Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of Deferasirox (Exjade®) in Modulation of Iron Overload in Patients with β-Thalassemia Intermedia

Abstract Because of insufficient erythropoiesis, peripheral hemolysis and increased gastrointestinal iron absorption, iron overload is still a matter of debate in β-thalassemia intermedia (β-TI) patients, which can be overcome using iron chelators. However, data on use of iron chelators in β-TI patients is highly restricted. The aim of this study was to evaluate the efficacy of oral administration of deferasirox (Exjade® or DFX) by assessment of serum ferritin levels in β-TI patients. In this quasi-experimental study, 50 β-TI patients with serum ferritin levels >1000 ng/mL were selected and received oral DFX for 12 consecutive months. Iron overload was measured by checking serum ferritin levels every 2 months and the results were compared with the baseline level. The mean serum ferritin was decreased during 1 year of chelation therapy without any toxic effect. Although the difference between baseline ferritin and ferritin levels at the end of second month was not remarkable (p = 0.88), a significant reduction in serum ferritin was observed after 4 (p = 0.01), 6 (p = 0.001), 8 (p < 0.001), 10 (p < 0.001) and 12 months (p < 0.001) of chelation therapy compared to its baseline levels. There was no correlation between baseline ferritin levels and age (p = 0.574). In addition, no statistically significant difference was observed about change in serum ferritin levels after 6 and also 12 months of therapy between patients who had undergone splenectomy and those who did not (p = 0.796 and 0.859, respectively). Iron chelation therapy with DFX is safe and effective in reducing serum ferritin levels in β-TI patients who suffer from side effects of iron overload.
One co evolutio Structure and function in mammalian societies

Traditional interpretations of the evolution of animal societies have suggested that their structure is a consequence of attempts by individuals to maximize their inclusive fitness within constraints imposed by their social and physical environments. In contrast, some recent re-interpretations have argued that many aspects of social organization should be interpreted as group-level adaptations maintained by selection operating between groups or populations. Here, I review our current understanding of the evolution of mammalian societies, focusing, in particular, on the evolution of reproductive strategies in societies where one dominant female monopolizes reproduction in each group and her offspring are reared by other group members. Recent studies of the life histories of females in these species show that dispersing females often have little chance of establishing new breeding groups and so are likely to maximize their inclusive fitness by helping related dominants to rear their offspring. As in eusocial insects, increasing group size can lead to a progressive divergence in the selection pressures operating on breeders and helpers and to increasing specialization in their behaviour and life histories. As yet, there is little need to invoke group-level adaptations in order to account for the behaviour of individuals or the structure of mammalian groups.
Mapping Transcription Factor Networks By Comparing Tf Binding Locations To Tf Perturbation Responses

Background A transcription-factor (TF) network map indicates the direct, functional targets of each TF -- the genes it regulates by binding to their cis-regulatory DNA. Data on the genomic binding locations of each TF and the transcriptional responses to perturbations of its activity, such as overexpressing it, could support TF network mapping. Systematic data sets of both types exist for yeast and for human K562 and HEK293 cells. Results In previous data, most TF binding sites appear to be non-functional, so one cannot take the genes in whose promoters a TF binds as its direct, functional (DF) targets. Taking the genes that are both bound by a TF and responsive to a perturbation of it as its DF targets (intersection algorithm) is also not safe, as we show by deriving a new lower bound on the expected false discovery rate of the intersection algorithm. When there are many non-functional binding sites and many indirect targets, non-functional sites are expected to occur in the cis-regulatory DNA of indirect targets by chance. Dual threshold optimization, a new method for setting significance thresholds on binding and response data, improves the intersection algorithm, as does post-processing perturbation-response data with NetProphet 2.0. A comprehensive new data set measuring the transcriptional response shortly after inducing overexpression of a TF also helps, as does transposon calling cards, a new method for identifying TF binding locations. Conclusions The combination of dual threshold optimization and NetProphet greatly expands the high-confidence TF network map in both yeast and human. In yeast, measuring the response shortly after inducing TF overexpression and measuring binding locations by using transposon calling cards improve the network synergistically.
Allosteric Model of Maraviroc Binding to CC Chemokine Receptor 5 (CCR5)*

Maraviroc is a nonpeptidic small molecule human immunodeficiency virus type 1 (HIV-1) entry inhibitor that has just entered the therapeutic arsenal for the treatment of patients. We recently demonstrated that maraviroc binding to the HIV-1 coreceptor, CC chemokine receptor 5 (CCR5), prevents it from binding the chemokine CCL3 and the viral envelope glycoprotein gp120 by an allosteric mechanism. However, incomplete knowledge of ligand-binding sites and the lack of CCR5 crystal structures have hampered an in-depth molecular understanding of how the inhibitor works. Here, we addressed these issues by combining site-directed mutagenesis (SDM) with homology modeling and docking. Six crystal structures of G-protein-coupled receptors were compared for their suitability for CCR5 modeling. All CCR5 models had equally good geometry, but that built from the recently reported dimeric structure of the other HIV-1 coreceptor CXCR4 bound to the peptide CVX15 (Protein Data Bank code 3OE0) best agreed with the SDM data and discriminated CCR5 from non-CCR5 binders in a virtual screening approach. SDM and automated docking predicted that maraviroc inserts deeply in CCR5 transmembrane cavity where it can occupy three different binding sites, whereas CCL3 and gp120 lie on distinct yet overlapped regions of the CCR5 extracellular loop 2. Data suggesting that the transmembrane cavity remains accessible for maraviroc in CCL3-bound and gp120-bound CCR5 help explain our previous observation that the inhibitor enhances dissociation of preformed ligand-CCR5 complexes. Finally, we identified residues in the predicted CCR5 dimer interface that are mandatory for gp120 binding, suggesting that receptor dimerization might represent a target for new CCR5 entry inhibitors.
Molecular decomposition and a class of Fourier multipliers for bi-parameter modulation spaces

In this paper, we investigate bi-parameter modulation spaces on the product of two Euclidean spaces \begin{document}$ \mathbb{R}^{n} $\end{document} and \begin{document}$ \mathbb{R}^{m} $\end{document} via uniform decompositions of each factor. A molecular decomposition of these bi-parameter spaces are given, which generalizes the related single-parameter result of Kobayashi and Sawano [ 33 ]. Furthermore, we prove the boundedness of a class of Fourier multipliers on bi-parameter modulation spaces, generalizing the results of Benyi et al. [ 2 ] and Feichtinger and Narimani [ 17 ].
Fullerol antagonizes dexamethasone‐induced oxidative stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem cell

Increased oxidative stress is currently considered as a crucial cause of corticosteroid‐induced osteonecrosis. The aim of this study was to evaluate the effect of fullerol, a powerful antioxidant, on adipogenic and osteogenic differentiation of a mouse bone marrow derived multipotent cell line, D1. Upon treatment with dexamethasone, D1 cells containing lipid vesicles were distinguishable from the surrounding cells by Oil Red O staining at day 21. Simultaneous treatment of dexamethasone with antioxidant glutathione or fullerol decreased the number of cells containing lipid vesicles. Treatment with dexamethasone for 7 days resulted in a significant increase in adipogenic markers peroxisome proliferator‐activated receptor gamma and adipocyte protein 2 gene expression and decrease in expression of osteogenic markers runt‐related transcription factor 2 and osteocalcin and antioxidative enzymes superoxide dismutase and catalase as revealed by quantitative real‐time PCR. While glutathione and fullerol both were able to antagonize the effects of dexamethasone, fullerol had a greater effect than glutathione. Staining with a fluorescent dye CM‐H2DCFDA as indicator of cellular reactive oxygen species revealed that the percentage of positively stained cells increased after dexamethasone treatment, and addition of fullerol attenuated this activity. These results indicated that fullerol inhibited adipogenesis and simultaneously enhanced osteogenesis by marrow mesenchymal stem cells possibly through elimination of cellular reactive oxygen species. The results indicated that fullerol can potentially be used for prevention and treatment of corticosteroid‐induced osteonecrosis. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1051–1057, 2012
When can A Clonal Organism Escape Senescence?

Some clonal organisms may live for thousands of years and show no signs of senescence, while others consistently die after finite life spans. Using two models, we examined how stage‐specific life‐history rates of a clone's modules determine whether a genetic individual escapes senescence by replacing old modules with new ones. When the rates of clonal or sexual reproduction and survival of individual modules decline with age, clones are more likely to experience senescence. In addition, the models predict that there is a greater tendency to find senescence in terms of a decline in the rate of sexual reproduction with clone age than in terms of an increase in the probability of clone mortality, unless rates of sexual reproduction increase dramatically with module stage. Using a matrix model modified to represent the clonal lifestyle, we show how a trade‐off between sexual and clonal reproduction could result in selection for or against clonal senescence. We also show that, in contrast to unitary organisms, the strength of selection on life‐history traits can increase with the age of a clone even in a growing population, countering the evolution of senescence.
Java Performance Tuning

From the Publisher: No matter what language they're programming in, developers always wish things would run faster! Especially when writing mission-critical applications, no one wants to be limited by their programming environment. Java Performance Tuning provides all the details a developer needs to know to "performance tune" any type of Java program and make Java code run significantly faster. Java Performance Tuning contains step-by-step instructions on all aspects of the performance tuning process, right from such early considerations as setting goals, measuring performance, and choosing a compiler. Extensive examples for tuning many parts of an application are described in detail, and any pitfalls are identified. The book also provides performance tuning checklists that enable developers to make their tuning as comprehensive as possible. Java Performance Tuning is a book for developers who are ready to "roll up their sleeves" and examine their code in detail in order to apply different tuning techniques to produce the best possible result. The book shows how to: Create and plan a tuning strategy Avoid performance penalties from inefficient code Minimize the number of objects a program creates Improve the behavior of loops and switches Use threads effectively About the Author Jack Shirazi is an independent consultant. He was an early adopter of Java, and for the past few years he has consulted, mainly for the financial sector, focusing on Java performance. Before using Java, Jack spent many years tuning smalltalk applications. Jack is also pleased to have contributed to some of the core Perl 5 modules.
Impaired Regulation of Hepatic Fructose-1,6-Bisphosphatase in the New Zealand Obese Mouse Model of NIDDM

The New Zealand obese mouse, a model of NIDDM, is characterized by hyperglycemia, hyperinsulinemia, and hepatic and peripheral insulin resistance. The aim of this study was to investigate the biochemical basis of hepatic insulin resistance in NZO mice. Glycolytic and gluconeogenic enzyme activities were measured in fed and overnight fasted 19- to 20-wk-old NZO and control New Zealand chocolate mice. The NZO mice were twice as heavy as the NZC mice. The activity of the glycolytic enzymes glucokinase and pyruvate kinase was higher, whereas that of the gluconeogenic enzymes PEPCK and glucose-6-phosphatase was lower in fed and fasted NZO mice. These enzyme changes are consistent with a normal response to the hyperinsulinemia in NZO mice. In contrast, the activity of the third regulated gluconeogenic enzyme, fructose-1,6-bisphosphatase, was similar in fed and fasted NZO and NZC mice despite the higher insulin and glucose levels in the NZO mouse. This enzyme is primarily regulated by the powerful inhibitor fructose-2,6-bisphosphate. The levels of this metabolite were measured and found to be increased in both the fed and fasted states in the NZO mouse, suggesting that the activity of the bifunctional enzyme that regulates the level of inhibitor (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) is normally regulated in the NZO mouse. We conclude that most insulin-responsive gluconeogenic and glycolytic enzymes are normally regulated in the NZO mouse, but an abnormality in the regulation of fructose-1,6-bisphosphatase may contribute to the increase hepatic glucose production in these mice.
Testicular hamartomas in Cowden disease

We report a case of testicular hamartomas in association with Cowden disease. Clinical examination of the patient, a 39‐year‐old man, revealed a palpable mass in the right side of the scrotum. Sonographic examination showed that the mass was either a spermatocele or an epididymal cyst and that multiple hyperechoic lesions were present in both testes. On subsequent MRI, the appearance of these lesions was consistent with that of fat‐containing hamartomas. Testicular biopsy was not performed, but follow‐up serial sonographic examination was recommended. To our knowledge, this report is the first to describe testicular hamartomas as a probable manifestation of Cowden disease. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:481–483, 2003
A Case-Control Study to Add Volumetric or Clinical Mammographic Density into the Tyrer-Cuzick Breast Cancer Risk Model

Abstract Background Accurate breast cancer risk assessment for women attending routine screening is needed to guide screening and preventive interventions. We evaluated the accuracy of risk predictions from both visual and volumetric mammographic density combined with the Tyrer-Cuzick breast cancer risk model. Methods A case-control study (474 patient participants and 2243 healthy control participants) of women aged 40–79 years was performed using self-reported classical risk factors. Breast density was measured by using automated volumetric software and Breast Imaging and Reporting Data System (BI-RADS) density categories. Odds ratios (95% CI) were estimated by using logistic regression, adjusted for age, demographic factors, and 10-year risk from the Tyrer-Cuzick model, for a change from the 25th to 75th percentile of the adjusted percent density distribution in control participants (IQ-OR). Results After adjustment for classical risk factors in the Tyrer-Cuzick model, age, and body mass index (BMI), BI-RADS density had an IQ-OR of 1.55 (95% CI = 1.33 to 1.80) compared with 1.40 (95% CI = 1.21 to 1.60) for volumetric percent density. Fibroglandular volume (IQ-OR = 1.28, 95% CI = 1.12 to 1.47) was a weaker predictor than was BI-RADS density (Pdiff = 0.014) or volumetric percent density (Pdiff = 0.065). In this setting, 4.8% of women were at high risk (8% + 10-year risk), using the Tyrer-Cuzick model without density, and 7.1% (BI-RADS) compared with 6.8% (volumetric) when combined with density. Conclusion The addition of volumetric and visual mammographic density measures to classical risk factors improves risk stratification. A combined risk could be used to guide precision medicine, through risk-adapted screening and prevention strategies.
Ensembles of Multi-Scale VGG Acoustic Models

We present our work on constructing multi-scale deep convolutional neural networks for automatic speech recognition. Several VGG nets have been trained that differ solely in the kernel size of the convolutional layers. The general idea is that receptive fields of varying sizes match structures of different scales, thus supporting more robust recognition when combined appropriately. We construct a large multi-scale system by means of system combination. We use ROVER and the fusion of posterior predictions as examples of late combination, and knowledge distillation using soft labels from a model ensemble as a way of early combination. In this work, distillation is approached from the perspective of knowledge transfer pretraining, which is followed by a fine-tuning on the original hard labels. Our results show that it is possible to bundle the individual recognition strengths of the VGGs in a much simpler CNN architecture that yields equal performance with the best late combination.
Deep Transfer Learning for Few-Shot SAR Image Classification

The reemergence of Deep Neural Networks (DNNs) has lead to high-performance supervised learning algorithms for the Electro-Optical (EO) domain classification and detection problems. This success is because generating huge labeled datasets has become possible using modern crowdsourcing labeling platforms such as Amazon’s Mechanical Turk that recruit ordinary people to label data. Unlike the EO domain, labeling the Synthetic Aperture Radar (SAR) domain data can be much more challenging, and for various reasons, using crowdsourcing platforms is not feasible for labeling the SAR domain data. As a result, training deep networks using supervised learning is more challenging in the SAR domain. In the paper, we present a new framework to train a deep neural network for classifying Synthetic Aperture Radar (SAR) images by eliminating the need for a huge labeled dataset. Our idea is based on transferring knowledge from a related EO domain problem, where labeled data are easy to obtain. We transfer knowledge from the EO domain through learning a shared invariant cross-domain embedding space that is also discriminative for classification. To this end, we train two deep encoders that are coupled through their last year to map data points from the EO and the SAR domains to the shared embedding space such that the distance between the distributions of the two domains is minimized in the latent embedding space. We use the Sliced Wasserstein Distance (SWD) to measure and minimize the distance between these two distributions and use a limited number of SAR label data points to match the distributions class-conditionally. As a result of this training procedure, a classifier trained from the embedding space to the label space using mostly the EO data would generalize well on the SAR domain. We provide a theoretical analysis to demonstrate why our approach is effective and validate our algorithm on the problem of ship classification in the SAR domain by comparing against several other competing learning approaches.
Comparison of ceftibuten transport across Caco‐2 cells and rat jejunum mounted on modified ussing chambers

Ceftibuten uptake into Caco‐2 cells and intestinal brush border membrane vesicles is mediated by the dipeptide transport system (PEPT1). The apical to basolateral transport characteristics of ceftibuten across Caco‐2 cells and rat jejunum mounted on a modified Ussing chamber was examined. Mannitol was used as a paracellular marker along with trans‐epithelial electrical resistance (TEER) for monitoring tight junction permeability. Transport across Caco‐2 cells and rat jejunum mounted on a modified Ussing chamber was linear across the concentration range 0.25–10 mm. The net flux of mannitol and ceftibuten was higher across rat jejunum compared with Caco‐2 cells. At a donor concentration of 0.25 mm, ceftibuten transport across Caco‐2 cells was found to be pH dependent. Glycyl proline, a dipeptide, and 2,4‐ dinitrophenol, an energy poison, caused a reduction in the permeability of 0.25 mm ceftibuten across Caco‐2 cells. Benzoic acid and adipic acid also inhibited transcellular transport of ceftibuten. At a donor concentration of 0.25 mm, passive paracellular transport accounts for about 60% and the active carrier mediated mechanism accounts for about 40% of ceftibuten transport across Caco‐2 cells. None of the inhibitors however, had a significant effect on ceftibuten transport across rat jejunum mounted on a modified Ussing chamber at a donor concentration of 0.25 mm. In the concentration range 0.25–10 mm, ceftibuten is predominantly transported by paracellular mechanisms across rat jejunum and a mixture of active and passive transport across Caco‐2 cells. Copyright © 2003 John Wiley & Sons, Ltd.
Guaranteed cost control for uncertain discrete-time switched systems with time-delay

This paper deals with the guaranteed cost control problem for a class of uncertain linear discrete-time switched systems with time-delay under arbitrary switching laws. The purpose is to design a state feedback control law such that the closed-loop system is asymptotically stable and the closed-loop cost function value is not more than a specified upper bound for all admissible uncertainties. A sufficient condition on the existence of guaranteed cost controllers is derived based on Lyapunov theory together with linear matrix inequality (LMI) approach. Furthermore, a convex optimization problem with LMIs constraints is formulated to select the suboptimal guaranteed cost controller. A numerical example demonstrates the validity of the proposed design approach.
Acute graft‐versus‐host disease after liver transplant: Novel use of etanercept and the role of tumor necrosis factor α inhibitors

Acute graft‐versus‐host disease following orthotopic liver transplantation is a rare but feared complication arising in 1% to 2% of cases with a dismal prognosis. It most often presents as fever, rash, and diarrhea with or without pancytopenia. Patients die from complications of marrow failure such as sepsis or bleeding. Because of its low incidence, there is no clear treatment protocol for this complication. Both increasing and withdrawing immunosuppression have been attempted with variable success. Although anti–tumor necrosis factor α therapy has been widely used for the treatment of steroid‐resistant acute graft‐versus‐host disease in the hematopoietic stem cell transplant setting, there previously have been no reported cases of its use in liver transplantation. The aim of this report is to review a case of acute graft‐versus‐host disease and the use of etanercept to manage this complication. Etanercept has never previously been used in liver transplantation complicated by acute graft‐versus‐host disease. In the hematology literature, the success of its use is offset by significant rates of serious infectious (especially fungal) complications. However, preliminary results are encouraging and offer insight into its use as a potentially viable therapeutic option. We report the first successful use of etanercept in liver transplantation–associated graft‐versus‐host disease, albeit complicated by invasive aspergillosis, and recommend concurrent antifungal prophylaxis when the drug is used in this setting. Liver Transpl 15:421–426, 2009. © 2009 AASLD.