pinecone/core-2020-05-10-deduplication huggingface dataset:
Toward a quantitative understanding of the Wnt/beta-catenin pathway through simulation and experiment

Wnt signaling regulates cell survival, proliferation, and differentiation throughout development and is aberrantly regulated in cancer. The pathway is activated when Wnt ligands bind to specific receptors on the cell surface, resulting in the stabilization and nuclear accumulation of the transcriptional co‐activator β‐catenin. Mathematical and computational models have been used to study the spatial and temporal regulation of the Wnt/β‐catenin pathway and to investigate the functional impact of mutations in key components. Such models range in complexity, from time‐dependent, ordinary differential equations that describe the biochemical interactions between key pathway components within a single cell, to complex, multiscale models that incorporate the role of the Wnt/β‐catenin pathway target genes in tissue homeostasis and carcinogenesis. This review aims to summarize recent progress in mathematical modeling of the Wnt pathway and to highlight new biological results that could form the basis for future theoretical investigations designed to increase the utility of theoretical models of Wnt signaling in the biomedical arena
Tuneable resolution as a systems biology approach for multi-scale, multi-compartment computational models

The use of multi-scale mathematical and computational models to study complex biological processes is becoming increasingly productive. Multi-scale models span a range of spatial and/or temporal scales and can encompass multi-compartment (e.g., multi-organ) models. Modeling advances are enabling virtual experiments to explore and answer questions that are problematic to address in the wet-lab. Wet-lab experimental technologies now allow scientists to observe, measure, record, and analyze experiments focusing on different system aspects at a variety of biological scales. We need the technical ability to mirror that same flexibility in virtual experiments using multi-scale models. Here we present a new approach, tuneable resolution, which can begin providing that flexibility. Tuneable resolution involves fine- or coarse-graining existing multi-scale models at the user's discretion, allowing adjustment of the level of resolution specific to a question, an experiment, or a scale of interest. Tuneable resolution expands options for revising and validating mechanistic multi-scale models, can extend the longevity of multi-scale models, and may increase computational efficiency. The tuneable resolution approach can be applied to many model types, including differential equation, agent-based, and hybrid models. We demonstrate our tuneable resolution ideas with examples relevant to infectious disease modeling, illustrating key principles at work. WIREs Syst Biol Med 2014, 6:225–245. doi:10.1002/wsbm.1270 How to cite this article: WIREs Syst Biol Med 2014, 6:289–309. doi:10.1002/wsbm.127
Bringing computational models of bone regeneration to the clinic.

Although the field of bone regeneration has experienced great advancements in the last decades, integrating all the relevant, patient-specific information into a personalized diagnosis and optimal treatment remains a challenging task due to the large number of variables that affect bone regeneration. Computational models have the potential to cope with this complexity and to improve the fundamental understanding of the bone regeneration processes as well as to predict and optimize the patient-specific treatment strategies. However, the current use of computational models in daily orthopedic practice is very limited or inexistent. We have identified three key hurdles that limit the translation of computational models of bone regeneration from bench to bed side. First, there exists a clear mismatch between the scope of the existing and the clinically required models. Second, most computational models are confronted with limited quantitative information of insufficient quality thereby hampering the determination of patient-specific parameter values. Third, current computational models are only corroborated with animal models, whereas a thorough (retrospective and prospective) assessment of the computational model will be crucial to convince the health care providers of the capabilities thereof. These challenges must be addressed so that computational models of bone regeneration can reach their true potential, resulting in the advancement of individualized care and reduction of the associated health care costs. WIREs Syst Biol Med 2015, 7:183-194. doi: 10.1002/wsbm.1299 For further resources related to this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article.Peer reviewe
In silico bone mechanobiology: modeling a multifaceted biological system

Mechanobiology, the study of the influence of mechanical loads on biological processes through signaling to cells, is fundamental to the inherent ability of bone tissue to adapt its structure in response to mechanical stimulation. The immense contribution of computational modeling to the nascent field of bone mechanobiology is indisputable, having aided in the interpretation of experimental findings and identified new avenues of inquiry. Indeed, advances in computational modeling have spurred the development of this field, shedding new light on problems ranging from the mechanical response to loading by individual cells to tissue differentiation during events such as fracture healing. To date, in silico bone mechanobiology has generally taken a reductive approach in attempting to answer discrete biological research questions, with research in the field broadly separated into two streams: (1) mechanoregulation algorithms for predicting mechanobiological changes to bone tissue and (2) models investigating cell mechanobiology. Future models will likely take advantage of advances in computational power and techniques, allowing multiscale and multiphysics modeling to tie the many separate but related biological responses to loading together as part of a larger systems biology approach to shed further light on bone mechanobiology. Finally, although the ever-increasing complexity of computational mechanobiology models will inevitably move the field toward patient-specific models in the clinic, the determination of the context in which they can be used safely for clinical purpose will still require an extensive combination of computational and experimental techniques applied to in vitro and in vivo applications
Si PIN X-ray photon counter

A Si PIN detector for visible light detection, instead of a Geiger-Müller tube, is applied to X-ray photon counting. We counted radiation from a checking source of a Geiger-Müller counter with a Si PIN counter and with a Geiger-Müller counter. White X-ray of energy up to 20 keV emitted from a pyroelectric X-ray emitter was also counted, and the Si PIN X-ray counter showed a similar curve of count rate versus source distance in both measurements. Pulse counting was performed by spectroscopy circuits. An audio digitizer with computer software for signal processing was also used to simplify the photon counter. A plot of count rate versus time was obtained with this setup. With simple pulse counting circuits, Si PIN X-ray counters have advantages such as compact structure, low cost and easy application
EDXRF with an audio digitizer

We utilized an audio digitizer in energy-dispersive X-ray fluorescence (EDXRF) with a silicon drift detector and achieved a full width at half maximum (FWHM) of 178 eV at Mn Kα (92-µs peaking time). To confirm the ability of EDXRF with an audio digitizer, we also examined energy versus channel number linearity and output count rate. We applied it to EDXRF analysis of (ZnCd)S : Ag and showed a proper energy versus channel number linearity from 5.9 keV (Mn Kα) to 26.1 keV (Cd Kβ). And, the maximum output count rate of more than 10 kcps was obtained with 23-µs peaking time (296-eV FWHM)
PXRF and multivariate statistics analysis of pre-colonial pottery from northeast of Brazil

Portable system of energy dispersive X-ray fluorescence was used to determine the elemental composition of 68 pottery fragments from Sambaqui do Bacanga, an archeological site in Sao Luis, Maranhao, Brazil. This site was occupied from 6600 BP until 900 BP. By determining the element chemical composition of those fragments, it was possible to verify the existence of engobe in 43 pottery fragments. Obtained from two-dimensional graphs and hierarchical cluster analysis performed in fragments of stratigraphies from surface and 113-cm level, and 10 to 20, 132 and 144-cm level, it was possible to group these fragments in five distinct groups, according to their stratigraphies. The results of data grouping (two-dimensional graphics) are in agreement with hierarchical cluster analysis by Ward method. Copyright (C) 2011 John Wiley & Sons, Ltd
Forensic analysis of arsenic poisoning in Japan by synchrotron radiation X-ray fluorescence

Synchrotron radiation X-ray fluorescence (SR-XRF) analysis reports of a poisoning case by arsenic, 25 July 1998, Japan, for forensic investigation purposes are reviewed. In these forensic analyses, SPring-8 and KEK-PF beamlines were used for minor element (Sn, Sb, Mo, Bi, Ba) analysis in the arsenic pesticide specimens, sampled at the crime scene as well as the neighborhood of the suspect. For this case, two kinds of documents were submitted to court: one was a qualitative analysis and said to be a ‘pattern recognition’ by Prof. Nakai, and the other was, by Profs Taniguchi and Hayakawa, a quantitative analysis after background subtraction, normalized by the sample thickness, where calibration curves were made with reference to the inductively coupled plasma atomic emission spectrometry (ICP-AES) analysis for reference samples. The final decision of the court was a death sentence based on the qualitative ‘pattern recognition’. The present review concludes that the quantitative analysis by Profs Taniguchi and Hayakawa was scientifically more important than the ‘pattern recognition’ qualitative analysis, because the Taniguchi-Hayakawa report used novel but reliable data processing methods. The Sn, Sb, and Mo Kα intensities were normalized with respect to the As (major element) Kα (10.5 keV) intensity as a thick target, whereas the Bi and Ba Kα intensities were normalized by the Rayleigh scattering (for 116 keV incident beam) as a thin target. The Taniguchi-Hayakawa report was the first quantitative report in high-energy SR-XRF analysis. The most important conclusion in the present review is that the ICP-AES was more reliable over these SR-XRF analyses, because even the beamline selection was not possible without the knowledge of the impurity elements obtained by the ICP-AES. Five elements (Se, Sn, Sb, Pb, and Bi) were used in ICP-AES for identification compared with only three elements (Sn, Sb, and Bi) in SR-XRF. High blank intensity resulted from using Pb for X-ray collimator in the beamline. Overlapping of the analytical lines of minor Se and major As prevented the use of Se for identification. Recent analysis of Fe, Zn, Mo, and Ba in Nakai's raw spectra measured in 1998 reveals the arsenic stored in the kitchen of the condemned criminal in the death row was significantly different from that of the paper cup used for poisoning
Identification of local and allochthonous flint artefacts from the Middle Paleolithic site Abrigo de la Quebrada (Chelva, Valencia, Spain) by macroscopic and physicochemical methods

Flint is a lithic material that can be worked to obtain sharp blades with conchoidal fractures characteristic of lithic tools as scrapers, hand axes and arrowheads. These artefacts represent the majority of the lithic material from the Palaeolithic sites worldwide, and it continued to be used during subsequent periods to manufacture some of the earliest tools used by man. One of the questions that archaeologists are keen to answer in relation to flint use and characterization is sourcing. Answering this question is important to reconstruct interaction networks of prehistoric cultures. Over the past years, a great variety of analytical methods have been applied to identify the sources of flint artefacts found in different archaeological contexts.[1<br>8] The objective of these studies is to determine the chemical composition of geological and archaeological flint samples and to obtain element correspondences to establish the probable geological source of origin for archaeological artefacts
Occurrence of tin in disposable baby diapers

Concentrations of tin were measured in six different brands of disposable baby diapers by using radioisotope (americium) excited energy dispersive x-ray fluorescence. Top sheet and adhesive tape system were measured separately. The concentrations found in top sheet and tape system were <1.5 to 23.1 mg/kg and <1.5 to 22.4 mg/kg, respectively. Almost all diapers contained tin in the adhesive tape system (four of five) and two of six samples contained tin in top sheet. Tin found in diapers may be an organotin substance: tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT) and/or dioctyltin (DOT), which are widely used in industrial processes as catalysts or as PVC heat stabilizers. Organotin substances have toxic effects which include neurotoxicity, reproductive and developmental toxicity, immunotoxicity, and endocrine disruption. The measured concentrations were less than EU regulatory levels of 0.1% by weight of tin prescribed by REACH Annex XVII No 20. However, the same regulation completely bans the use of organotin substances as biocides in antifouling paints. While effects of TBT on marine organisms from antifouling paints are well known, the effects of organotin compounds in childcare products and other commercial articles receive much less attention. Children who use disposable diapers every day are particularly sensitive
A model for low-energy thick-target bremsstrahlung produced in a scanning electron microscope

Thick-target bremsstrahlung measurements were obtained for various atomic numbers and for energies between 10 and 25 keV. A Jeol JSM 6100 scanning electron microscope was used for the electron beam and a Oxford Instruments Link Si(Li) detector for the bremsstrahlung spectrum. The experimental data were compared with a model that computes the thick-target bremsstrahlung spectrum by integrating the tabulated relativistic partial-wave doubly differential cross-section for thin-target bremsstrahlung over the target taking electron energy loss into account in the continuous slowing down approximation. The model corrects for electron backscattering, x-ray attenuation in the target and the efficiency of the x-ray detector. Very good agreement was found between the model and the experimental results. Extension of the model to consider multiple scattering in the target is also discussed. Copyright © 2001 John Wiley & Sons, Ltd.PublishedN/
Ady2p is essential for the acetate permease activity in the yeast Saccharomyces cerevisiae

To identify new genes involved in acetate uptake in Saccharomyces cerevisiae, an
analysis of the gene expression profiles of cells shifted from glucose to acetic acid
was performed. The gene expression reprogramming of yeast adapting to a poor
non-fermentable carbon source was observed, including dramatic metabolic changes,
global activation of translation machinery, mitochondria biogenesis and the induction of
known or putative transporters. Among them, the gene ADY2/YCR010c was
identified as a new key element for acetate transport, being homologous to the
Yarrowia lipolytica GPR1 gene, which has a role in acetic acid sensitivity. Disruption of
ADY2 in S. cerevisiae abolished the active transport of acetate. Microarray analyses of
ady2 strains showed that this gene is not a critical regulator of acetate response and
that its role is directly connected to acetate transport. Ady2p is predicted to be a
membrane protein and is a valuable acetate transporter candidate
Isolation of an acetyl-CoA synthetase gene (ZbACS2) from Zygosaccharomyces bailii

A gene homologous to Saccharomyces cerevisiae ACS genes, coding for acetyl-CoA
synthetase, has been cloned from the yeast Zygosaccharomyces bailii ISA 1307, by
using reverse genetic approaches. A probe obtained by PCR amplification from Z.
bailii DNA, using primers derived from two conserved regions of yeast ACS proteins,
RIGAIHSVVF (ScAcs1p; 210–219) and RVDDVVNVSG (ScAcs1p; 574–583), was
used for screening a Z. bailii genomic library. Nine clones with partially overlapping
inserts were isolated. The sequenced DNA fragment contains a complete ORF of
2027 bp (ZbACS2) and the deduced polypeptide shares significant homologies with
the products of ACS2 genes from S. cerevisiae and Kluyveromyces lactis (81%
and 82% identity and 84% and 89% similarity, respectively). Phylogenetic analysis
shows that the sequence of Zbacs2 is more closely related to the sequences from
Acs2 than to those from Acs1 proteins. Moreover, this analysis revealed that the
gene duplication producing Acs1 and Acs2 proteins has occurred in the common
ancestor of S. cerevisiae, K. lactis, Candida albicans, C. glabrata and Debaryomyces
hansenii lineages. Additionally, the cloned gene allowed growth of S. cerevisiae Scacs2
null mutant, in medium containing glucose as the only carbon and energy source,
indicating that it encodes a functional acetyl-CoA synthetase. Also, S. cerevisiae cells
expressing ZbACS2 have a shorter lag time, in medium containing glucose (2%,
w/v) plus acetic acid (0.1–0.35%, v/v). No differences in cell response to acetic acid
stress were detected both by specific growth and death rates. The mode of regulation
of ZbACS2 appears to be different from ScACS2 and KlACS2, being subject to
repression by a glucose pulse in acetic acid-grown cells. The nucleotide sequence
of a common 5269 bp fragment has been deposited in the EMBL Data Library under
Accession No. AJ314837.Fundação para a Ciência e a Tecnologia (FCT) - PRAXIS XXI P/AGR/11135/9
A genomic study of the Inter-ORF distances in Saccharomyces cerevisiae

The genome of eukaryotic microbes is usually quite compacted. The yeast Saccharomyces cerevisiae is one of the best-known examples. Open reading frames (ORFs) occupy about 75% of the total DNA sequence. The existence of other, non-protein coding genes and other genetic elements leaves very little space for gene promoters and terminators. We have performed an in silico study of inter-ORF distances that shows that there is a minimum distance between two adjacent ORFs that depends on the relative orientation between them. Our analyses suggest that different kinds of promoters and terminators exist with regard to their length and ability to overlap each other. The experimental testing of some putative exceptions to the minimum length model in tandemly orientated ORF pairs suggests that, in those cases, defects in promoter or terminator functionality exist that provoke transcription of polycistronic mRNAs
Role of Rho GTPases and Rho-GEFs in the regulation of cell shape and integrity in fission yeast

El pdf del artículo es la versión pre-print.The Rho family of GTPases are highly conserved molecular switches that control some of the most fundamental processes of cell biology, including morphogenesis, vesicular transport, cell division and motility. Guanine nucleotide-exchange factors (GEFs) are directly responsible for the activation of Rho-family GTPases in response to extracellular stimuli. In fission yeast, there are seven Dbl-related GEFs and they activate six Rho-type GTPases within a particular spatio-temporal context. The failure to do so might have consequences reflected in aberrant phenotypes and in some cases lead to cell death. In this review, we briefly summarize the role of Rho GTPases and Rho-GEFs in the establishment and maintenance of cell polarity and cell integrity in Schizosaccharomyces pombe. Copyright Â© 2006 John Wiley & Sons, Ltd.P. Garcia and I. Garcia were supported by a fellowship from the Junta de Castilla y León and V. Tajadura acknowledges support from a fellowship granted by the Ministerio de Educación y Ciencia, Spain. This work was supported by Grant BFU2005-01557 from the Comisión Interministerial de Ciencia y Tecnología, Spain, and CSI02C05 from the Junta de Castilla y León.Peer Reviewe
Genetic characterization of commercial saccharomyces cerevisiae isolates recovered from vineyard environments

One hundred isolates of the commercial S. cerevisiae strain Zymaflore VL1 were recovered from spontaneous fermentations carried out with grapes collected from vineyards located close to wineries in the Vinho Verde Wine Region (Portugal). Isolates were differentiated based on their mitochondrial DNA restriction patterns and the evaluation of genetic polymorphisms was carried out by microsatellite analysis, interdelta sequence typing and pulse field gel electrophoresis. Genetic patterns were compared to the ones obtained for 30 isolates of the original commercialized Zymaflore VL1 strain. Among the 100 recovered isolates we found a high percentage of chromosomal size variations, most evident for the smaller chromosomes III and VI. Complete loss of heterozygosity was observed for two isolates that also lost chromosomal heteromorphism; their growth and fermentative capacity in a synthetic must medium was also affected. Considerably higher number of variant patterns for interdelta sequence amplifications was obtained for grape-derived strains compared to the original VL1 isolates. 
Our data show that the permanence of strain VL1 in natural grapevine environments induced genetic changes that can be detected different fingerprinting methods. The observed genetic changes may reflect adaptive mechanisms to changed environmental conditions that yeast cells encounter during their permanence in nature.This study was funded by the programs POCI 2010 (FEDER/FCT, POCI/AGR/56102/2004) and AGRO (ENOSAFE, No. 762), Portugal
The transcriptional inhibitor thiolutin blocks mRNA degradation.

Thiolutin is commonly used as a general inhibitor of transcription in yeast. It has been used to calculate mRNA decay rates by stopping the transcription and then determining the relative abundance of individual mRNAs at different times after inhibition. We report here that thiolutin is also an inhibitor of mRNA degradation, and thus its use can lead to miscalculations of mRNA half-lives. The inhibition of mRNA decay seems to affect the mRNA degradation pathway without impeding poly(A) shortening, given that the decay rate of total poly(A) amount is not reduced by thiolutin. Moreover, the thiolutin-dependent inhibition of mRNA degradation has variable effects on different functional groups of genes, suggesting that they use various degradation pathways for their mRNAs
酵母Saccharomyces cerevisiaeの環境ストレスに対するトレハロース蓄積の効果に関する研究

This is the author's version of a work that was accepted for publication in Yeast. 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 Yeast, VOLUME 26, ISSUE 1, 2009, DOI：10.1002/yea.1646Siraje Arif Mahmud, Takashi Hirasawa, Hiroshi Shimizu. “High constitutive trehalose is required for resistance to multiple stresses in Saccharomyces cerevisiae,” Asia Pacific Biochemical Engineering Conference (APBioChEC’09), Kobe, Japan, November 24-28,2009. SB-P2, P. S16