Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Tazemetostat as a Therapeutically Relevant Substance in Biliary Tract Cancer

Simple Summary Treating biliary tract cancer (BTC) successfully remains to be a difficult task. Standard therapeutic options encompass surgery, radiation and chemotherapy, but the median survival has not improved beyond one year. The reasons for this might be diagnosis at an already late stage and resistance towards current therapy. Therefore, novel strategies to combat this gastrointestinal disease need to be investigated. One alternative option may be to inhibit the enhancer of Zeste homolog 2 (EZH2), a histone-lysine-N-methyltransferase that was already shown to play a role in oncogenesis in BTC. Tazemetostat, an FDA-approved EZH2-inhibitor, seems to harbor promising anti-cancer properties in various tumor types. Therefore, in this study, we aim to investigate for the first time if tazemetostat might be a potential novel therapeutic strategy in biliary tract cancer. Abstract Biliary tract cancer (BTC) is a gastrointestinal malignancy associated with a poor survival rate. Current therapies encompass palliative and chemotherapeutic treatment as well as radiation therapy, which results in a median survival of only one year due to standard therapeutic ineffectiveness or resistance. Tazemetostat is an FDA-approved inhibitor of enhancer of Zeste homolog 2 (EZH2), a methyltransferase involved in BTC tumorigenesis via trimethylation of histone 3 at lysine 27 (H3K27me3), an epigenetic mark associated with silencing of tumor suppressor genes. Up to now, there are no data available regarding tazemetostat as a possible treatment option against BTC. Therefore, the aim of our study is a first-time investigation of tazemetostat as a potential anti-BTC substance in vitro. In this study, we demonstrate that tazemetostat affects cell viability and the clonogenic growth of BTC cells in a cell line-dependent manner. Furthermore, we found a strong epigenetic effect at low concentrations of tazemetostat, which was independent of the cytotoxic effect. We also observed in one BTC cell line that tazemetostat increases the mRNA levels and protein expression of the tumor suppressor gene Fructose-1,6-bisphosphatase 1 (FBP1). Interestingly, the observed cytotoxic and epigenetic effects were independent of the mutation status of EZH2. To conclude, our study shows that tazemetostat is a potential anti-tumorigenic substance in BTC with a strong epigenetic effect.
Investigation on the Photodegradation Stability of Acrylic Acid-Grafted Poly(butylene carbonate-co-terephthalate)/Organically Modified Layered Zinc Phenylphosphonate Composites

The application efficiency of biodegradable polymers used in a natural environment requires improved resistance to ultraviolet (UV) photodegradation. In this report, 1,6-hexanediamine modified layered zinc phenylphosphonate (m-PPZn), utilized as a UV protection additive for acrylic acid-grafted poly(butylene carbonate-co-terephthalate) (g-PBCT), was successfully fabricated and compared to the solution mixing process. Experimental data of both wide-angle X-ray diffraction and transmission electron microscopy reveal that the g-PBCT polymer matrix was intercalated into the interlayer spacing of m-PPZn, which was approximately delaminated in the composite materials. The evolution of photodegradation behavior for g-PBCT/m-PPZn composites was identified using Fourier transform infrared spectroscopy and gel permeation chromatography after being artificially irradiated by a light source. The change of carboxyl group produced via photodegradation was used to show the enhanced UV protection ability of m-PPZn in the composite materials. All results indicate that the carbonyl index of the g-PBCT/m-PPZn composite materials after photodegradation for 4 weeks was extensively lower than that of the pure g-PBCT polymer matrix. These findings were also supported by the decrease in the molecular weight of g-PBCT after photodegradation for 4 weeks, from 20.76% to 8.21%, with the loading of 5 wt% m-PPZn content. Both observations were probably owing to the better UV reflection ability of m-PPZn. This investigation shows, through typical methodology, a significant advantage of fabricating the photodegradation stabilizer to enhance the UV photodegradation behavior of the biodegradable polymer using an m-PPZn compared to other UV stabilizer particles or additives.
Executive Functions and Psychopathology Dimensions in Deficit and Non-Deficit Schizophrenia

This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits.
Covalent Organic Frameworks: From Structures to Applications

Three-dimensional covalent organic frameworks possess hierarchical nanopores, enormous surface areas with high porosity, and open positions. The synthesis of large crystals of three-dimensional covalent organic frameworks is a challenge, since different structures are generated during the synthesis. Presently, their synthesis with new topologies for promising applications has been developed by the use of building units with varied geometries. Covalent organic frameworks have multiple applications: chemical sensing, fabrication of electronic devices, heterogeneous catalysts, etc. We have presented the techniques for the synthesis of three-dimensional covalent organic frameworks, their properties, and their potential applications in this review.
The self-assembly of uniform heteroepitaxial islands

We present simulation for the morphological evolution of a Stranski–Krastanow system during the annealing process. By considering the strain energy, the surface-energy anisotropy, and the film–substrate interaction, the simulation demonstrates that the morphological evolution of the system can lead to an array of nearly uniform islands that is stable against coarsening. The stability results from the suppression of strain energy relaxation by strong surface-energy anisotropy and strong film–substrate interaction.
Reinvestigation of Rotational-Line Intensity Factors in Diatomic Spectra

The theory of the intensity factors of rotational lines in diatomic molecular spectra is reviewed with an emphasis on removing obscurities and resolving ambiguities that exist. For example, a unified intensity-factor sum rule is derived that is valid for all spin-allowed and spin-forbidden dipole transitions. Further, it is shown that the electronic transition moments can always be chosen to be real and that a few simple rules ensure the application of consistent phase factors.
The Great Scientists

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On Krull's conjecture concerning completely interally closed integrity domains, III

The case of partially ordered abelian groups being settled in Part I, let us turn to integrity domains; we want to obtain an integrity domain which is completely integrally closed but can never be expressed as an intersection of special valuation rings>. Our following construction depends however on that of Part I. Let A be a complete Boolean algebra satisfying the condition in Part I, Lemma 1; there be a countable set of non-atomic non-zero elements v in A so that for any a::>0 in A we have av for a suitable is. Denote its representation space by 9=B(A). Then the lattice-ordered abelian group La of continuous functions on I2, taking (rational) integers and + o as values and finite except on nowhere dense sets, cannot, as was shown in Part I, be represented faithfully by (finite)real-valued functions (over any space). Now, let K be a field, and consider, abstractly, variables (p) which are in one-one correspondence with the points p in 2. When {p, p, . , p} is a finite set of (distinct) points of 9, a polynomial of the variables (p), (p), . , x(p) over K will be called in the following a pp.p,-polynomial. Let {Ol, 02, --’, Or} be a subsystem of {pl, 02, . -. , P,}. A PIP2. p,-polynomial
Central Apnea in Patients with COVID-19 Infection

Background: The Coronavirus Disease 2019 (COVID-19) is a global pandemic that has killed over 1.5 million people worldwide. A constellation of multisystem involvement with SARS-CoV-2 has been reported. COVID-19 has been shown to affect the human nervous system, however, both the extent and severity of involvement have yet to be fully elucidated. In this manuscript, we aimed to better understand the effect of COVID-19 on neuro-respiratory status by studying COVID-19 patients who presented with central apnea. Methodology: We analyzed patient characteristics, clinical outcomes, laboratory results, and imaging results of three patients with symptomatic, PCR-proven COVID-19 and episodes of central apnea. Results: Of the three patients included in this study, two patients developed new central apnea, and one patient developed an exacerbation of underlying central apnea despite COVID-19 treatments with systemic steroids and remdesivir. All occurred, on average, 15 days after the onset of COVID-19 symptoms. At 1-year follow-up, all patients experienced complete resolution of apneic breathing. Conclusions: Physicians should be vigilant for the presentation of COVID-19 with central apnea. Central apnea may be a complication in patients with severe COVID-19 infection. More research is warranted to further understand this association.
Active control of turbulent boundary layers

An experimental investigation is made into the active control of the near-wall region of a turbulent boundary layer ($Re_\theta \,{=}\, 1960$) using a linear active control scheme. System identification in the boundary layer provides optimal transfer functions that predict the downstream characteristics of the streamwise velocity fluctuations. Enhanced detection techniques isolate the large-scale turbulent motion and improve the downstream correlations, resulting in greater controllability. The control is applied using a spanwise array of resonant synthetic jet actuators that introduce pairs of streamwise vortices into the flow. Control results show that a maximum reduction of 30% in the streamwise velocity fluctuations is achieved. This reduction is greatest at the point of optimization but spans a few hundred viscous lengths downstream of the actuator, about 50 viscous lengths in the wall-normal direction and 150 viscous lengths in the spanwise direction. The wall pressure fluctuation and the mean wall shear stress (measured approximately using mean velocity profiles near the wall) were reduced by 15% and 7% respectively. The bursting frequency, based on VITA event detection was also reduced by up to 23%.
Nonlinear Dynamics of Nearshore Irregular Waves: A Three-Dimensional Numerical Model and Its Verification

A three-dimensional numerical model based on the potential wave theory is developed for nonlinear irregular wave motion. The σ-transformation is employed to map the irregular and time-dependent domain of definition of the physical problem onto a strip of unit width so as to facilitate the implementation of the free surface and bottom boundary conditions. The finite difference method is used to solve the governing equations in the mapped coordinates. Non-reflective wave-generation is realized by combining virtual sources and a sponge layer. The numerical model is verified by the known solutions for nonlinear regular and irregular waves in water of constant depth. Standing waves in front of a vertical wall, runup of long waves on a sloping beach, and wave decomposition phenomenon over submerged bars are also studied. The model is also applied to a three-dimensional problem of nonlinear wave transformation over an elliptical shoal. The computational results are shown to agree well with the experimental data.
Walking with Different Insoles Changes Lower-Limb Biomechanics Globally in Patients with Medial Knee Osteoarthritis

Using insoles to modify walking biomechanics is of keen interest for the treatment of medial-compartment knee osteoarthritis. So far, insole interventions have focused on reducing the peak of the knee adduction moment (pKAM) and have led to inconsistent clinical outcomes. This study aimed to evaluate the changes in other gait variables related to knee osteoarthritis when patients walk with different insoles to provide insights into the necessity to enlarge the biomechanical analyses to other variables. Walking trials were recorded for 10 patients in four insole conditions. Changes among conditions were computed for six gait variables, including the pKAM. The associations between the changes in pKAM and the changes in the other variables were also assessed individually. Walking with different insoles had noticeable effects on the six gait variables, with high heterogeneity among patients. For all variables, at least 36.67% of the changes were of medium-to-large effect size. The associations with the changes in pKAM varied among variables and patients. In conclusion, this study showed that varying the insole could globally influence ambulatory biomechanics and that limiting measurement to the pKAM could lead to an important loss of information. Beyond the consideration of additional gait variables, this study also encourages personalized interventions to address inter-patient variability.
The Oscillatory Shrinkage in TRACE 195 Å Loops during a Flare Impulsive Phase

An altitude decrease of the flare loop-top X-ray sources during the early impulsive phase has recently been discovered with the RHESSI observations. The relevant evidence for the loop shrinkage has also recently been provided based on the Nobeyama radio images at 34 GHz. In this Letter, through analyzing the images observed with TRACE and RHESSI for the M2.5 flare on 2002 April 16, we present a new argument for the loop shrinkage: TRACE 195 Å loop shrinkage. The results show that in the early impulsive phase of about 5 minutes, the 195 Å loop in the running difference images shrank by about 30%, suggesting a mean apparent downward speed of approximately 15.3 km s-1. This speed is nearly the same as that deduced from the RHESSI 12-25 keV energy band but is greater than 7.7 km s-1 deduced from the RHESSI 6-12 keV energy band. The temporal behavior of 195 Å loop shrinkage is consistent with that revealed from the RHESSI X-ray sources. Further study shows that the TRACE 195 Å loop shrinkage is in the form of an oscillation, with a period of about 150 s and an amplitude of about 300 km. We discuss this oscillatory shrinkage with respect to a theoretical reconnection model.
Strong Variability in the Thermal Structure of Tibetan Lithosphere

We present a model of thermal lithospheric thickness (the depth where the geotherm reaches a temperature of 1300°C) and surface heat flow in Tibet and adjacent regions based on a new thermal‐isostasy method. The method accounts for crustal density heterogeneity, is free from any assumption of a steady‐state lithosphere thermal regime, and assumes that deviations from crustal Airy‐type isostasy are caused by lithosphere thermal heterogeneity. We observe a highly variable lithospheric thermal structure which we interpret as representing longitudinal variations in the northern extent of the subducting Indian plate, southward subduction of the Asian plate beneath central Tibet, and possible preservation of fragmented Tethyan paleo‐slabs. Cratonic‐type cold and thick lithosphere (200–240 km) with a predicted surface heat flow of 40–50 mW/m2 typifies the Tarim Craton, the northwest Yangtze Craton, and most of the Lhasa Block that is likely refrigerated by underthrusting Indian lithosphere. We identify a “North Tibet anomaly” with thin (<80 km) lithosphere and high surface heat flow (>80–100 mW/m2). We interpret this anomaly as the result of removal of lithospheric mantle and asthenospheric upwelling at the junction of the Indian and Asian slabs with opposite subduction polarities. Other parts of Tibet typically have intermediate lithosphere thickness of 120–160 km and a surface heat flow of 45–60 mW/m2, with patchy anomalies in eastern Tibet. While different uplift mechanisms for Tibet predict different lithospheric thermal regimes, our results in terms of a highly variable thermal structure beneath Tibet suggest that topographic uplift is caused by an interplay of several mechanisms.
Surface oxidation of Permalloy thin films

The chemical and magnetic structures of oxides on the surface of Permalloy Ni{sub 81}Fe{sub 19} films were investigated as functions of annealing time with x-ray and polarized neutron reflectometry. For annealing times of less than one hour, the oxide consisted of a 1.5-nm-thick layer of NiO on an Fe oxide layer that was in contact with Permalloy. The Fe oxide thickness increases with annealing time with a parabolic rate constant of 10{sup -18} cm{sup 2} s{sup -1} (for an annealing temperature of 373 K). The growth of the oxide layer is limited by the rate at which oxygen appears below the NiO layer. No portion of the oxide region was found to be ferromagnetically ordered for films annealed less than one hour. The growth of the Fe oxide region is well correlated with the measured increase of the second-order magnetic susceptibility for similarly prepared samples.
Knockdown of Bmp1 and Pls1 Virulence Genes by Exogenous Application of RNAi-Inducing dsRNA in Botrytis cinerea

Botrytis cinerea is a pathogen of wide agronomic and scientific importance partly due to its tendency to develop fungicide resistance. Recently, there has been great interest in the use of RNA interference as a control strategy against B. cinerea. In order to reduce the possible effects on non-target species, the sequence-dependent nature of RNAi can be used as an advantage to customize the design of dsRNA molecules. We selected two genes related to virulence: BcBmp1 (a MAP kinase essential for fungal pathogenesis) and BcPls1 (a tetraspanin related to appressorium penetration). After performing a prediction analysis of small interfering RNAs, dsRNAs of 344 (BcBmp1) and 413 (BcPls1) nucleotides were synthesized in vitro. We tested the effect of topical applications of dsRNAs, both in vitro by a fungal growth assay in microtiter plates and in vivo on artificially inoculated detached lettuce leaves. In both cases, topical applications of dsRNA led to gene knockdown with a delay in conidial germination for BcBmp1, an evident growth retardation for BcPls1, and a strong reduction in necrotic lesions on lettuce leaves for both genes. Furthermore, a strongly reduced expression of the BcBmp1 and BcPls1 genes was observed in both in vitro and in vivo experiments, suggesting that these genes could be promising targets for the development of RNAi-based fungicides against B. cinerea.
Assessment of Effects of Rosemary Essential Oil on the Kidney Pathology of Diabetic Adult Male Albino Rats

Background Diabetic nephropathy is a severe condition that causes persistent kidney problems and chronic renal failure. Rosemary (Rosmarinus officinalis L) is widely recognized for its antioxidant, antidiabetic, anti-inflammatory, antithrombotic, hepatoprotective, and anticancer activities. The current study evaluated rosemary essential oil (REO) effects on biochemical, histological, and immunohistochemical kidney alterations in streptozotocin (STZ)-induced diabetic rats and compared these effects with those of insulin and both combined. Methods We randomly distributed 36 adult albino rats into 6 groups: normal control (non-diabetic), diabetic (streptozotocin, 55 mg/kg, intraperitoneal), diabetic insulin-treated (Lantus insulin 2 units/day, SC), diabetic REO-treated (REO, 10 ml, nasogastric gavage), and diabetic insulin & REO-treated groups. Biochemical, histological, and immunohistochemical analyses were conducted. Results The diabetic group revealed a substantial increase in blood glucose, urea, creatinine, and uric acid, as well as malondialdehyde (MDA) and catalase (CAT) concentrations in kidney homogenates, high score of tubular injury, and increased glomerulosclerosis, along with marked reduction of total glutathione (GSH) and superoxide dismutase (SOD) when compared to control. Evident improvement was detected in rats treated with REO as it demonstrated antioxidant, anti-inflammatory, anti-apoptotic, pro-proliferative, and mild anti-hyperglycemic effects on diabetic rats, reducing the kidney damage caused by diabetes. Combined insulin and REO restored normal blood glucose, renal excretory function tests, antioxidant markers, and renal cortex histology. Conclusion The data presented in the current study's in vivo animal model suggests that REO supplementation has beneficial nephroprotective effects on the structural and, to a lesser extent, functional levels of diabetic rats. Furthermore, the detected nephroprotective effects of insulin and REO combined are superior to those of either administered alone. However, further studies are needed to evaluate these conclusions in humans further.