Miracle-dz/UniFAR-FTUs huggingface dataset:
Uptake andAntitumoral Effects of Iodine and 6-Iodolactone inDifferentiatedandUndifferentiated HumanProstateCancerCell Lines

BACKGROUND. Evidence indicates that iodine per se could be implicated in the physiology of several organs that can internalize it. In thyroid and breast cancer, iodine treatments inhibit cell proliferation and induce apoptosis through a direct (mitochondria) and/or indirect effect (iodolipid generation). Here, we determined the uptake of iodide (I ) and iodine (I2), as well as the antiproliferative and apoptotic effects of 6-iodolactone (6-IL) and both forms of iodine in human prostate cells lines. METHODS. Non-cancerous (RWPE-1) and cancerous (LNCaP, DU-145) cells, as well as nude mice xenotransplanted with DU-145 cells were used as cancer models. Iodine uptake was analyzed with radioactive tracers, transporter expression by qRT-PCR, cell proliferation by blue trypan, apoptosis by enzyme immunoassay or fluorescence, BAX and BCL-2 by western-blot, and caspsase 3 by enzymatic assay. RESULTS. All three cell lines take up both forms of iodine. In RWPE-1 cells, I uptake depends on the Naþ/I symporter (NIS), whereas it was independent of NIS in LNCaP and DU-145 cells. Antiproliferative effects of iodine and 6-IL were dose and time dependent; RWPE-1 was most sensitive to I and 6-IL, whereas LNCaP was more sensitive to I2. In the three cell lines both forms of iodine activated the intrinsic apoptotic pathway (increasing the BAX/BCL-2 index and caspases). Iodine supplementation impaired growth of the DU-145 tumor in nude mice. CONCLUSION. Normal and cancerous prostate cells can take up iodine, and depending on the chemical form, it exerts antiproliferative and apoptotic effects both in vitro and in vivo. Prostate 73: 31–41, 2013. # 2012 Wiley Periodicals, Inc.
TGF-beta1 stimulation of fibronectin transcription in cultured human lung fibroblasts requires active geranylgeranyl transferase I, phosphatidylcholine-specific phospholipase C, protein kinase C-delta, and p38, but not erk1/erk2.

The cytokine transforming growth factor-beta (TGF-beta) has multiple effects on a variety of cell types, modulating cell growth and differentiation as well as extracellular matrix deposition and degradation. In the present work, we demonstrate that TGF-beta1 produces a fourfold increase in transcription of the fibronectin gene in cultured human fetal lung fibroblasts with only a small increase in mRNA stability resulting in a significant increase in fibronectin mRNA steady state level. A corresponding increase in production of fibronectin protein accompanied the increase in mRNA. Through the use of specific inhibitors, we demonstrate that geranylgeranylated, but not farnesylated or acylated protein(s), protein kinase C-delta, phosphatidylcholine-specific phospholipse C, tyrosine kinase activity, and stress-activated protein kinase p38 are required for this TGF-beta1 effect. Trimeric G proteins and mitogen-activated protein kinases erk1 and erk2 do not appear to be involved. While these results emphasize the complexities involved in the control of extracellular matrix synthesis by TGF-beta, they also identify reaction sites that may be amenable to pharmacologic modulation. Such modulation could be of great advantage in the treatment of a wide variety of undesirable fibrotic reactions.
ALGINATE LYASE: review of major sources and enzyme characteristics, structure-function analysis, biological roles, and applications.

Alginate lyases, characterized as either mannuronate (EC 4.2.2.3) or guluronate lyases (EC 4.2.2.11), catalyze the degradation of alginate, a complex copolymer of alpha-L-guluronate and its C5 epimer beta-D-mannuronate. Lyases have been isolated from a wide range of organisms, including algae, marine invertebrates, and marine and terrestrial microorganisms. This review catalogs the major characteristics of these lyases, the methods for analyzing these enzymes, as well as their biological roles. Analysis of primary sequence data identifies some markedly conserved motifs that should help elucidate functional domains. Information about the three-dimensional structure of a mannuronate lyase from Sphingomonas sp. , combined with various mutagenesis studies, has identified residues that are important for catalytic activity in several lyases. Characterization of alginate lyases will enhance and expand the use of these enzymes to engineer novel alginate polymers for applications in various industrial, agricultural, and medical fields. In this review, we explore both past and present applications of this important enzyme and discuss its future prospects.
Reexamining Free Flap Breast Reconstruction in the Community and University Setting: Is There a Difference?

BackgroundThis study aimed to compare free flap breast reconstruction outcomes in community and university settings to determine whether the latter is necessary for successful performance of this complex procedure. MethodsFree tissue transfer procedures for breast reconstruction from 1 university and 1 community hospital performed between 2005 and 2011 were included. Procedures were performed by the same 2 surgeons at both institutions. Demographics and outcome measures were evaluated. ResultsOf the 1293 free tissue breast reconstructions performed, 99 (7.7%) were performed in a community hospital and 1194 (92.3%) were performed in a university center. No differences were noted in demographics, comorbidities, or type of free flap reconstruction. However, a number of perioperative characteristics differed. In the community setting, operative time was less (7.3 vs 8.3 hours, P < 0.0001), estimated blood loss was higher (330 vs 248 mL, P < 0.0001), and blood transfusions were more prevalent (24.6% vs 8.3%, P < 0.0001). Furthermore, no significant differences were noted in overall postoperative complications, although a higher rate of abdominal wound infections was noted in the community setting (7.2% vs 2.6%, P = 0.03). The mean number of hospital days was similar between the community and the university (should include value P = 0.44). ConclusionsAlthough slight differences were noted in a number of perioperative variables and wound complications, we conclude that the key to a successful free tissue transfer reconstruction is in the expertise of the surgeon and not the setting in which it is performed. Despite its complexity, free flap breast reconstruction can be safely and successfully performed in the community setting.
FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: Insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States

Purpose: Fragile X syndrome is caused by expansion and methylation of a CGG tract in the 5′ untranslated region of the FMR1 gene. The estimated frequency of expanded alleles (≥55 repeats) in the United States is 1:257–1:382, but these estimates were not calculated from unbiased populations. We sought to determine the frequency of fragile X syndrome premutation (55–200 repeats) and full mutation (>200 repeats) alleles in nonselected, unbiased populations undergoing routine carrier screening for other diseases.Methods: A previously validated laboratory-developed test using triplet-primed polymerase chain reaction was used to detect premutation and full mutation alleles in an unselected series of 11,759 consecutive cystic fibrosis carrier screening samples and 2011 samples submitted for screening for genetic diseases prevalent among the Ashkenazi Jewish population.Results: Premutations were identified in 48 cystic fibrosis screening samples (1:245) and 15 samples (1:134) from the Ashkenazi Jewish population. Adjusted for the ethnic mix of the US population and self-reported ethnicity in our screening population, the estimated female premutation carrier frequency in the United States was 1:178. The calculated frequency of full mutation alleles was 1:3335 overall, and the calculated premutation frequency in males was 1:400. Based on frequency of larger, ≥70 repeat alleles, and reported penetrance, the calculated fragile X-associated tremor and ataxia syndrome, and fragile X-associated primary ovarian insufficiency frequencies is 1:4848 and 1:3560, respectively.Conclusion: Our calculated fragile X syndrome carrier rate is higher than previous estimates for the US population and warrants further consideration of population-based carrier screening.
Predicting conditional probability distributions: a connectionist approach

Most traditional prediction techniques deliver a single point, usually the mean of a probability distribution. For multimodal processes, instead of predicting the mean, it is important to predict the full distribution. This article presents a new connectionist method to predict the conditional probability distribution in response to an input. The main idea is to transform the problem from a regression problem to a classification problem. The conditional probability distribution network can perform both direct predictions and iterated predictions, the latter task being specific for time series problems. We compare this new method to fuzzy logic and discuss important differences, and also demonstrate the architecture on two time series. The first is the benchmark laser series used in the Santa Fe competition, a deterministic chaotic system. The second is a time series from a Markov process which exhibits structure on two time scales. The network produces multimodal predictions for this series. We compare the predictions of the network with a nearest-neighbor predictor and find that the conditional probability network is more than twice as likely a model.
Title Analytical techniques for the determination of biologically active quinonesin biological and environmental samples

Right © 2013 Published by Elsevier B.V. All rights reserved. ; NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Pharmaceutical and Biomedical Analysis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Pharmaceutical and Biomedical Analysis, 87(2014) NAOSITE: Nagasaki University's Academic Output SITE
Bcr1 plays a central role in the regulation of opaque cell filamentation in Candida albicans

The human fungal pathogen Candida albicans has at least two types of morphological transitions: white to opaque cell transitions and yeast to hyphal transitions. Opaque cells have historically not been known to undergo filamentation under standard filament‐inducing conditions. Here we find that Bcr1 and its downstream regulators Cup9, Nrg1 and Czf1 and the cAMP‐signalling pathway control opaque cell filamentation in C. albicans. We have shown that deletion of BCR1, CUP9, NRG1 and CZF1 results in opaque cell filamentation under standard culture conditions. Disruption of BCR1 in white cells has no obvious effect on hyphal growth, suggesting that Bcr1 is an opaque‐specific regulator of filamentation under the conditions tested. Moreover, inactivation of the cAMP‐signalling pathway or disruption of its downstream transcriptional regulators, FLO8 and EFG1, strikingly attenuates filamentation in opaque cells of the bcr1/bcr1 mutant. Deletion of HGC1, a downstream gene of the cAMP‐signalling pathway encoding G1 cyclin‐related protein, completely blocks opaque cell filamentation induced by inactivation of BCR1. These results demonstrate that Bcr1 regulated opaque cell filamentation is dependent on the cAMP‐signalling pathway. This study establishes a link between the white‐opaque switch and the yeast‐filamentous growth transition in C. albicans.
Effects of Stroop color-word conflict test on the autonomic nervous system responses.

The Stroop color-word test (CWT) is a mental stress test involving sensory rejection and has been used as a model of the defense reaction in humans. The present study was designed to investigate effects of CWT on resting cardiac autonomic nervous system activity evaluated by analyses of heart rate (HR) variability (HRV). Eight healthy subjects performed 21 min of CWT after 14 min of resting control followed by 14 min of recovery (RCV). Beat-to-beat R-R intervals (RRI, i.e., HRV), systolic blood pressure (SBP), and instantaneous lung volume were continuously monitored throughout these periods. Steady-state HRV data (10-12 min) for resting control and recovery (12 min) and for 1-11 min (CWT1) and 11-21 min (CWT2) of CWT were analyzed by coarse-graining spectral analysis to break down their total power into harmonic and nonharmonic (fractal) components. The harmonic component was further divided into low (0.0-0.15 Hz, LF)- and high (>0.15 Hz, HF)-frequency components. Cardiac sympathetic (SNS) and parasympathetic (PNS) nervous system activity indicators were evaluated as LF/HF and HF/TP, respectively [LF, HF, and total spectral power (TP) of HRV]. The fractal component had the spectrum of 1/f(beta), and the spectral exponent beta was calculated. RRI decreased and SBP, plasma norepinephrine, and epinephrine concentrations increased significantly (P < 0.05) in response to CWT (CWT1 and CWT2). PNS and SNS indicators did not show any significant (P > 0.05) difference between resting controls and CWT. Whereas the percentage of fractal components in total HRV remained unchanged, beta decreased significantly (P < 0.05) in response to CWT. Transfer magnitudes from SBP to RRI, calculated by cross-spectral analysis, decreased at CWT2. The transfer magnitudes from instantaneous lung volume to RRI were also decreased significantly (P < 0.05) by CWT. It was concluded that although CWT did not affect the SNS indicator of HRV, despite altered HR and vasomotor responses, tonic sympathetic nervous system influence was observed for norepinephrine and epinephrine. In addition, reflex blood pressure (CWT2) and respiratory modulation of HR (CWT1 and CWT2) decreased during CWT. Mental stress altered the fractal nature of HRV (as judged by decreased beta), but mechanism(s) responsible for this change remained unknown.
FEA design and computation system for springs

Nowadays, new kinds of springs have been applied. Their design is adapted specifically to the construction environment as well as for the fulfilment of several tasks (multifunction springs). For their calculation, standard methods of analysis fail. The Finite Element Analysis (FEA) offers itself as a computation possibility. But, in most cases, design engineers cannot meet the demands connected with the FEA application on account of their tasks and position in the design process as well as their training. A coupled CAD/FEA system is adapted to the specifications of the design of springs and spring assemblies and facilitates the application of the FEA essentially by a design engineer. The SPRINGPROCESSOR, as the heart of the described system, is completely realised. It uses in an exemplary way the programming possibilities of the FEA system ANSYS. Starting with the problem arising in the application of the Finite Element Analysis in spring engineering, solution ideas and the basic architecture of the CAD/FEA system are described and, by means of selected examples, the basic procedure and the capability of the program system is illustrated.
An Interference Coordination Scheme for Device-to-Device Multicast in Cellular Networks

In this paper a multicast concept for Device-to-Device (D2D) communication underlaying a cellular infrastructure has been investigated. To improve system throughput and increase resource utilization, a novel interference coordination scheme is proposed. The proposed scheme includes two steps. First, in order to mitigate the interference from D2D transmission to cellular communication, we propose an efficient power control scheme to obtain an upper bound of D2D transmitter power. Next, based on the upper bound, two resource block (RB) allocation rules aiming to control the interference from cellular networks (CNs) to receivers in D2D multicast group are proposed. Simulation results show that by applying the proposed scheme, the performance of the hybrid system can be significantly improved compared to the conventional ways.
In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K-AKT Signaling at Endosomes.

UNLABELLED The phosphatases PTEN and INPP4B have been proposed to act as tumor suppressors by antagonizing PI3K-AKT signaling and are frequently dysregulated in human cancer. Although PTEN has been extensively studied, little is known about the underlying mechanisms by which INPP4B exerts its tumor-suppressive function and its role in tumorigenesis in vivo. Here, we show that a partial or complete loss of Inpp4b morphs benign thyroid adenoma lesions in Pten heterozygous mice into lethal and metastatic follicular-like thyroid cancer (FTC). Importantly, analyses of human thyroid cancer cell lines and specimens reveal INPP4B downregulation in FTC. Mechanistically, we find that INPP4B, but not PTEN, is enriched in the early endosomes of thyroid cancer cells, where it selectively inhibits AKT2 activation and in turn tumor proliferation and anchorage-independent growth. We therefore identify INPP4B as a novel tumor suppressor in FTC oncogenesis and metastasis through localized regulation of the PI3K-AKT pathway at the endosomes. SIGNIFICANCE Although both PTEN and INPP4B can inhibit PI3K-AKT signaling through their lipid phosphatase activities, here we demonstrate lack of an epistatic relationship between the two tumor suppressors. Instead, the qualitative regulation of PI3K-AKT2 signaling by INPP4B provides a mechanism for their cooperation in suppressing thyroid tumorigenesis and metastasis.
The state-based testing of object-oriented programs

State-based testing, a technique used for the validation of object-oriented programs with emphasis on the interaction between the features and the object's state, is described. Because of the nature of the technique, the random order in which features can be invoked is taken into account. The technique is complementary to other functional and structural approaches to validation. A suite of tools to support the state-based testing of object-oriented programs is also outlined. The adaptation of traditional validation techniques to the object-oriented programming model is also discussed. <<ETX>>
Going Polymorphic - TH1 Reasoning for Leo-III

While interactive proof assistants for higher-order logic (HOL) commonly admit reasoning within rich type systems, current theorem provers for HOL are mainly based on simply typed λ-calculi and therefore do not allow such flexibility. In this paper, we present modifications to the higher-order automated theorem prover Leo-III for turning it into a reasoning system for rank-1 polymorphic HOL. To that end, a polymorphic version of HOL and a suitable paramodulation-based calculus are sketched. The implementation is evaluated using a set of polymorphic TPTP THF problems.
XPLOITING MODEL CAPACITY BY CONSTRAINING WITHIN-BATCH FEATURES TO BE ORTHOGONAL

Deep networks have been shown to greatly benefit from large model capacity when trained using various recent deep learning techniques. But at the same time, features in such large capacity networks have a potential to be redundant. In this work, we propose a new regularization method to exploit the given network capacity effectively. By minimizing the redundancy among in-layer filters and the correlation between in-batch features at the same time, we are able to achieve better performance with the same network architecture. Experiments with CIFAR-10/100 show that simultaneously constraining both the in-layer filters to be orthonormal and the in-batch features to be orthogonal is beneficial in efficiently utilizing the model capacity.
How to teach Slovak TTS to speak (Serviko) Romani

The paper presents the first step of our attempt to enable speech driven information technologies in Romani. A short overview is given of Romani orthography, phonetic inventory, pronunciation rules, and prosody. Differences between Slovak and Romani language systems are pointed out and the resulting knowledge is used to design parts of the Romani diphone synthesizer derived from the corresponding parts of our Slovak diphone synthesizer Kempelen 1.2 with male voice Milan and Kempelen 1.4 with female voice Anna. The first listening experiments indicate that the proposed procedure porting an existing Slovak speech synthesizer to Romani is effective and represents for us the fastest and cheapest way of creating a well understandable basic level synthesizer in Romani. This synthesizer can be immediately used in the design of speech driven information systems in Romani. But the main achievement of this work is that we have acquired skills in processing new language, we have found its main peculiarities, and have prepared the basic speech processing background needed for further development of much more comprehensive speech technology applications like paedagogical tools and information systems using unit-selection synthesis and automatic speech recognition in Romani.
Synchronization of Indian Weaver Bird Circadian Rhythms to Food and Light Zeitgebers: Role of Pineal

This study investigates the relative strengths of food and light zeitgebers in synchronization of circadian rhythms of Indian weaver birds and the role of the pineal gland in food-induced synchronization of the circadian activity rhythms. Two experiments were performed. In the first experiment, six birds were concurrently exposed for 10 days to PA 12/12 (12 h food present: 12 h food absent) and LD 12/12 (12 h light: 12 h dark). Then, the PA 12/12 cycle was reversed: food was present during the dark period of the LD 12/12 cycle. After 15 days, birds were released into constant dim light (LLdim). During exposure to overlapping light and food availability periods, birds were active only during the daytime. When light and food availability periods were presented in antiphase, two of six birds became night active. However, with the removal of the light zeitgeber (i.e., under LLdim), all birds were synchronized with reversed PA 12/12; hence, they were active during the subjective night (i.e., the period corresponding to darkness [ZT12-0] of the preceding LD 12/12). The second experiment examined whether the pineal contributed to the food-induced synchronization. After two weeks of concurrent PA 12/12 and LD 12/12 exposure, six birds were released into LLdim for 2.5 weeks. Under LLdim, five of six birds were synchronized to PA 12/12 with the circadian period (tau, τ) = 24 h. The LD 12/12 was restored, and after seven days, birds were pinealectomized (pinx). After 2.5 weeks, pinx birds were again released into LLdim for 2.5 weeks. Under LLdim, pinx birds did not become arrhythmic; instead, they appeared synchronized to PA 12/12 with τ = 24 h (n = 4) or ∼24 h (n = 2). We conclude that both food and light act as zeitgebers, although light appears to be the relatively stronger cue when the two are present together, as in the natural environment. We also found that the pineal is not necessary for food-induced synchronization. The findings suggest that food cycles could act as the synchronizer of circadian rhythmicity in biological functions in individuals held in an aperiodic environment.