of these species through time. Additionally, we discuss the status of amphibians and reptiles not collected during recent surveys and comment on potential species that have not yet been detected.
Calibration and testing of simulation models for evaluation of trench cap designs

A prototype decision support system (PDSS) using multi-objective decision theory and embedded simulation models is being developed to evaluate landfill cover designs for low-level radioactive waste disposal sites. To evaluate the performance of the PDSS, the simulation models, which are used to parameterize the decision model when data are not available, must be calibrated and tested. The two linked simulation models embedded in the PDSS are the HELP (hydrologic evaluation of landfill performance) and CREAMS (chemicals, runoff, and erosion from agricultural management systems) models. Data from a field demonstration study at Hill Air Force Base were used to calibrate the simulation models. The models were calibrated using water balance and erosion parameters for two alternative designs, a control soil cover and a modified USEPA Resource Conservation and Recovery Act design. Simulations were run using the calibrated model parameters for a 200-yr period to evaluate the long-term performance of the models. The progressive annual average for all of the output parameters was within the 95% confidence limits of the long-term mean by Year 60 for both of the cover designs evaluated. The results of the calibration and long-term evaluation of the simulation models were reasonable for the length of the datamore » set. To fully validate and test the simulation models, other data sets of landfill covers in a variety of climates are needed. 15 refs., 4 figs., 5 tabs. « less
The response of hepatocyte cell volume to hyperthermia and its role in oedema

A novel mathematical model for hepatocytes and surrounding volume is presented here; in addition to tracking ion transport and diffusion the new model allows for changing cell volume. Using temporally and spatially varying temperature as an input, this paper shows how differences between diffusion coefficients directly influence increases in cell volume. The multiscale nature of the model presents a possible link from established cellular equations to the observed clinical result of oedema present in thermal treatments of cancer.
Connected Morphological Operators for Binary Images

This paper presents a comprehensive discussion on connected morphological operators for binary images. Introducing a connectivity on the underlying space, every image induces a partition of the space in foreground and background components. A connected operator is an operator that coarsens this partition for every input image. A connected operator is called a grain operator if it has the following `local property'': the value of the output image at a given point $x$ is exclusively determined by the zone of the partition of the input image that contains $x$. Every grain operator is uniquely specified by two grain criteria, one for the foreground and one for the background components. A well-known criterion is the area criterion demanding that the area of a zone is not below a given threshold. The second part of the paper is devoted to connected filters and grain filters. It is shown that alternating sequential filters resulting from grain openings and closings are strong filters and obey a strong absorption property, two properties that do not hold in the classical non-connected case.