Deep learning-based identification of sinoatrial node-like pacemaker cells from SHOX2/HCN4 double-positive cells differentiated from human iPS cells.

Background: Cardiomyocytes derived from human iPS cells (hiPSCs) include cells showing SAN- and non-SAN-type spontaneous APs. Objectives: To examine whether the deep learning technology could identify hiPSC-derived SAN-like cells showing SAN-type-APs by their shape. Methods: We acquired phase-contrast images for hiPSC-derived SHOX2/HCN4 double-positive SAN-like and non-SAN-like cells and made a VGG16-based CNN model to classify an input image as SAN-like or non-SAN-like cell, compared to human discriminability. Results: All parameter values such as accuracy, recall, specificity, and precision obtained from the trained CNN model were higher than those of human classification. Conclusions: Deep learning technology could identify hiPSC-derived SAN-like cells with considerable accuracy.

Prediction of conversion to Alzheimer's disease using deep survival analysis of MRI images.

The prediction of the conversion of healthy individuals and those with mild cognitive impairment to the status of active Alzheimer's disease is a challenging task. Recently, a survival analysis based upon deep learning was developed to enable predictions regarding the timing of an event in a dataset containing censored data. Here, we investigated whether a deep survival analysis could similarly predict the conversion to Alzheimer's disease. We selected individuals with mild cognitive impairment and cognitively normal subjects and used the grey matter volumes of brain regions in these subjects as predictive features. We then compared the prediction performances of the traditional standard Cox proportional-hazard model, the DeepHit model and our deep survival model based on a Weibull distribution. Our model achieved a maximum concordance index of 0.835, which was higher than that yielded by the Cox model and comparable to that of the DeepHit model. To our best knowledge, this is the first report to describe the application of a deep survival model to brain magnetic resonance imaging data. Our results demonstrate that this type of analysis could successfully predict the time of an individual's conversion to Alzheimer's disease.

Visualization of cancer-related chemical components in mouse pancreas tissue by tapping-mode scanning probe electrospray ionization mass spectrometry.

Mass spectrometry imaging is an informative approach for the comprehensive analysis of multiple components inside biological specimens. We used novel tapping-mode scanning probe electrospray ionization mass spectrometry method to visualize cancer-related chemical components in the mouse pancreas tissue section at a sampling pitch of 100 µm. Positive ion mode measurements from m/z 100 to 1500 resulted in the visualization of multiple components that are tentatively assigned as polyamines, lipids and proteins. Their signal intensities inside the cancerous and the non-cancerous regions were found to be significantly different by the two-sample t-test.

Correction: Imaging mass spectrometry of a mouse brain by tapping-mode scanning probe electrospray ionization.

Correction for 'Imaging mass spectrometry of a mouse brain by tapping-mode scanning probe electrospray ionization' by Yoichi Otsuka et al., Analyst, 2014, 139, 2336-2341.

Imaging mass spectrometry of a mouse brain by tapping-mode scanning probe electrospray ionization.

Methods for ambient sampling and ionization enable chemical information to be obtained with minimal sample preparation. Also, imaging mass spectrometry (IMS) enables the spatial distribution of multiple components to be determined by a single measurement. Here, we report an improved method of tapping-mode scanning probe electrospray ionization (t-SPESI) for ambient sampling and ionization in which probe oscillation is stabilized by using a piezo actuator. We demonstrate negative-mode IMS of a mouse coronal brain section and show that, compared with desorption electrospray ionization, t-SPESI provides unique features in the mass spectra: signal enhancement of fatty acid and lipids, and formation of multivalent ions tentatively assigned to gangliosides. These results would indicate the capability for the generation of multiple types of ions with t-SPESI.

Scanning probe electrospray ionization for ambient mass spectrometry.

RATIONALE: Ambient sampling and ionization techniques have been attracting attention in imaging mass spectrometry because they offer the advantage of rapid testing. We have developed a method which exploits the fluid motion of charged solvents for both local sampling and ionization with a single vibrating capillary probe. METHODS: The capillary probe was used to supply solvents in order to form a liquid bridge between the probe and a sample surface. A bias voltage was applied to the solvents to generate electrospray ionization (ESI). The probe was also vibrated by either an ultrasonic transducer fixed at the back of the sample (contact-mode) or spontaneous vibration of probe itself (tapping-mode). The ions generated by ESI were detected by a triple quadrupole mass spectrometer. RESULTS: Sampling of the specimens at the liquid bridge and ESI of the dissolved solutions both occurred around the probe apex. The sampling and ionization co-existed in contact-mode, while they were explicitly separated in the tapping-mode. The one-dimensional mapping of solid samples such as protein films and tissue sections was demonstrated. The results indicated that there was little cross-contamination during the operation. CONCLUSIONS: The method, named scanning probe electrospray ionization (SPESI), promises to be a simple and unique approach toward direct sampling and ionization methodology.

Recombination of an Fe-Si-P linkage to an Fe-P-Si linkage through an isolable intermediate phosphasilaferracyclopropane.

Phosphasilaferracycle [Cp*(CO)Fe{kappa(2)Si,P-SiMe(2)PPh(2)}], prepared upon irradiation of [Cp*(CO)(2)FeSiMe(2)PPh(2)], was converted to [Cp*(CO)(2)FeP(Ph)SiMe(2)Ph] under mild conditions. The unusual recombination of the iron, silicon, and phosphorus cores could be achieved through a sequence of 1,2- and 1,3-group migrations in an FeSiP system.

Stereoselective synthesis of 2,3,7-trimethylcyclooctanone and related compounds and determination of their relative and absolute configurations by the MalphaNP acid method.

The copper/chiral phosphoramidite (L(1))-catalyzed conjugate addition of dimethylzinc to cycloocta-2,7-dienone 4, followed by the methylation of the intermediate enolate, yielded a single isomer of 7,8-dimethylcyclooct-2-enone (+)-5. Compound (+)-5 was subjected to the second conjugate addition with ent-L(1) giving only one stereoisomer of 2,3,7-trimethylcyclooctanone (+)-6, which was converted to 2,3,7-trimethylcyclooctanol 7. To determine the relative and absolute configurations of these compounds, the (1)H NMR anisotropy method using (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid {(S)-(+)-MalphaNP acid} 1 was applied. Racemic alcohol (+/-)-7 was esterified with (S)-(+)-MalphaNP acid 1 yielding diastereomeric esters, which were efficiently separated by HPLC on silica gel affording the first-eluted MalphaNP ester (-)-10a and the second-eluted one (-)-10b. The relative and absolute configurations of ester (-)-10a were determined to be (S;1R,2S,3R,7S) by analyzing the (1)H and (13)C NMR spectra of (-)-10a and (-)-10b, especially their HSQC-TOCSY and NOESY spectra, and by applying the MalphaNP anisotropy method. The alcohol 7 formed from (+)-6 was similarly esterified with (S)-(+)-MalphaNP acid 1 yielding an MalphaNP ester, which was identical with (-)-10a, and the relative and absolute configurations of 2,3,7-trimethylcyclooctanone (+)-6 were determined to be (2S,3R,7S).

Synthesis of enantiopure 2-aryl-2-methoxypropionic acids and determination of their absolute configurations by X-ray crystallography.

Racemic 2-aryl-2-methoxypropionic acids were enantioresolved by the use of (S)-(-)-phenylalaninol 4. For instance, racemic 2-methoxy-2-phenylpropionic acid (+/-)-7 was condensed with phenylalaninol (S)-(-)-4 yielding a diastereomeric mixture of amides, which was easily separated by HPLC on silica gel affording the first-eluted amide (-)-13a and the second-eluted amide (+)-13b: alpha = 3.19, Rs = 3.49. The absolute configuration of amide (-)-13a was determined to be (R;S) by X-ray crystallography by reference to the S configuration of the phenylalaninol moiety. Amide (R;S)-(-)-13a was converted to oxazoline (R;S)-(-)-14a, from which enantiopure 2-methoxy-2-phenylpropionic acid (R)-(-)-7 was recovered. Other 2-aryl-2-methoxypropionic acids, (R)-(-)-8, (R)-(-)-9, (R)-(+)-10, (R)-(-)-11, and (R)-(-)-12, were similarly prepared in enantiopure forms with the use of phenylalaninol (S)-(-)-4, and their absolute configurations were clearly determined by X-ray crystallography or by chemical correlation.

New route to enantiopure MalphaNP acid, a powerful resolution and chiral 1H NMR anisotropy reagent.

MalphaNP acid (+/-)-1, 2-methoxy-2-(1-naphthyl)propionic acid, was enantioresolved by the use of phenylalaninol (S)-(-)-4; a diastereomeric mixture of amides formed from acid (+/-)-1 and amine (S)-(-)-4 was easily separated by fractional recrystallization and/or HPLC on silica gel, yielding amides (R;S)-(-)-5a and (S;S)-(+)-5b. Their absolute configurations were determined by X-ray crystallography by reference to the S configuration of the phenylalaninol moiety. Amide (R;S)-(-)-5a was converted to oxazoline (R;S)-(+)-8a, from which enantiopure MalphaNP acid (R)-(-)-1 was recovered. In a similar way, enantiopure MalphaNP acid (S)-(+)-1 was obtained from amide (S;S)-(+)-5b. These reactions provide a new route for the large-scale preparation of enantiopure MalphaNP acid, a powerful chiral reagent for the enantioresolution of alcohols and simultaneous determination of their absolute configurations by (1)H NMR anisotropy.

Synthesis of enantiopure phthalides including 3-butylphthalide, a fragrance component of celery oil, and determination of their absolute configurations.

Enantiopure phthalides 2 and 5-8 were synthesized via enantioresolution of the corresponding alcohols with a chiral auxiliary of camphorsultam dichlorophthalic acid, (1S,2R,4R)-(-)-CSDP acid 3, followed by solvolysis with KOH in MeOH and the catalytic oxidation of chiral glycols with iridium complex 28. The absolute configurations of phthalides 2 and 5-8 were determined by applying the (1)H-NMR anisotropy method of MalphaNP acid (4), 2-methoxy-2-(1-naphthyl)propionic acid, to the chiral synthetic precursory alcohols. In the case of 3-phenylphthalide (R)-(-)-7, the absolute configuration determined by the (1)H-NMR anisotropy method using MalphaNP acid 4 agreed with that by the X-ray crystallographic method. By applying these methods, 3-butylphthalide (S)-(-)-2, a fragrance component of essential oil of celery, has been synthesized in an enantiopure form, and its absolute configuration was unambiguously determined.

Phosphasilaferracyclopropane: an activator of small molecules having polarized single, double, and aromatic unsaturated bonds.

Irradiation of Cp*(CO)2FeSiMe2PPh2 resulted in the formation of phosphasilaferracyclopropane 2, which readily reacted with small organic molecules with polarized bonds to yield 3-5.

Enantioresolution of fluorinated diphenylmethanols and determination of their absolute configurations by X-Ray crystallographic and 1H NMR anisotropy methods.

Various fluorinated diphenylmethanols were enantioresolved by the methods of chiral camphorsultam-dichlorophthalic acid (CSDP acid) and/or 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid) yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X-ray crystallography of CSDP esters and/or by the (1)H NMR anisotropy method of MalphaNP esters for the first time.