Crystallization of Amorphous Nifedipine Under Isothermal Conditions: Inter-laboratory Reproducibility and Investigation of the Factors Affecting Reproducibility.

High inter-laboratory reproducibility is required for conducting collaborative experiments among several laboratories. The primary aim of our evaluation of the physical stability of amorphous drugs, conducted in co-operation with eight laboratories, was to establish a protocol for isothermal storage tests to obtain data of the same quality from all the participating laboratories. Sharing a protocol that contained the same level of detail as the experimental section of general papers was insufficient for high inter-laboratory reproducibility.

Influence of the crystallization tendencies of pharmaceutical glasses on the applicability of the Adam-Gibbs-Vogel and Vogel-Tammann-Fulcher equations in the prediction of their long-term physical stability.

Amorphization is a powerful approach for improving the aqueous solubility and bioavailability of poorly water-soluble compounds. However, it can cause chemical and physical instability, the latter of which can lead to crystallization during storage, diminishing the solubility advantage of the amorphous state. As there is no standard method for predicting the physical stability of amorphous materials, a long-term stability study is needed in drug development.

Tau Aggregation Correlates with Amyloid Deposition in Both Mild Cognitive Impairment and Alzheimer's Disease Subjects.

Background: Amyloid plaque and tau-containing neurofibrillary tangles are important features of Alzheimer's disease (AD). However, the relationship between these processes is still debated.

Objective: We aimed to investigate local and distant relationships between tau and amyloid deposition in the cortex in mild cognitive impairment (MCI) and AD using PET imaging.

Application of Co-Amorphous Technology for Improving the Physicochemical Properties of Amorphous Formulations.

Co-amorphous technology was recently introduced to stabilize drugs in the amorphous state for drug development. We examined the predictability of the formation of co-amorphous systems and identified two reliable indicators of successful formation: (1) a negative Δ H value and (2) small Δlog P between components. Moreover, we found that the stability of co-amorphous systems was improved when (1) Δ H was negative and (2) amorphous forms of the constituent compounds were stable.

Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease.

Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated.

The delirium and population health informatics cohort study protocol: ascertaining the determinants and outcomes from delirium in a whole population.

Background: Delirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline?

Methods: The Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden.

Isolation of equine peripheral blood stem cells from a Japanese native horse.

The sizes of Japanese native horses have drastically decreased, and protection of these populations is important for Japanese horse culture. Social trials as well as scientific attempts are necessary for maintaining the breed. Mesenchymal stem cells (MSCs) have potential as a cell source for various cell therapies.

Disease Compass- a navigation system for disease knowledge based on ontology and linked data techniques.

Background: Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states.

An ontological modeling approach for abnormal states and its application in the medical domain.

Background: Recently, exchanging data and information has become a significant challenge in medicine. Such data include abnormal states. Establishing a unified representation framework of abnormal states can be a difficult task because of the diverse and heterogeneous nature of these states.

The RIKEN integrated database of mammals.

The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the official undertaking to integrate its mammalian databases produced from multiple large-scale programs that have been promoted by the institute. The database integrates not only RIKEN's original databases, such as FANTOM, the ENU mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and the Bioresource Database, but also imported data from public databases, such as Ensembl, MGI and biomedical ontologies.

Ontological integration of data models for cell signaling pathways by defining a factor of causality called 'signal'.

Databases have collected masses of information concerning cell signaling pathways that includes information on pathways, molecular interactions as well as molecular complexes. However we have no general data model to represent comprehensive properties of cell signaling pathways, so that this type of information has been represented by two different data models that we call 'binary relation' and 'state transition'. The disagreement between the existing models derives from lack of consensus about a factor of causality in reactions in cell signaling pathways, which is often called 'signal'.

Optical control of two-photon excitation efficiency of alpha-perylene crystal by pulse shaping.

Optimized pulse shaping experiments were carried out on the control of two-photon excitation efficiency of an alpha-perylene crystal in the temperature region from 30 to 290 K. It was found that a pulse train with a pulse interval of 90 fs and an alternately reversing phase relation increased the excitation efficiency by a factor of 2 for the whole temperature region. The pulse shape characteristic for effective efficiency increase was reduced by double pulse experiments in which the dependence of the emission intensity on the pulse interval and relative phase between pulses were measured.

Cell signaling networks ontology.

Although databases for cell signaling pathways include numbers of reaction data of the pathways, the reaction data cannot be used yet to deduce biological functions from them. For the deduction, we need systematic and consistent interpretation of biological functions of reactions in cell signaling pathways in the context of "information transmission". To address this issue, we have developed a functional ontology for cell signaling pathways, Cell Signaling Network Ontology (CSN-Ontology), which provides framework for the functional interpretation presenting some important concepts as information, selectivity, movability, and signaling rules including passage of time.

Selective activation of two sites in RNA by acridine-bearing oligonucleotides for clipping of designated RNA fragments.

Artificial enzymes for selective scission of RNA at two designated sites, which are valuable for advanced RNA science, have been prepared by combining lanthanide(III) ion with an oligonucleotide bearing two acridine groups. When these modified oligonucleotides form heteroduplexes with substrate RNA, the two phosphodiester linkages in front of the acridines are selectively activated and preferentially hydrolyzed by lanthanide ion. This two-site RNA scission does not require any specific RNA sequence at the scission sites, and the length of clipped RNA fragment is easily and precisely controllable by changing the distance between two acridine groups in the modified oligonucleotide.

Tandem site-selective RNA scission utilizing acridine-DNA conjugates.

Useful technique to clip designated short RNA fragments from long substrates has been prepared by combining oligonucleotides bearing two acridine groups and lanthanide(III) ions. The substrate RNA is site-selectively activated at two designated phosphodiester linkages by complementary bis-acridine-modified DNA, and is promptly cleaved by lanthanide(III) ions to produce short RNA fragment between the two scission sites. By applying this technique, efficient genotyping method for single nucleotide polymorphism (SNP) have been developed.

Novel approach for SNP genotyping based on site-selective RNA scission.

Novel genotyping method for single nucleotide polymorphisms (SNPs), based on site-selective RNA scission, has been developed. A substrate RNA is activated at two sites by complementary acridine-modified DNA having two acridine residues, and is site-selectively cleaved by metal ion catalyst to produce short RNA fragment containing the SNP site. Genotype of the substrate is accurately and easily determined by mass analysis of the fragment.

Site-selective artificial ribonuclease using pinpoint RNA activation.

An acridine residue attached to the end or the inside of a DNA activates the target phosphodiester linkages in complementary RNA. Due to this pinpoint activation, the RNA is site-selectively and efficiently cleaved at these linkages by various free metal ions under mild condition. Spectroscopic analyses show that the acridine moiety is sandwiched between neighboring bases, and pushes the opposite nucleotide out of the hetero-duplex.