Bayesian inference is facilitated by modular neural networks with different time scales.

Various animals, including humans, have been suggested to perform Bayesian inferences to handle noisy, time-varying external information. In performing Bayesian inference by the brain, the prior distribution must be acquired and represented by sampling noisy external inputs. However, the mechanism by which neural activities represent such distributions has not yet been elucidated. Our findings reveal that networks with modular structures, composed of fast and slow modules, are adept at representing this prior distribution, enabling more accurate Bayesian inferences. Specifically, the modular network that consists of a main module connected with input and output layers and a sub-module with slower neural activity connected only with the main module outperformed networks with uniform time scales. Prior information was represented specifically by the slow sub-module, which could integrate observed signals over an appropriate period and represent input means and variances. Accordingly, the neural network could effectively predict the time-varying inputs. Furthermore, by training the time scales of neurons starting from networks with uniform time scales and without modular structure, the above slow-fast modular network structure and the division of roles in which prior knowledge is selectively represented in the slow sub-modules spontaneously emerged. These results explain how the prior distribution for Bayesian inference is represented in the brain, provide insight into the relevance of modular structure with time scale hierarchy to information processing, and elucidate the significance of brain areas with slower time scales.

Origin of an orbiting star around the galactic supermassive black hole.

The tremendous tidal force that is linked to the supermassive black hole (SMBH) at the center of our galaxy is expected to strongly subdue star formation in its vicinity. Stars within 1'' from the SMBH thus likely formed further from the SMBH and migrated to their current positions. In this study, spectroscopic observations of the star S0-6/S10, one of the closest (projected distance from the SMBH of ≈0''.3) late-type stars were conducted. Using metal absorption lines in the spectra of S0-6, the radial velocity of S0-6 from 2014 to 2021 was measured, and a marginal acceleration was detected, which indicated that S0-6 is close to the SMBH. The S0-6 spectra were employed to determine its stellar parameters including temperature, chemical abundances ([M/H], [Fe/H], [α/Fe], [Ca/Fe], [Mg/Fe], [Ti/Fe]), and age. As suggested by the results of this study, S0-6 is very old (≳10 Gyr) and has an origin different from that of stars born in the central pc region.

Surgical Punctal Occlusion; Combined Lacrimal Canaliculi Cauterization and Punctal Suturing for Severe Dry Eye.

Purpose: To evaluate the treatment outcome of surgical punctal occlusion with combined canaliculi ablation and punctal suturing in patients with severe dry eye. Methods: Eleven eyes of seven patients were diagnosed with severe dry eye with decreased lacrimal secretion and were refractory to treatment with various eye drops and/or had repeatedly experienced loss of punctal plugs, and continued to experience subjective symptoms received surgical punctal occlusion. In 20 puncta, lacrimal canaliculi ablation was performed along the entire length of the lacrimal canaliculus where a diathermy needle could be inserted. After resection of the annulus fibrosus in the peri-punctal area, tight cross-stitch suturing of the puncta was performed with 8-0 absorbent thread. Visual acuity, corneal staining score according to the area (A) and density (D) classification, and Schirmer tear test (STT); tear break up time (tBUT); and subjective symptoms assessed by the University of North Carolina (UNC) and Dry Eye Management Scale were compared before and one year after surgery. Results: Recanalization occurred in 1/20 puncta (5.0% at month 5) in 1/11 eyes. Student's t-test showed significant improvement at one year compared with preoperative values for LogMAR value (P = 0.019), corneal staining score A (P = 0.00003) and D (P = 0.0003), STT (P = 0.004), and subjective symptoms (P = 0.015). No change was shown in tBUT and no serious adverse event occurred. Conclusion: This improved, minimally invasive surgical procedure has a low recanalization rate and achieves both objective and subjective improvements at one year.

Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review.

The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural®, was launched in June 2021 in Japan. COMET was performed on two patients, including the first case in the post-marketing phase of Ocural®. Pathological and immunohistochemical examinations were also carried out using specimens obtained before and after COMET and the spare cell sheet. In case 1, the ocular surface remained free from epithelial defects for approximately six months. In case 2, although defect of the cornea-like epithelia was observed after COMET for one month, it was resolved after the insertion of lacrimal punctal plugs. In case 1, adjuvant treatment was interrupted due to an accident during the second month after COMET, resulting in conjunctival ingrowth and corneal opacity. Eventually, a lamellar keratoplasty was required at six months after COMET. Immunohistochemistry revealed the presence of markers for stem cells (p63, p75), proliferation (Ki-67), and differentiation (Keratin-3, -4, and -13) in both the cornea-like tissue after COMET and a cultivated oral mucosal epithelial cell sheet. In conclusion, Ocural® can be accomplished without major complications, and the stem cells derived from oral mucosa might be successfully engrafted.

Treatment for Intracorneal Hematoma by Anterior Chamber Gas Tamponade Combined With Keratocentesis.

PURPOSE: To report a new surgical method for intracorneal hematoma removal using combination of keratocentesis and gas tamponade in the anterior chamber. METHODS: We reviewed the clinical course and outcomes of surgical intervention. RESULTS: An 82-year-old woman visited our department because of a sudden decline in visual acuity (20/800 on the Snellen chart) in her left eye. We observed neovascularization from the superior corneal limbus and a hematoma near the Descemet membrane, deep in the stroma of the corneal center. Filtered air was injected into the anterior chamber, keratocentesis was performed at four locations from the corneal epithelium through the stroma, and the hematoma was removed from the puncture sites. The corneal hematoma disappeared, and the best-corrected visual acuity reached 20/20 at postoperative month 4. DISCUSSION: Combination of keratocentesis and gas tamponade in the anterior chamber is a simple and effective method for removing intracorneal hematomas.

Refractive Correction After Penetrating Keratoplasty by a New Soft Contact Lens with a Special Design for Astigmatism: A Case Report.

YOUSOFT is a new soft contact lens (CL) specifically designed for the correction of astigmatism. It is a conventional FDA Group II soft contact lens (SCL) and the optical zone in its centre is thick, and on its rear surface it has a prism ballast structure to prevent rotation. This lens was prescribed for a 59-year-old male on the eye with irregular corneal astigmatism after receiving penetrating keratoplasty (PKP) for refractive correction, whose eye was difficult to wear hard CLs (HCLs). After following the directions in the fitting manual provided by the manufacturer, fitting was good in the right eye and corrected visual acuity was 20/25 in Snellen Chart. He could continue wearing without CL discomfortable YOUSOFT may be useful in patients who have received PKP.

Dynamical Mechanism of Sampling-Based Probabilistic Inference Under Probabilistic Population Codes.

Animals make efficient probabilistic inferences based on uncertain and noisy information from the outside environment. It is known that probabilistic population codes, which have been proposed as a neural basis for encoding probability distributions, allow general neural networks (NNs) to perform near-optimal point estimation. However, the mechanism of sampling-based probabilistic inference has not been clarified. In this study, we trained two types of artificial NNs, feedforward NN (FFNN) and recurrent NN (RNN), to perform sampling-based probabilistic inference. Then we analyzed and compared their mechanisms of sampling. We found that sampling in RNN was performed by a mechanism that efficiently uses the properties of dynamical systems, unlike FFNN. In addition, we found that sampling in RNNs acted as an inductive bias, enabling a more accurate estimation than in maximum a posteriori estimation. These results provide important arguments for discussing the relationship between dynamical systems and information processing in NNs.

Arginine-mediated dissociation of single cells and cell sheets from a polystyrene culture dish.

Here, we report a novel non-enzymatic cell dissociation method, based on our finding that adherent cells dissociate rapidly from the polystyrene culture dish when incubated in an l- or d-arginine-containing solution. We also demonstrate the successful detachment of confluent NIH/3T3 cell monolayers from the culture dish as a cell sheet by the addition of an arginine solution.

Virtual Screening Techniques and Current Computational Infrastructures.

The drug discovery process in general is a very resource intensive undertaking that has existed for a very long time. In the last two decades, performing molecular simulations that determine the level of interaction between a protein and ligand have been refined to the point where they are now an essential part of the drug discovery process. These simulations serve to reduce the time to discovery and improve the positive "hit" rates when screening for molecule with biological activity. As a result, the chemical search space is greatly reduced in silico, prior to any in vitro experiments that validate the results. Recently, there have been many advances in computer science technologies that have improved the virtual screening process. This paper will give a brief overview of the virtual screening process and then summarize the current state-of-the-art technologies applied to virtual screenings. Both biomedical researchers and computer scientists can use this review as a guide to the implementation requirements for computational resources of virtual screening.

Interstrand cross-link of DNA by covalently linking a pair of abasic sites.

A pair of apurinic/apyrimidinic sites formed in DNA has been covalently connected with bis(aminooxy) derivatives. The efficacy of the interstrand cross-link is associated with the structural tethering of two aminooxy groups. The interstrand cross-link constructed stable DNA scaffolds for enzyme alignment.

Design of a grid service-based platform for in silico protein-ligand screenings.

Grid computing offers the powerful alternative of sharing resources on a worldwide scale, across different institutions to run computationally intensive, scientific applications without the need for a centralized supercomputer. Much effort has been put into development of software that deploys legacy applications on a grid-based infrastructure and efficiently uses available resources. One field that can benefit greatly from the use of grid resources is that of drug discovery since molecular docking simulations are an integral part of the discovery process. In this paper, we present a scalable, reusable platform to choreograph large virtual screening experiments over a computational grid using the molecular docking simulation software DOCK. Software components are applied on multiple levels to create automated workflows consisting of input data delivery, job scheduling, status query, and collection of output to be displayed in a manageable fashion for further analysis. This was achieved using Opal OP to wrap the DOCK application as a grid service and PERL for data manipulation purposes, alleviating the requirement for extensive knowledge of grid infrastructure. With the platform in place, a screening of the ZINC 2,066,906 compound "drug-like" subset database against an enzyme's catalytic site was successfully performed using the MPI version of DOCK 5.4 on the PRAGMA grid testbed. The screening required 11.56 days laboratory time and utilized 200 processors over 7 clusters.

A novel yeast-based reporter assay system for the sensitive detection of genotoxic agents mediated by a DNA damage-inducible LexA-GAL4 protein.

Yeast-based genotoxicity testing systems can sensitively detect DNA damaging agents in the environment. We have developed a novel "indirect" reporter assay system based on a recombinant yeast containing both a sensor and a reporter plasmid. The sensor plasmid contains a gene encoding the artificial transcription factor of the Escherichia coli LexA DNA binding domain fused to the transcriptional activation domain of yeast Gal4p, which is regulated by the DNA damage-inducible RNR2 promoter. The reporter plasmid contains the E. coli lacZ gene with the LexA binding site in the 5'-upstream region, allowing transcriptional activation by the induced LexA-GAL4 protein. The activity of DNA damage-dependent beta-galactosidase (beta-gal) in the "indirect" reporter assay system was compared with that of a current yeast-based "direct" reporter system. The "indirect" system exhibited 1.5- to 5-fold greater beta-gal activity upon induction by alkylating agents or camptothecin. To increase the sensitivity of the new reporter system further, several deletion yeast strains were tested, and enhanced induction of reporter activity was observed in DNA repair-deficient mag1Delta cells. The "indirect" 96-well microtiter plate assay system is a potentially inexpensive and sensitive method for detecting genotoxic activities in a wide range of compounds, and in polluted environmental samples.

Development of ecotoxicity assay based on inhibition of respiring activity in microbial community using XTT reduction.

The aim of this study is to develop ecotoxicity assay for evaluating the influence of chemicals on a microbial ecosystem based on XTT reduction inhibition (XTT assay). XTT reduction method is used for quantification of the microbial respiratory activity. Since the XTT assay indicates the inhibition of microbial respiratory activity, it could evaluate the toxicity of chemicals. Suitable conditions for the XTT assay were determined to be 200 mg/L of particulate organic carbon as test microbe concentration and 15 min of assay time using activated sludge. Toxicities of several chemicals evaluated by activated sludge as test microbes were examined under these conditions. Sensitivity for the toxicity evaluated by the XTT assay using activated sludge microbes was almost the same value was that for the OECD activated sludge respiration inhibition test (ASRI test). XTT assay was also applied for evaluating the influence of chemicals on the soil microbial community and the XTT assay was used to evaluate a median effective concentration (EC(50)) value of 3,5-dichlorophenol (3,5-DCP). The EC(50) value of 3,5-DCP was almost the same as the value using activated sludge as test microbes. These results suggest that the XTT assay using both mixed cultures of non-contaminated environments and chemical extracts from various contaminated environments could evaluate the influence on microbial ecosystems affected by toxic chemicals.