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We investigated decline in the visual function of eyes with retrodots (RDs)-a subtype of cataract.This study included 57 eyes with RD opacity only (mean age 72.3 ± 5.2 years) and 34 eyes with transparent lenses (mean age 71.4 ± 3.7 years). A physician diagnosed lens opacity. Using the Kanazawa Medical University Classification and Grading System, the eyes were classified into the RD-1 (37 eyes, RDs25% of the 3-mm pupil area) and RD-2 (20 eyes, RDs ≥25% of the 3-mm pupil area) groups. Corrected distance visual acuity, contrast visual acuity, ocular refractive power, lens power, straylight, and backward light-scattering intensity and their relationship with visual function decline and optical characteristics of the eyeball were evaluated.Corrected distance visual acuity was significantly lower in the RD eyes than in controls. Contrast visual acuity decreased significantly in the RD-2 eyes in all environments and in the RD-1 eyes in the evening (EVE) and EVE + glare. Straylight was significantly higher in the RD-2 eyes than in the controls and RD-1 eyes but not different between the RD-1 eyes and controls. The RD-2 eyes were significantly more myopic than the controls and RD-1 eyes.When the opacity of RD eyes is ≥25%, the visual acuity and contrast visual acuity decrease and straylight increases. Furthermore, myopia occurs as the refractive power of the lens increases. Moreover, visual function decline may be due to an increase in the straylight value, which is necessary for determining surgical indications.

A protein synthesis system is one of the most important and complex biological networks, which translates DNA-encoded information into specific functions. Here, ePURE_JSBML, a tool for constructing biologically relevant large-scale and detailed computational models based on a reconstituted cell-free protein synthesis system, is presented; the user can specify the mRNA sequence, initial component concentration, and decoding rule. Model construction is based on Systems Biology Markup Language (SBML) using JSBML, a pure Java programming library. The tool generates simulation files, executable with Matlab, that enable a variety of simulation experiments including the synthesis of proteins of a few hundred residues.

For rational drug design, it is essential to predict the binding mode of protein-ligand complexes. Although various machine learning-based models have been reported that use convolutional neural networks (deep learning) to predict binding modes from three-dimensional structures, there are few detailed reports on how best to construct and use datasets. Here, we examined how different datasets affected the prediction of the binding mode of CYP3A4 by a three-dimensional neural network when the number of crystal structures for the target protein was limited. We used four different training datasets: one large, general dataset containing various protein complexes and three smaller, more specific datasets containing complexes with CYP3A4-like pockets, complexes with CYP3A4-binding ligands, and complexes with CYP protein family members. We then trained models with different combinations of datasets with or without subsequent fine-tuning and evaluated the binding mode prediction performance of each model. The best receiver operating characteristic (ROC) area under the curve (AUC) model with respect to area under the receiver operating characteristic curve was obtained by training with a combination of the general protein and CYP family datasets. However, the ROC AUC-recall balanced model was obtained by training with this combination of datasets followed by fine-tuning with the CYP3A4-binding ligands dataset. Our results suggest that datasets that balance protein functionality and data size are important for optimizing binding mode prediction performance. In addition, datasets with large median binding pocket sizes may be important for the binding mode prediction specifically of CYP3A4.

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., Over the past two decades, scientists from different fields have been developing SBML, a standard format for encoding computational models in biology and medicine. This article summarizes recent progress and gives perspectives on emerging challenges.

Biological systems are driven by multiple components and interactions that form a complex reaction network. We developed a method to analyze their dynamics by focusing on the component in temporal plateaus, or a quasi-stationary state (QSS). The analyses, using a computational model of a minimal in vitro protein synthesis system, showed that components in a QSS form clusters that grow over time. However, the growth is not in a linear fashion: The process involved collapse and regrowth of the formed clusters, where the collapse was closely related to the phase transition in the reaction network. These observations suggest that the studies focusing on the QSS might be useful for understanding of complex reaction dynamics.

The microstructure of materials affects thermal and electrical transport as well as the physical properties. The effects of the microstructure on both thermal and electrical transport in silicon membranes with periodic microporous structures produced from silicon-on-insulator wafers using microfabrication processes were studied. The in-plane thermal and electrical conductivities of the Si membranes were measured simultaneously by using a self-heating method. The measured thermal conductivity was compared with the result from the periodically laser-heating method. The thermal and electrical conductivities were much lower in the porous membranes than in the non-porous membrane. The measured thermal conductivity was much lower than expected based on values determined using classical models. A significant phonon size effect was observed even in microsized structures, and the mean free path for phonons was very long. It was concluded that phonon transport is quasi-ballistic and electron transport is diffuse in microporous Si structures. It was suggested that the microstructure had a different effect on thermal and electrical transport.

Purpose To investigate visual function in eyes with three subtypes of waterclefts (WCs). Methods Of patients in Kanazawa Medical University Hospital (2013-2017) and participants of Monzen Eye Study (2013-2016), 77 transparent lenses, mean age 66.7 years, and 70 eyes with only WC opacity of 70 patients, mean age 68.1 years, divided into peripheral-, central-, and total-type WC groups, were analyzed. Opacity was classified by one ophthalmologist using slit-lamp microscopy. Corrected-distance visual acuity (CDVA), contrast visual acuity (CVA), spherical equivalent (SE), astigmatism values, corneal refractive power (CP), axial length (AL), straylight, backward light scattering (BLS), and higher order aberrations (HOA) were measured and lenticular refractive power (LP) was calculated based on the values of AL, CP, and SE. Results Central-type WC showed significant decrease in CDVA and CVA and increase in straylight compared with control. Total-type WC showed significant decreases in CDVA, CVA, and LP, and increase in straylight, compared with control and peripheral-type WC. Total- and central-type WCs had significantly higher ocular total HOA and total-type WC had significantly higher internal total HOA than control. HOA correlated positively with CDVA (P < 0.001) and straylight (P = 0.020), and CDVA negatively with straylight in eyes with WCs (P = 0.008). Conclusions Total-type WC was associated with decreased LP, causing hyperopia, decreased CDVA and higher straylight; thus, such lenticular change should be considered for surgery indication. Significant correlations between HOA and both CDVA and straylight suggested increased HOA may decrease visual function in eyes with WCs.

Context is critical if researchers need toknow the specificity or responsiveness of atarget within a pathway.This is somethingthat has yet to be captured by anyinformatics system,but it will invariably betied to greater utility and even IP definitionsin the near future.To a large extent,pathways data and knowledge managementare seen to go hand in hand,both being usedto make important decisions,and bothrelying on context.It is interesting toconsider that perhaps we are witnessing theemergence of a new informatics paradigm,where knowledge becomes a formallydefined and well-shared scientific andeconomic asset.The third topic that was discussed by afew was the development of new ITstrategies to improve informaticsinfrastructure within large companies.Several speakers presented new andeffective methodologies to design and buildcomplex informatics systems that willeventually become the backbone of drugdiscovery platforms.Richard Ashe describedaccelerated software development programswithin GSK (http://www.gsk.com/) that canadapt more effectively to changing discoveryrequirements.Using lightweightmethodologies and web-based servicesrather than monolithic designing principles,projects could be defined and completedfaster within an ever-changing world ofneeds.Roy Dunbar,CIO of Eli Lilly(http://www.lilly.com/) proposes moreeffective collaborations between IT andscientists to create applications that havemore utility.Juergen Seega from AbbottLaboratories (http://abbott.com/) described‘keeping the scientific and IT worlds in sync’,rather than at odds.Taken together,IT isprogressing from being hidden in thebackwaters of software tinkering,tobecoming a major strategic partner withindrug discovery environments.Other issues were addressed,includinggood laboratory practices as related toinformatics,electronic notebooks,intelligent storage and use of high-throughput screening data,and IP portfoliomanagement.Based on the presentations atthe conference,it was clear that theapplications and benefits of informatics forthe pharmaceutical industry are growing,and that informatics promises to be a keyfactor for the future success of drugdiscovery.Systems biology is characterized by synergisticintegration of theory,computational modeling,and experiment [1].Although softwareinfrastructure is one of the most crucialcomponents of systems biology research,there has been no common infrastructureor standard to enable integration ofcomputational resources.To solve thisproblem,the Systems Biology MarkupLanguage (SBML) [2] and Systems BiologyWorkbench (SBW) have been developed[3].SBML is an open,XML-based format forrepresenting biochemical reaction networks,and SBW is a modular,broker-based,message-passing framework for simplifiedintercommunication between applications.Several simulation and analysis softwarepackages already support SBML (Level-1)and SBW,or are being developed to supportthem.Identification of the logic and dynamics ofgene-regulatory and biochemical networks isa major challenge of systems biology.Webelieve that such network building tools andsimulation environments using standardizedtechnologies play an important role in thesoftware platform of systems biology.As onesuch approach,we have developedCellDesigner,a process diagram editor forgene-regulatory and biochemical networks.In the following,we will introduce themain features of CellDesigner.The mostcrucial elements are that it is a system ofBIOSILICO Vol.1, No.5 November 2003

Among various approaches in proving gauge independence, models containing an explicit gauge dependence are convenient. The well-known example is the gauge parameter in the covariant gauge fixing which is of course most suitable for the perturbation theory but a negative metric prevents us from imaging a dynamical picture. Noncovariant gauge such as the Coulomb gauge is on the contrary used for many physical situations. Therefore it is desirable to include both cases. More than ten years ago, Steinmann introduced a function (distribution) which can play this role in his attempt on discussing quantum electrodynamics (QED) in terms of the gauge invariant fields solely. The method is, however, broken down in the covariant case: the invariant operators are ill-defined because of 1/p^2 singularity in the Minkowski space. In this paper, we apply his function to the path integral: utilizing the arbitrariness of the function we first restrict it to be able to have a well- defined operator, and then a Hamiltonian with which we can build up the (Euclidean) path integral formula. Although the formula is far from covariant, a full covariant expression is recovered by reviving the components which have been discarded under the construction of the Hamiltonian. There is no pathological defects contrary to the operator formalism. With the aid of the path integral formula, the gauge independence of the free energy as well as the S-matrix is proved. Moreover the reason is clarified why it is so simple and straightforward to argue gauge transformations in the path integral. Discussions on the quark confinement is also presented., Comment: 15 pages, 5 figure files, LaTeX

We study on estimation of greenhouse gas emissions in micro-fabrication of MEMS devices. The estimation is made on a test element groups of silicone-based sensors fabricated on an 8-inch SOI wafer at the green 8-inch MEMS prototype station. The estimation includes electric power, materials, and consumables used in fabrication equipments as well as contribution from usage of cleanroom’s facilities such as supply and waste disposal. The estimation is also made separately in each process steps. The result shows that electric power and purified nitrogen are major sources of greenhouse gas emissions. Our process-by-process approach for the estimation enables us to identify major sources in each process to reduce emissions.

Skeletal muscle satellite cells play key roles in postnatal muscle growth and regeneration. To study molecular regulation of satellite cells, we directly prepared satellite cells from 8- to 12-week-old C57BL/6 mice and performed genome-wide gene expression analysis. Compared with activated/cycling satellite cells, 507 genes were highly upregulated in quiescent satellite cells. These included negative regulators of cell cycle and myogenic inhibitors. Gene set enrichment analysis revealed that quiescent satellite cells preferentially express the genes involved in cell-cell adhesion, regulation of cell growth, formation of extracellular matrix, copper and iron homeostasis, and lipid transportation. Furthermore, reverse transcription-polymerase chain reaction on differentially expressed genes confirmed that calcitonin receptor (CTR) was exclusively expressed in dormant satellite cells but not in activated satellite cells. In addition, CTR mRNA is hardly detected in nonmyogenic cells. Therefore, we next examined the expression of CTR in vivo. CTR was specifically expressed on quiescent satellite cells, but the expression was not found on activated/proliferating satellite cells during muscle regeneration. CTR-positive cells reappeared at the rim of regenerating myofibers in later stages of muscle regeneration. Calcitonin stimulation delayed the activation of quiescent satellite cells. Our data provide roles of CTR in quiescent satellite cells and a solid scaffold to further dissect molecular regulation of satellite cells. Disclosure of potential conflicts of interest is found at the end of this article.

In order to estimate the effect of dynamical gluons on chiral condensates, the gap equation of the $\mathrm{SU}(2)$ gauged Nambu--Jona-Lasinio model, under a constant background non-Abelian magnetic field, is investigated up to the two-loop order in $2+1$ and $3+1$ dimensions. We set up a general formulation allowing both cases of electric as well as magnetic background fields. We employ the proper time method which gives a gauge-invariant fermionic functional determinant. In $3+1$ dimensions chiral symmetry breaking $(\ensuremath{\chi}\mathrm{SB})$ is enhanced by gluons even in a zero background magnetic field and becomes more striking as the background field grows larger. In $2+1$ dimensions gluons also enhance $\ensuremath{\chi}\mathrm{SB}$ but the dependence on the background field is not simple; dynamical mass is not a monotone function of a background field for a fixed four-Fermi coupling.

The chiral symmetry breaking in the 4-dimensional QED with the chirally invariant four-fermion interaction is discussed by using a novel path integral expression in terms of the field-strength tensor. In the local potential approximation, we find that the chiral symmetry is spontaneously broken for any nonzero gauge and four-fermion couplings on the tree level of an auxiliary field $\sigma$. The present approach allows us to easily include higher orders of the gauge coupling so that the effective potential up to the sixth order is obtained., Comment: 18 pages, 2 figures

Critical dynamics of the Nambu-Jona-Lasinio model, coupled to a constant electromagnetic field in D=2, 3, and 4, is reconsidered from a viewpoint of infrared behavior and vacuum instability. The latter is associated with constant electric fields and cannot be avoidable in the nonperturbative framework obtained through the proper time method. As for magnetic fields, an infrared cut-off is essential to investigate the critical phenomena. The result reconfirms the fact that the critical coupling in D=3 and 4 goes to zero even under an infinitesimal magnetic field. There also shows that a non-vanishing $F_{\mu\nu}\widetilde F^{\mu\nu}$ causes instability. A perturbation with respect to external fields is adopted to investigate critical quantities, but the resultant asymptotic expansion excellently matches with the exact value., Comment: 27 pages, 17 figure files, LaTeX