Miracle-dz/UniFAR-FTUs huggingface dataset:
BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications

The mammalian bromodomain and extra-terminal domain (BET) family of proteins consists of four conserved members (Brd2, Brd3, Brd4, and Brdt) that regulate numerous cancer-related and immunity-associated genes. They are epigenetic readers of histone acetylation with broad specificity. BET proteins are linked to cancer progression due to their interaction with numerous cellular proteins including chromatin-modifying factors, transcription factors, and histone modification enzymes. The spectacular growth in the clinical development of small-molecule BET inhibitors underscores the interest and importance of this protein family as an anticancer target. Current approaches targeting BET proteins for cancer therapy rely on acetylation mimics to block the bromodomains from binding chromatin. However, bromodomain-targeted agents are suffering from dose-limiting toxicities because of their effects on other bromodomain-containing proteins. In this review, we provided an updated summary about the evolution of small-molecule BET inhibitors. The design of bivalent BET inhibitors, kinase and BET dual inhibitors, BET protein proteolysis-targeting chimeras (PROTACs), and Brd4-selective inhibitors are discussed. The novel strategy of targeting the unique C-terminal extra-terminal (ET) domain of BET proteins and its therapeutic significance will also be highlighted. Apart from single agent treatment alone, BET inhibitors have also been combined with other chemotherapeutic modalities for cancer treatment demonstrating favorable clinical outcomes. The investigation of specific biomarkers for predicting the efficacy and resistance of BET inhibitors is needed to fully realize their therapeutic potential in the clinical setting.
Trust and trust-linked elements in the formation of tourism networks in Brazil and Spain

While there is evidence of the positive influence of trust in cooperation development, in situations where trust is unfeasible, trust-linked elements are needed. In this investigation, trust-linked elements are considered to be contracts, supporting institutions (SIs), and reciprocity. This research aims to determine the role of trust and/or trust-linked elements in the formation of tourism business networks of Brazil and Spain. A quantitative study, using structural equation modelling, was carried out on a sample of 307 lodging companies. The results show that trust remains a key element in the composition of both Brazilian and Spanish business networks, although trust alone may not sufficiently explain collaboration in the tourism industry. This strengthens the argument for employing trust-linked elements to promote cooperation. Contracts and SIs substitute trust, whereas reciprocity complements it. SIs, in particular, play a crucial role in fostering cooperation, without requiring trust or incurring transaction costs, which is a less obvious but nonetheless important service. Networks in tourism destinations are often diverse and adaptable, suggesting that cooperation is idiosyncratic and an ongoing, dynamic process. This investigation concludes that decision-making for enhancing networking capabilities must consider various possibilities aligned with the social embeddedness of the companies in the corresponding tourism destination.
Ecotonic Communities of Diatoms in the Southeastern Part of the Kamchatka Peninsula

Data about the ecotonic diatom communities of the Kamchatka Peninsula, a unique territory with strong volcanic activity, are very limited. We aimed to investigate diatom algae of the ecotones in the southeastern part of Kamchatka, including the Paratunka river valley, at the foot of the Vachkazhets volcano, and the bank of the Bystraya river. In total, 55 taxa were identified. The most diverse were the flora of the Paratunka river, with 31 taxa. Near the Bystraya river, 26 taxa were identified. Near the Vachkazhets volcano, 18 taxa were identified. Fragilariforma virescens, Planothidium lanceolatum, Pinnularia cf. subcapitata, Halamphora normanii, Nitzschia palea, and Eunotia exigua were the dominant species in the studied ecosystems, with the maximum abundance score. Pinnularia cf. subcapitata and Planothidium lanceolatum were found in all ecotones. In the studied habitats, small indifferent alkaliphilic cosmopolitan species prevailed. Our study revealed that the diatom species composition of the Kamchatka ecotones reflects their adaptability to survive in the extreme conditions of volcanic substrates. The results contribute to our knowledge of the ecology and biogeography of a number of diatom taxa.
Formation of inhomogeneity in drop concentration induced by the inertia of drops falling in a turbulent flow, and the influence of the inhomogeneity on the drop‐spectrum broadening

The mechanisms of drop‐concentration inhomogeneity formation are studied using both a numerical simulation with a model of isotropic and homogeneous turbulence, and analytical methods. It is shown that atmospheric turbulence can create a significant drop‐concentration inhomogeneity due to the effects of drop inertia. Two types of area in the turbulent flow are revealed. Drops tend to leave the areas of ‘drop vortices’ and collect within the zones out of the vortices. As a result, the zones of drop‐track collection turn out to be the zones of enhanced drop concentration. the rate of concentration enhancement is studied for drops of different sizes using the Monte Carlo method. It is shown that the drop flux velocity divergence and droplet‐concentration variations reach their maximum at 100 μm drop radius. Zones of enhanced drop concentrations are stretched along the drop tracks. Characteristic scales of drop‐concentration fluctuations along the drop tracks are of the order of several metres or even a few tens of metres. Across the drop tracks, the characteristic scale of concentration pulsations is of the order of a few centimetres.
Refining Our Understanding of Late Cretaceous–Paleogene Evolution within the Monocot Family Araceae: Appianospadix bogneri gen. et sp. nov.

Premise of research. Two permineralized inflorescences have been found in calcium carbonate concretions from the Eocene Appian Way locality on Vancouver Island, British Columbia, increasing sampling density and helping clarify the pattern of phylogeny for Alismatalean monocots. Methodology. Serial sections of specimens were prepared by the cellulose acetate peel technique and studied with light microscopy. Phylogenetic analyses using a morphological matrix of living and fossil Araceae and Acoraceae were performed using TNT version 1.5 to help establish relationships of the fossil inflorescences. Pivotal results. Inflorescences are cylindrical spikes, >37 mm long and 8.1 mm wide, with a peduncle at least 14.5 mm long, bearing numerous helically arranged, bisexual sessile flowers with hooded tepals. Fruits are trilocular, with basal axile placentation and one seed per locule. Remnants of probable stamens are present in most flowers. Conclusions. Flower structure was compared to those of other petalloid, spicate, bisexual flowers in the monocot families Acoraceae and Araceae (Alismatales). The number of carpels is similar to that in Acorus (Acoraceae) and Spathiphyllum (Araceae, Monsteroideae) and some Pothoideae. Single-seeded ovaries are common in Araceae, while the locules in Acorus contain several apically attached seeds. Phylogenetic analyses place Appianospadix in Proto-Araceae near the base of the aroid tree. This inflorescence with a unique combination of characters is described as Appianospadix bogneri, a new genus and species of Alismatales (family: Araceae).
An automatic band selection algorithm based on connection centre evolution

ABSTRACT The characteristics of high dimensionality, strong band correlation, and high information redundancy make band selection become a necessary step for efficient processing of hyperspectral images. In this paper, a new band selection method based on connection centre evolution (CCE) is proposed, named -nearest neighbour CCE band selection (NNCCEBS). First, according to CCE, we measure the band similarity under different observation scales by iteratively calculating the connectivity at different scales. Therefore, NNCCEBS can achieve multi-scale band selection, and is able to complete it at one time. Next, to avoid the selected bands being aggregated, an -nearest neighbour similarity matrix is introduced, which only retains the connectivity of -nearest bands for a band. By doing so, the new method is less sensitive to the parameter settings, and can select more accurate band centres. Experiments on real hyperspectral datasets prove the effectiveness of our method.
Sum-Rate Maximization of IRS-Aided SCMA System

We study an intelligent reflecting surface (IRS)-aided downlink sparse code multiple access (SCMA) system for massive connectivity in future machine-type communication networks. Our objective is to maximize the system sum-rate subject to the constraint of minimum user data rate, the total power of base station, SCMA codebook structure, and IRS channel coefficients. To this end, a joint optimization problem involving IRS phase vector, factor graph matrix assignment, and power allocation problem is formulated, which is non-convex in nature. This problem is solved by developing an alternating optimization (AO) algorithm. A key idea is to first divide the formulated non-convex problem into three subproblems (i.e., factor graph matrix assignment, power allocation, and phase vector of IRS) and then tackle them iteratively. The validity of the proposed schemes is shown using the simulation results. Moreover, compared to the SCMA system without IRS, a significant performance improvement in the IRS-aided SCMA system is shown in terms of achievable sum-rate.
Convex dynamics with constant input

Abstract In Adler et al [Convex dynamics and applications. Ergod. Th. & Dynam. Sys.25 (2005), 321–352] certain piecewise linear maps were defined in terms of a convex polytope. When the convex polytope is a simplex, the resulting map has a dual nature. On one hand it is defined on ℝN and acts as a piecewise translation. On the other it can be viewed as a translation on the N-torus. What relates its two roles? A natural answer would be that there exists an invariant fundamental set into which all orbits under piecewise translation eventually enter. We prove this for N=1 and for acute and right triangles—i.e. non-obtuse triangles. We leave open the case of obtuse triangles and higher-dimensional simplices. Another question not treated is the connectivity of the invariant fundamental sets which arise.
An Epidemiological Study of the Quality of Life of Children With Beta-Thalassemia Major (β-TM) and Its Correlates in Kolkata, West Bengal, India

Background and objectives In contrast to their peers who are healthy, children with thalassemia disease are likely to have a lower quality of life (QoL). Knowledge of attributes affecting the QoL of thalassemic children may help identify key areas of intervention to improve it. Thus, the current study was envisioned to find out the quality of life (QoL) of children with beta-thalassemia major (β-TM) and its various correlates. Methods Between May 2016 and April 2017, an institution-based cross-sectional observational study was conducted in the thalassemia unit of Calcutta National Medical College and Hospital (CNMC&H), Kolkata, West Bengal, India. During the study period, 328 β-TM children and their carers were interviewed using a structured schedule. Results In the final multivariable logistic regression model, thalassemic children who were residing in an urban area (adjusted odds ratio (AOR) (95% confidence interval (CI)): 2.1 (1.1-4.0)), had mothers with a higher educational level (middle and above) (AOR (95%CI): 2.1 (1.1-4.0)), had working parents (AOR (95%CI): 2.7 (1.2-6.3)), had no family history of thalassemia (AOR (95%CI): 3.5 (1.6-8.0)), received less number of blood transfusion in the previous year (<12) (AOR (95%CI): 2.1(1.1-4.2)), had higher pre-transfusional hemoglobin (Hb) level (AOR (95%CI): 1.7(1.1-2.6)), had no transfusion-transmitted infections (TTIs) (AOR (95%CI): 2.8 (1.5-5.2)), had higher body mass index (BMI) Z score (AOR (95%CI): 1.6 (1.1-2.2)), and had higher Carer Quality of Life (CarerQoL) score (>5) (AOR (95%CI): 3.2 (1.6-6.2)) were more likely to have favorable QoL (Pediatric Quality of Life Inventory (PedsQL) score > 54.3). Interpretation and conclusions The QoL of the study participants was significantly correlated with their carers’ CarerQoL, mother’s educational level, parent’s working status, place of residence, family history of the disease, blood transfusion frequency, pre-transfusional Hb level, and nutritional and comorbidity status.
A Monte Carlo method for sensitivity analysis and parametric optimization of nonlinear stochastic systems

For high-dimensional or nonlinear problems there are serious limitations on the power of available computational methods for the optimization or parametric optimization of stochastic systems. The paper develops an effective Monte Carlo method for obtaining good estimators of systems sensitivities with respect to system parameters under quite general conditions on the systems and cost functions. The value of the method is borne out by numerical experiments, and the computational requirements are favorable with respect to competing methods when the dimension is high or the nonlinearities “severe. ” The method is a type of “derivative of likelihood ratio” method. Jump-diffusion, functional diffusion, and reflected diffusion models of broad types are covered by the basic technique (e.g., the type of limit model that arises in the analysis of queueing systems under heavy traffic, where the boundary reflection conditions are discontinuous). For a wide class of problems, the cost function or dynamics need not be .
Dynamic Response of a Cup Anemometer

Abstract The dynamic response of a cup anemometer is studied, based on an equation of motion. Torque acting on the anemometer is shown to be different in the accelerating and the decelerating states of rotation. The values of the coefficients in the equation of motion are also different. They can be determined by simple experiments. The fluctuation of natural wind measured by a cup anemometer is compared with that observed by a sonic anemometer as a reference sensor. A new reduction method for a cup anemometer record for fluctuating wind is proposed and tested.
Estimation and Inference in Time Series with Omitted I(1) Variables

Standard cointegration analysis yields spurious results when relevant I(1) variables are omitted from the model. As an alternative, an unobserved components approach is proposed where the error term is modelled as the sum of a transitory and a random walk component. The latter should capture omitted I(1) variables and is allowed to be correlated with the observed I(1) variables. Provided that the model is correctly specified and identified, the long-run relation between the non-cointegrated variables can be estimated consistently with maximum likelihood using the Kalman filter. The robustness of this approach to the integration properties of the error terms is supported for small samples via an extensive Monte Carlo study. The proposed methodology is applied to testing purchasing power parity.
Further Generalizations of Convexity in Mathematical Programming

The Kuhn-Tucker conditions for the existence of solutions to inequality constrained minimization problems are sufficient conditions when all the functions involved are convex. Various concepts such as pseudo-convexity and quasi-convexity have been introduced for the purpose of weakening this limitation of convexity in mathematical programming. Still wider classes of functions are introduced in this paper and applied in Kunh-Tucker theory and in duality theory.
Role of viscosity stratification in the stability of two-layer flow down an incline

The stability of the flow of two layers of viscous liquids down an incline is investigated. The problem is governed by two competing long-wavelength modes associated with the surfaces. One mode, calling it the first mode, is faster than the second one. When the two layers have the same coefficient of dynamic viscosity, the second mode was found earlier by the author to be the governing mode for most cases. The situation is greatly altered when viscosity is not the same for the two layers. The second mode is dramatically stabilized for the range of viscosity ratio, m, less than unity, and the first mode is now generally the governing mode in that range. The overall effect is stabilizing compared with m = 1. A relative stability index is also introduced to compare the result with that of the homogeneous case. It is found that the presence of the upper layer is generally destabilizing compared with that of a homogeneous fluid of the same total depth.
Salivary 1,5-Anhydroglucitol and its Correlation with Postprandial Hyperglycemia: Development and Validation of a Novel Assay

Background: Saliva has the potential to be used as a noninvasive sample for testing hyperglycemia in diabetes mellitus. Serum 1,5-anhydroglucitol (1,5-AG) decreases with an increase in blood sugar >180 mg/dl. We hypothesized that salivary 1,5-AG can be used to identify blood sugar higher than 180 mg/dl using a novel biochemical method. Aim: This study aimed to develop a novel biochemical method for serum and salivary assessment of 1,5-AG and assess its correlation with postprandial blood sugar (PPBS) >180 mg/dl. Methodology: The study comprised 45 controls (healthy individuals) and 45 cases (type 2 diabetic patients with PPBS >180 mg/dl). Blood and salivary samples were collected according to the study protocol. A new method was developed for the quantification of 1,5-AG in serum and saliva using liquid chromatography–mass spectrometry. Results: The value of serum (mean –22.19 μg/ml and median –22.12 μg/ml) and salivary (mean –0.124 μg/ml and median –0.088 μg/ml) 1,5-AG was higher in healthy individuals compared to corresponding serum (mean –3.89 μg/ml and median –2.52 μg/ml) and salivary (mean –0.025 μg/ml and median – 0.025 μg/ml) levels in diabetics with PPBS >180 mg/dl. In diabetics, a significant negative correlation was noticed with PPBS levels and 1,5-AG levels in serum and saliva. Salivary 1,5-AG level <0.054 μg/ml had an 86.4% sensitivity and 87.2% specificity in predicting a blood sugar value >180 mg/dl. Conclusion: The results of our study suggest that the short-term glycemic marker 1,5-AG can be detected in saliva and can be useful as an adjunct marker in monitoring of glycemic status in diabetic patients.
Addressing the withdrawal of playtime: a collaborative action research project

ABSTRACT Despite evidence for the importance of playtime for children, the use of the withdrawal of playtime is a sanction that is used throughout schools in the UK. In light of this, there have been recent arguments highlighting the need to explore alternatives to this sanction in order to protect opportunities for playtime. This exploratory action research study included an initial focus group and multiple psychological consultations with teachers in a single setting to collaboratively explore and review potential alternatives. Findings include teachers wanting to address behaviours that often result in the withdrawal of playtime, and strategies to address these were co-constructed and implemented. Other findings included contextual barriers to stopping the use of withdrawing playtime, such as curriculum constraints, as well as facilitative aspects to stopping the withdrawal of playtime. Further implications for EP and school practice and research, as well as limitations, are discussed.
Increasing the intensity of an induction accelerator and reduction of the beam breakup instability

A 7 cm cathode has been deployed for use on a 3.8 MV, 80 ns (FWHM) Blumlein, to increase the extracted electron current from the nominal 1.7 to 2.9 kA. The intense relativistic electron bunch is accelerated and transported through a nested solenoid and ferrite induction core lattice consisting of 64 elements, exiting the accelerator with a nominal energy of 19.8 MeV. The principal objective of these experiments is to quantify the space-charge limitations on the beam quality, its coupling with the beam breakup (BBU) instability, and provide an independent validation of the BBU theory in a higher current regime, I > 2 kA. Time resolved centroid measurements indicate a reduction in BBU > 10 × with simply a 50% increase in the average B-field used to transport the beam through the accelerator. A qualitative comparison of experimental and calculated results are presented, which include time resolved current density distributions, radial BBU amplitude relative to the calculated beam envelope, and frequency analyzed BBU amplitude with different accelerator lattice tunes.
Radiation Hard Hybrid Pixel Detectors, and a bbbar Cross Section Measurement at the CMS Experiment

Measurements of heavy flavor quark production at hadron colliders provide a good test of the perturbative quantum chromodynamics (pQCD) theory. It is also essential to have a good understanding of the heavy quark production in the search for new physics. Heavy quarks contribute to backgrounds and signals in measurements of higher mass objects, such as the Higgs boson. A key component to each of these measurements is good vertex resolution. In order to ensure reliable operation of the pixel detector, as well as confidence in the results of analyses utilizing it, it is important to study the effects of the radiation on the detector. In the first part of this dissertation, the design of the CMS silicon pixel detector is described. Emphasis is placed on the effects of the high radiation environment on the detector operation. Measurements of the charge collection efficiency, interpixel capacitance, and other properties of the pixel sensors as a function of the radiation damage are presented. In the second part, a measurement of the inclusive bb̄ production cross section using the b → μD0X,D0 → Kπ decay chain with data from the CMS experiment at the LHC is presented. The data were recorded with the CMS experiment at the Large Hadron Collider (CERN) in 2010 using unprescaled single muon triggers corresponding to a total luminosity of 25 pb−1. The differential cross section is measured for p μ T > 6 GeV/c and |η| < 2.4 corresponding to a total cross section of 4.36±0.54(stat.) −0.25(sys.)±0.17(B)±0.23(L) μ b.
Are north‐south aligned auroral structures an ionospheric manifestation of bursty bulk flows?

Bursty Bulk Flow (BBF) events are an important means of plasma transport in the Earth's magnetotail during substorms. While several studies have been performed using in‐situ plasma and field data to determine the characteristics of BBFs, remarkably little attention has been paid to the question of whether or not these events also manifest themselves in the auroral ionosphere. In this paper, we present observations from the Viking UV imager, and the Los Alamos National Laboratory geosynchronous energetic particle detectors that strongly suggest that the north‐south aligned structures formed impulsively and repetitively during the expansion phase of substorms may be an ionospheric manifestation of BBFs.