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Mild cognitive impairment (MCI) is a high-risk condition for conversion to Alzheimer's disease (AD) dementia. However, individuals with MCI show heterogeneous patterns of pathology and conversion to AD dementia. Thus, detailed subtyping of MCI subjects and accurate prediction of the patients in whom MCI will convert to AD dementia is critical for identifying at-risk populations and the underlying biological features. To this end, we developed a model that simultaneously subtypes MCI subjects and predicts conversion to AD and performed an analysis of the underlying biological characteristics of each subtype. In particular, a heterogeneous mixture learning (HML) method was used to build a decision tree-based model based on multimodal data, including cerebrospinal fluid (CSF) biomarker data, structural magnetic resonance imaging (MRI) data

Calcium monohydride is an astronomically important molecule. Despite the long history of work on this molecule, discrepancies still exist between experiment and theory for the higher vibrational levels of the B/B′2Σ+ state. We report on rotational-vibrational-electronic transitions to the B/B′2Σ+ state which we have assigned to the B/B′2Σ+ (v = 9, 10, 11 and 18) – X2Σ+ (v = 0) transitions. The energy spacing of the higher lying vibrational levels of the B/B′2Σ+ state alternates strongly with vibrational quantum number as predicted by the coupled-channel calculations of Carlsund-Levin et al. (2002). We confirm that this alternation extends all the way from v = 9 to v = 20.

The new experimental results and analysis of the microwave spectra of HCOO13CH3 in the second methyl torsional excited state are reported. Pseudo-principal axis method (pseudo-PAM) was successfully applied to the normal methyl formate in the second torsional excited state and again applied to this isotopologue. We succeeded to assign 536 A-species transitions up to J = 33 and Ka = 15 and 417 E-species transitions up to J = 32 and Ka = 14. Thirty parameters were used to do the least-squares-analysis by using the pseudo-PAM Hamiltonian consisting of rotational, centrifugal distortion, and internal-rotational constants.

We have performed high precision spectroscopy of lead oxide (PbO) molecules. The B(1) ( υ ′ = 3 - 6 ) - X ( 0 + ) ( υ ″ = 0 ) transitions located in 398–423 nm were investigated by using a cold and slow PbO beam. About 140 lines were measured by comparing with resonances of an ultralow expansion etalon, which allows us to determine absolute frequencies of these lines with the uncertainty of about 10 MHz. The υ ′ = 4 level has considerably different spectroscopic constants from other vibrational levels. This can be explained by a homogeneous perturbation due to a near-degenerate vibrational level in the a(1) state.

There are many sulfur-containing molecules identified in interstellar medium. However, methyl mercaptan (methanethiol, CH 3 SH) is so far, the only confirmed complex organic molecule and further study on its isotopologues would be worthwhile. With the aid of the new high-sensitivity telescopes, it may be possible to detect CD 3 SH since CD 3 OH was already detected. The rest frequencies of CD 3 SH are indispensable information. In the present study of CD 3 SH in the ground state, 484 A-species transitions and 581 E-species transitions up to J = 46 and K a = 10, were least-squares-analyzed by using the pseudo-principal axis method (PAM) Hamiltonian with 22 parameters consisting of rotational, centrifugal distortion, and internal-rotational constants.

Zeeman effect of the rotational spectrum of methanol has been measured in a magnetic field of 7.0 kG produced by rectangular bar magnets of neodymium. Thirty low J, K (J ≤ 10, K ≤ 3) rotational transitions, including those in the excited torsional states, were observed. Their Zeeman effect splittings were measured with uncertainties of about 5%, and the four diagonal elements of the rotational g tensor, including the effect of internal rotation of the methyl group, were determined. Using this g tensor, the g factors of low J, K levels can be calculated with an uncertainty of about 5%. They allow us to calculate Zeeman shifts of rotational transitions of methanol observed in interstellar space.

The microwave absorption spectrum of the trans-ethyl methyl ether in the skeletal torsional v30 = 2 state was analyzed for the first time. The trans-ethyl methyl ether molecule has two inequivalent methyl group internal rotors. Splitting due to the methyl group connected to the oxygen was dominant and observed in the v30 = 2 state. This result was supported by considering the torsional force field in the same way as in the ground and the v30 = 1 states. Over 800 lines up to J = 55 and Ka = 6 were assigned. The spectrum was analyzed using an IAM-like matrix formulation. Three rotational constants, eight centrifugal distortion constants, and four O-CH3 internal rotation tunneling parameters were determined for the v30 = 2 state. It was also made clear in the present analysis that the tunneling parameter dominant concerning the splitting due to the O-CH3 internal rotation has the same sign as that of the v30 = 1 state, and the sign opposite to that of the ground state.

Terahertz absorption spectroscopy was employed to measure the ground state pure rotational transitions of the water isotopologue HD 18 O . A total of 105 pure rotational transitions were observed in the 0.5–5.0 THz region with ∼ 100 kHz accuracy for the first time. The observed positions were fit to experimental accuracy using the Euler series expansion of the asymmetric-top Hamiltonian together with the literature Microwave, Far-IR and IR data in the ground state and ν 2 . The new measurements and predictions reported here support the analysis of astronomical observations by high-resolution spectroscopic telescopes such as SOFIA and ALMA where laboratory rest frequencies with uncertainties of 1 MHz or less are required for proper analysis of velocity resolved astrophysical data.

Despite the astrophysical importance of calcium monohydride (CaH), a long-standing discrepancy exists between the experimental and theoretical analysis of its first two excited 2 Σ + states. In a bid to resolve this discrepancy, we observed the rotationally-resolved laser-induced fluorescence spectrum of CaH in the 23,300–27,800 cm −1 region. We assigned all newly observed vibrational levels, and five levels previously assigned to the D state, to the B/B′ state. The level properties alternate strongly with vibrational excitation and this new assignment brings the experimental vibronic structure into remarkably good agreement with the predictions of Carlsund-Levin et al. (2002).

The trans -ethyl methyl ether has two inequivalent methyl internal rotors and shows tunneling splittings of maximum up to five components. However, the barrier of these two internal rotation potentials were relatively high and the five components were not resolved in the ground state microwave spectra. In this study, well-resolved Fourier transform microwave ground state spectrum was measured for the first time to resolve the five components. The ground state microwave spectra were reanalyzed based on these new measurements and the additional millimeter-wave spectra as well as those studied previously by Fuchs et al. Ninety Fourier transform microwave spectral lines were assigned to 107 transitions in the ground state and 3508 conventional microwave absorption lines were assigned up to K a = 16 of the ground state, including all 707 lines reported by Fuchs et al. In addition, 10 transitions were observed by the double resonance experiment. They were least-squares-analyzed by the use of an internal axis method (IAM)-like tunneling matrix formalism based on an extended permutation-inversion group theoretical idea. Twenty-two molecular parameters composed of rotational constants, centrifugal distortion constants, internal rotation parameters and internal rotation tunneling parameters were determined for the ground state. The microwave spectra in the three torsionally excited states, that is, the ν 28 = 1 C–CH 3 torsional state, the ν 29 = 1 O–CH 3 torsional state and the ν 30 = 1 skeletal torsional state, were also reanalyzed by using the IAM-like tunneling matrix formalism and somewhat extended line assignments.

The CD3SH molecule, an isotopologue of methyl mercaptan, may be detected in interstellar space with the aid of the new high-sensitivity telescopes. Following our previous microwave study for its ground vibrational state (J. Mol. Spectrosc. 337(2017) 32–36), that for the first torsionally excited state (the vt = 1 torsional state) is reported. In the present study, 371 A-species transitions up to J = 46 and Ka = 7 and 317 E-species transitions up to J = 33 and Ka = 7 in the vt = 1 torsional state were newly assigned. The transition frequency data were least-squares-analyzed by using the pseudo-principal axis method (PAM) Hamiltonian to determine 31 parameters consisting of rotational, centrifugal distortion, and internal-rotational constants.

A tritium enhanced water absorption spectrum previously recorded in the 7200-7245 cm region is analysed. Variational calculations for HTO predict absorption to be dominated by the 2ν vibrational band in this region. New assignment are made for HTO based on this line list with a band origin measured to be at 7236.03 cm. A calculated TO line list predicts absorption in this region to be below the experimental detection limit despite the large quantity of tritium present. From 170 lines observed 37 known H O lines are identified and 111 new HTO assignments are made. © 2013 Elsevier Ltd. All rights reserved.

The trans -ethyl methyl ether molecule has three low-lying torsional modes, that is, two inequivalent methyl internal rotations and an asymmetric skeletal torsion. The internal rotations of the CCH 3 and OCH 3 methyl rotors and the skeletal torsion correspond to the vibrational modes, ν 28 , ν 29 and ν 30 respectively. In this study, the microwave absorption spectrum in the ν 28 = 1 CCH 3 torsional state was analyzed for the first time. Nine hundred fifty seven lines up to J = 48 and K = 4 were assigned, and the rotational, centrifugal distortion and internal rotational tunneling parameters were determined with the use of a tunneling matrix formalism. By combining the present results on the ν 28 = 1 torsional state with those for the ν 30 = 1 skeletal torsional state and the ν 29 = 1 OCH 3 torsional state, torsional couplings are estimated in order to understand quantitatively the inverted A/E sequence patterns observed for those three excited torsional states.

We report the structure-activity relationship of a series of coumarins as aldose reductase 2 (ALR2) inhibitors and their suppressive effect on the accumulation of galactitol in the rat lens. We evaluated their ALR2 selectivity profile against sorbitol dehydrogenase and aldehyde reductase (ALR1). Our study revealed that substitutions in the C7 OH group enhanced the potency toward ALR2, while the C6 OH group interferes with ALR1 inhibition activity. Having the phenyl moiety at C4 leads to improved potency and improved selectivity. A molecular docking study suggested that 6,7-dihydroxy-4-phenylcoumarin (15) binds to ALR2 in a different manner from epalrestat. Furthermore, compound 15 clearly suppressed galactitol accumulation in a dose-dependent manner. These results provide an insight into the structural requirements of coumarins for developing a new-type of selective ALR2 inhibitor.

The trans-ethyl methyl ether molecule has two inequivalent methyl group internal rotors. One methyl rotor is bonded to the oxygen atom and the other to the carbon atom. The internal rotations of these methyl rotors correspond to the vibrational modes, ν 29 and ν 28 , respectively. In this study, the microwave absorption spectrum in the ν 29 = 1 excited torsional state was analyzed for the first time. Initial assignment has been carried out by making use of measurements at dry ice temperature. Over 1500 lines up to J = 76 and K = 5 were assigned. The spectrum involving internal rotation splittings was analyzed by using the tunneling matrix formulation developed by Hougen.

The microwave spectrum of the trans -ethyl methyl ether in the skeletal torsionally excited state was analyzed for the first time. The trans -ethyl methyl ether molecule has two inequivalent methyl group internal rotors but the only splitting due to the methyl group connected to the oxygen was observed. The measurement at the dry ice temperature helped the assignment of the spectrum. Over 1100 transitions up to J = 91 and K = 6 were assigned. The analysis of the spectra was carried out based on Hougen’s tunneling matrix formulation.

We consider multi-class priority queues with nonpreemptive services controlled by an exponential timer and multiple vacations. By reducing this model to the priority model with Bernoulli schedule analyzed by Katayama (1997), we obtain the Laplace-Stieltjes transform for the sojourn time in the system for each priority class, assuming (i) constant service times or (ii) general service times with either 1-limited or exhaustive service, and provide recursive equations to evaluate its first two moments.

Emission and excitation spectra of the 3s 2 1 S 0 –3s3p 1 P 1 transition of Mg atom in pressurized liquid helium-4 and helium-3 have been measured. In the emission spectra we have found that their transition wavelengths, which are significantly red shifted, remain constant or slightly increase with increasing the liquid helium pressure, whereas for other alkali–earth atoms the increase of the liquid pressure always shifts their emission spectra toward shorter wavelength. Our theoretical calculations based on a bubble model have successfully reproduced this unique spectral property, and have suggested the possibility of the formation of a Mg(3s3p 1 P 1 )He n exciplex in a bubble.

We consider a cyclic-service queueing system (polling system) with time-limited service, in which the length of a service period for each queue is controlled by a timer, i.e., the server serves customers until the timer expires or the queue becomes empty, whichever occurs first, and then proceeds to the next queue. The customer whose service is interrupted due to the timer expiration is attended according to the nonpreemptive service discipline. For the cyclic-service system with structured batch Poisson arrivals (Mx/G/1) and an exponential timer, we derive a pseudoconservation law and an exact mean waiting time formula for the symmetric system.

Infrared spectra in the region of the CN stretchings of aqueous KOCN-KSCN binary systems as well as KOCN or KSCN pure solutions are observed in the gel phase of the mono-palmitin-water system, where two-dimensional water layers are formed. Similar observations are carried out for the systems with sodium dodecyl sulphate (SDS). The spectra are analyzed on the basis of a linear response function with mechanical and damping coupling constants. In the KOCN or KSCN pure solutions the band widths depend slightly on SDS and differ considerably with those in the isotropic solutions, clarifying the difference in the correlation time of water between the two-dimensional and the isotropic systems. In the KOCN–KSCN binary systems the relative intensities of the OCN − with SCN − ions depend considerably on SDS. This is explained in terms of the orientation of OCN − ions, which prefer to orient parallel to the water-lipid boundary. The mechanical coupling constant is somewhat larger than that expected from two-dimensional layers. This results in the effects of both the reduction of a dielectric constant of water and multiple reflections of an electric field on the water-lipid boundary.

Recent studies indicate a key role of Mitf (microphthalmia-associated transcription factor) in the differentiation of the retinal pigment epithelium (RPE). To explore transdifferentiation processes, we used small interfering RNA (siRNA) targeting Mitf. Transfection of embryonic chick RPE cells with a non-silencing fluorescein-labelled control siRNA demonstrated a high (84%) transfection efficiency. Transfection of Mitf siRNA reduced Mitf synthesis at the mRNA and protein levels as analysed by real-time RT-PCR and Western blot. Mitf siRNA suppressed the expression of Mitf RNA to 25.0% of the level in control cells (P

Infrared spectra in the region of the CN stretching of aqueous KOCN–KSCN binary systems were observed in order to investigate the vibrational coupling between two oscillators. Additivity in infrared intensities was not found by analyzing each band separately. On the contrary, the additivity was largely obtained from analysis through the use of the linear response function including the complex coupling term. The increase of band widths from the pure solutions to the binary systems is explained in terms of damping coupling. These results reveal that the line shape of the binary systems arises from the dynamic coupling process interacting with electromagnetic waves. The mechanical coupling constant is discussed on the basis of the oscillating dipole–dipole interactions.

We consider an M/G/1-type, two-phase queueing system, in which the two phases in series are attended alternatively and exhaustively by a moving single-server according to a batch-service in the first phase and an individual service in the second phase. We show that the two-phase queueing system reduces to a new type of single-vacation model with non-exhaustive service. Using a double transform for the joint distribution of the queue length in each phase and the remaining service time, we derive Laplace-Stieltjes transforms for the sojourn time in each phase and the total sojourn time in the system. Furthermore, we provide the moment formula of sojourn times and numerical examples of an approximate density function of the total sojourn time.

The rotationally resolved A (010)– X (000) spectrum of DCCl between 12 880 and 12 964 cm −1 was measured using frequency-modulated laser absorption spectroscopy of jet-cooled and ambient temperature samples. Transitions to levels with K a ′=0 and 1 were assigned, and their analysis leads to improved accuracy of both the ground state rotational constants of DCCl and, when combined with existing data for HCCl, the geometry of the radical. In addition to the expected perpendicular band structure, a number of parallel (Δ K a =0) subbands were observed. Their intensity derives from a combination of c -type Coriolis coupling and axis-switching (J. T. Hougen and J. K. G. Watson, 1965, Can. J. Phys. 43, 298) resulting from the change in geometry between the two states. The two contributions have been calculated for the (010)–(000) band of DCCl and previously recorded data for HCCl. Satisfactory agreement with experimental measurements was obtained. The Coriolis contributions are small for these transitions, but may add to or subtract from the axis-switching. For higher bending excitation in the upper state, Coriolis coupling is predicted to make larger contributions to the parallel subband intensities.

The (0,0) and (1,0) bands of the E 3 Π– X 3 Δ transition of TiO in the near-infrared have been recorded by frequency modulated laser absorption spectroscopy in a laser ablation/free jet expansion source. The observed linewidths (FWHM) varied from 300 to 500 MHz according to the expansion conditions and are dominated by residual Doppler broadening in the unskimmed source. Data for the (0,0) band have been obtained for TiO molecules containing all the naturally occurring Ti isotopes but, for the weaker (1,0) band, only for 48 TiO. Rotational constants for the two upper state vibrational levels were derived by fitting the data to an effective Hamiltonian; equilibrium parameters have been calculated. The experimental results are compared to the results of ab initio calculations on the E – X system. Ab initio results for the b – a system and for the lowest 3 Σ − state are also presented. They indicate that the D 3 Σ − state is not a very low-lying state.

This paper considers a new type of priority queues with semiexhaustive service and setup times, which operates as follows. A single server continues serving class-n messages in queue n until the number of messages decreases to one less than that found upon the server's last arrival at queue n, where 1 @? n @? N. In succession, messages of the highest class present in the system, if any, will be served according to this semiexhaustive service. Two types of class-dependent setup times are considered: Setup Time I (the first service after a setup time is given to the first arrival during an idle period) and Setup Time II (the first service after a setup time is given to the highest class message in the system at the end of the setup time). We derive the Laplace-Stieltjes transforms of the message waiting times for each kind of setup times and explicit formulae for the mean waiting times. We also give some numerical results to assess the influence of setup times.

Retinal pigment epithelium (RPE) has essential roles that maintain functions of the neural retina. Previously, we described that the 3b5 monoclonal antibody (3b5 mAb) recognized the RPE cells in the chick embryonic eye. In the present study, a gene coding for the 3b5 antigen has been cloned and sequenced. A 10-day-old embryonic RPE cDNA library was constructed in lambda Uni-ZAP XR, and screened with the 3b5 mAb as a probe. The complete nucleotide sequence of the antigen recognized by the 3b5 mAb was obtained. The cDNA encodes a 735 amino acid protein with a calculated molecular mass of 80,147 Da. The deduced amino acid sequence shares 72% identity with the human 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) type IV. Northern blot analysis detected a 2.9 kb transcript. Immunohistochemical and in-situ hybridization studies revealed that 17 beta-HSD type IV was preferentially expressed in the RPE cells. The expression of steroid metabolizing enzymes in the RPE cells is able to create estrogenic environment, which may have a role of maintenance of the neural retina.

Astrocytes exhibit a diverse morphology and numerous functions in the central nervous system as well as in the retina. In order to obtain markers for the analysis of astrocytes, we prepared monoclonal antibodies that recognized antigens specific to astrocytes. Monoclonal antibody (mAb), designated KK1, reacted with the processes of astrocytes in the nerve fiber layer and the ganglion cell layer in the human retina as detected by indirect immunofluorescence. Normal Müller cells, whose processes are localized vertically in retina, were not labeled by KK1 mAb. In mouse brain, KK1 mAb reacted specifically with astrocytes in the white matter, but not with those in the gray matter. Studies employing a high-resolution confocal laser scanning microscope and double-labeling with KK1 mAb and commercially available anti-glial fibrillary acidic protein (GFAP) mAb (GA5) revealed that KK1 mAb visualized the processes that were not recognized by anti-GFAP mAb (GA5) in both human retina and mouse brain. In cultured mouse astrocytes, KK1 mAb reacted only with anti-GFAP mAb (GA5)-positive cells, but a small percentage of anti-GFAP mAb (GA5)-positive cells were labeled with KK1 mAb. In addition, the subcellular distribution of the KK1 antigen in cultured astrocytes apparently differed from that of GFAP labeled by anti-GFAP mAb (GA5). The antigen that was purified from the normal mouse brain by KK1 mAb-conjugated beads reacted with anti-GFAP mAb(GA5) in immunoblotting. No reactivity of KK1 mAb was observed in immunohistochemical analysis in GFAP -/- mutant mouse brain. These results demonstrate that KK1 mAb specifically recognized an epitope of GFAP that did not react with other anti-GFAP mAb (GA5). Retinal astrocytes and a subtype of astrocytes in the white matter of mouse brain shared the epitope that was recognized by KK1 mAb. KK1 mAb might be a powerful tool to investigate a subtype of astrocytes.

A sojourn time analysis is provided for a cyclic-service tandem queue with general decrementing service which operates as follows: starting once a service of queue 1 in the first stage, a single server continues serving messages in queue 1 until either queue 1 becomes empty, or the number of messages decreases to k less than that found upon the server's last arrival at queue 1, whichever occurs first, where 1 @? k @? ~. After service completion in queue 1, the server switches over to queue 2 in the second stage and serves all messages in queue 2 until it becomes empty. It is assumed that an arrival stream is Poissonian, message service times at each stage are generally distributed and switch-over times are zero. This paper analyzes joint queue-length distributions and message sojourn time distributions.